CN102206409B - Hydrogel forming covalent cross-linking rapidly under mild conditions and preparation method thereof - Google Patents

Abstract

The invention discloses a hydrogel forming covalent cross-linking rapidly under mild conditions and a preparation method thereof. The hydrogel contains two components, i.e. NHS (N-Hydroxy Succinimide) ester of PEG (Polyethylene Glycol) and PEG containing N-terminal group cysteine. The two components are dissolved and mixed to obtain the hydrogel. The hydrogel disclosed by the invention can form covalent cross-linking rapidly under mild conditions, and is particularly suitable for being manufactured into surgical sealants.

Description

A hydrogel rapidly forming covalently cross-linked under mild conditions and its preparation method

technical field

The invention relates to a hydrogel and a preparation method thereof, in particular to a hydrogel capable of rapidly forming covalent crosslinks under mild conditions and a preparation method thereof.

Background technique

Hydrogel (Hydrogel) is a hydrophilic polymer network structure, insoluble in water, but can absorb and retain a large amount of water, highly swellable in aqueous solution, and has good biocompatibility and similarity. They can be used in surgical sealants and adhesives, drug release, tissue repair and tissue engineering in the field of medicine and biology.

Existing hydrogel systems are usually formed through chemical or physical actions. Chemical crosslinking to form aqueous gels often involves the use of toxic crosslinking agents and free radicals, and the resulting hydrogels are usually not biodegradable. On the other hand, physical hydrogels are formed through non-covalent interactions, such as hydrogen bonds, ionic interactions, hydrophobic interactions, and phase transitions. The physical hydrogel thus formed is relatively fragile. Therefore, it remains a challenge to form covalently cross-linked hydrogels under mild conditions without the use of toxic reagents to meet clinical needs.

Hydrogels have been used clinically as surgical sealants. As an auxiliary means of surgical operations, surgical sealants are used for hemostasis, anti-sticking and plugging in surgical operations, and are widely used in brain surgery, cardiac surgery, thoracic and abdominal surgery, neurosurgery and other operations.

At present, surgical sealant products using hydrogels can be divided into three categories: one is fibrinogen extracted from mammalian blood (cow blood, pig blood, or human blood) Surgical sealant, or a sealant composed of bovine gelatin protein. Fibrinogen (fibrinogen) extracted from mammalian blood is catalyzed by thrombin (thrombin) extracted from mammalian blood to form a polymer fibrin (fibrin) gel, such as Tisseel™, An It can be glued and embroidered. FloSeal™ uses bovine gelatin and thrombin. Such products are products derived from blood, and there is a risk of being contaminated by pathogenic organisms, for example, there may be viruses and pathogenic sources that cause AIDS, hepatitis B, mad cow disease, swine flu and other diseases. In addition, proteins from porcine and bovine sources and thrombin are heterologous proteins used in humans with potentially disastrous immune responses.

Another type of surgical sealant product is to use animal-derived proteins to cross-link under the action of small molecule aldehyde cross-linkers to form hydrogels, for example, use adipaldehyde and bovine-derived gelatin proteins to form hydrogels. US Pat. No. 5,385,606 describes a method for cross-linking hydrogels using bovine blood-derived albumin and adipaldehyde. In addition to the risk of contamination by pathogenic organisms in animals and allergies to foreign proteins, this type of hydrogel also has a certain degree of toxicity in the use of small molecule aldehyde crosslinkers.

The third type of surgical sealant products are all composed of artificially synthesized biocompatible polymer biomaterials. Such products have no risk of contamination by pathogenic organisms and allergies to foreign proteins.

US 5410016 describes the use of polyethylene glycol and polylactic acid to prepare linear block copolymers, and then at both ends of the molecule through ester linkages to link acrylic acid moieties that can be polymerized and cross-linked under light excitation. The aqueous solution of the block copolymer containing acrylate at both ends of the molecule quickly forms a hydrogel (FocalSeal ^® ) in situ under the catalyst and light after being applied to the application site. The disadvantage of this FocalSeal ^® hydrogel system as a surgical sealant is that it is somewhat difficult to handle in practice.

US 6566406 discloses a hydrogel composed of two solutions: a solution of activated acid derivatives of four-branched polyethylene glycol mixed with a solution of a short peptide trilysine (Lys-Lys-Lys) Surgical sealant formed by post-in situ polymerization. This in situ formed hydrogel system needs the pH value of the solution to be around 9.5 in order to form a hydrogel rapidly. Under such alkaline conditions, it is easy to produce effects on local irritation and inflammatory reactions.

US 6312725 discloses a hydrogel surgical sealant product (CoSeal ^® ) formed in situ by mixing two solutions. The two solutions are a solution of tetra-branched polyethylene glycol terminated with an activated acid derivative and a solution of tetra-branched polyethylene glycol terminated with a mercapto group, which are mixed and then polymerized in situ by the formation of a thioester Hydrogels. The disadvantage of this hydrogel CoSeal ^® is that it needs the pH value of the solution to be 9.6 to quickly form the hydrogel, and it also has local irritation and inflammation. And unstable, the hydrogel formed by the cross-linking of thioester bonds has poor stability and a short time to play a role.

Thioester compounds and N -terminal cysteine compounds form a new amide bond after mixing under mild conditions (phosphate buffered saline, pH 7-8). This chemical reaction is called natural chemical linkage. WO2008/131325 describes the formation of hydrogels using natural chemical linkages as cross-linking reactions. A solution of tetra-branched polyethylene glycol terminated with thioester and a solution of tetra-branched polyethylene glycol terminated with cysteine were used. These two solutions polymerize in situ under mild conditions (pH 7–8) to form hydrogels by forming amide bonds. As a method of covalent cross-linking of hydrogels, natural chemical linkage has several obvious advantages: ① Chemoselective, sulfolipids can only bind to compounds containing cysteamine (cysteamine) structure, or N -terminal cysteine The compound reacts to form a new amide bond without interference from the presence of other thiols and thiols; ②under mild conditions, it reacts efficiently without using catalysts, initiators and other potentially toxic compounds; ③reacts with other chemical linkages using thiols The formed hydrogel is different, and the natural chemical ligation reaction forms a new amide bond while also generating a sulfhydryl group on the backbone, so that the formed hydrogel has better bioadhesion. However, since the two solutions disclosed in WO2008/131325 form a hydrogel slowly (about 3 minutes) after mixing, they are not suitable as a surgical sealant.

Contents of the invention

The object of the present invention is to provide a novel hydrogel.

The technical scheme that the present invention takes is:

A hydrogel, containing two components A and B, the structural formula of component A is shown in general formula I

The structural formula of component B is shown in general formula Ⅱ

In the formula, Y is a linking atom or a linking group, X is a molecular nucleus with carbon or branch number not less than 2, n is an integer between 0 and 200, and m is an integer between 2 and 32.

Preferably, the structural formula of component B is shown in general formula III

In the formula, R = -H, -CH ₂ CH ₂ COOH or -(CH ₂ ) ₃ NH(NH)CNH ₂ , Y is a linking atom or a linking group, X is a carbon or a molecule with no less than 2 branches For the mother core, n is an integer between 0 and 200, and m is an integer between 2 and 32.

Preferably, n is an integer between 50 and 70. In particular, n=57.

Preferably, m is an integer between 4-16. In particular, m=4, X is C.

The linking atom is O, N or C.

The preparation method of above-mentioned hydrogel comprises the following steps:

1) Dissolve components A and B in a solution with a pH of 7 to 8 to obtain a mixed solution of components A and B respectively;

2) Mix the mixed solutions of components A and B to obtain a hydrogel.

Preferably, the mass volume concentration of the mixed solution of components A and B is 5%-20%.

Preferably, components A and B are mixed in a molar ratio of 4:1 to 1:4.

Preferably, the solution with a pH of 7-8 is a sodium phosphate buffer.

In the hydrogel of the present invention, after the aqueous solutions of components A and B are mixed, a new amide bond can be quickly reacted under mild conditions, and a covalently cross-linked hydrogel can be obtained after mixing in less than 10 seconds. The hydrogel of the invention has a stable structure and excellent viscoelasticity, and can be used as a surgical sealant.

Description of drawings

Figure 1 and Figure 2 are rheological behavior diagrams of the hydrogel of the present invention.

Detailed ways

A hydrogel, containing two components A and B, the structural formula of component A is shown in general formula I

The structural formula of component B is shown in general formula Ⅱ

In the formula, Y is a linking atom or a linking group, X is a molecular nucleus with carbon or branch number not less than 2, n is an integer between 0 and 200, and m is an integer between 2 and 32.

Preferably, the structural formula of component B is shown in general formula III

In the formula, R = -H, -CH ₂ CH ₂ COOH or -(CH ₂ ) ₃ NH(NH)CNH ₂ , Y is a linking atom or a linking group, X is a carbon or a molecule with no less than 2 branches For the mother core, n is an integer between 0 and 200, and m is an integer between 2 and 32. Of course, according to the basic common sense of those skilled in the art, the number n of repeating units of PEG can be different in order to meet different requirements. The number of branches of the multi-branched molecular core is at least 2, preferably at least 3, so that a living cross-linking reaction can occur between components A and B to form a three-dimensional network. To achieve the purpose of forming hydrogel. These multi-branched molecular cores may be commonly used molecular cores in the art. When the hydrogel of the present invention is used in the human body, the molecular cores are preferably those that can be degraded in the body and have no toxic effect on the human body.

Preferably, n is an integer between 50 and 70. In particular, n=57.

Preferably, m is an integer between 4-16. In particular, m=4, X is C. In this case, each branch can form a hydrogel more uniformly.

The linking atom is O, N or C. Of course, other divalent linking groups that can be degraded in the body and have no toxic effect on the human body can also be used. The choice of these groups is a routine choice of those skilled in the art.

The preparation method of above-mentioned hydrogel comprises the following steps:

1) Dissolve components A and B in a solution with a pH of 7 to 8 to obtain a mixed solution of components A and B respectively;

2) Mix the mixed solutions of components A and B to obtain a hydrogel.

Preferably, the mass volume concentration of the mixed solution of components A and B is 5%-20%.

Preferably, components A and B are mixed in a molar ratio of 4:1 to 1:4.

Preferably, the solution with a pH of 7-8 is a sodium phosphate buffer. Of course, other buffers can also be used.

Below in conjunction with embodiment, further illustrate the present invention.

Component A Synthesis

The reaction equation is as follows:

PEG4A-SA Synthesis:

Take 80 mg of succinic anhydride (molecular weight: 100, 0.8 mmol) and 1 g of four-branched polyethylene glycol PEG4A (average molecular weight: 10k, amino group: 0.4 mmol), add 2 ml of dichloromethane to dissolve, stir overnight, detect Reaction solution, ninhydrin reaction was negative (yellow);

Dry the solvent with nitrogen, add 50 ml of methanol to dissolve all solids, freeze the solution overnight (-20°C), take it out and centrifuge (-9°C, 6000rpm, 20 minutes), and remove the supernatant. Repeat the above process of dissolving in methanol, freezing, centrifuging, and removing the supernatant for the precipitate three times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat the above purification After two processes, vacuum-dried for two days to obtain PEG4A-SA.

¹ HNMR (CDCl ₃ , 500MHz) δ 3.2-3.8 (m, -O-CH ₂ -CH ₂ -O-), 2.61 (2H, t, J = 7 Hz, -NH-CO- CH ₂ -), 2.48 (2H, t, J = 7 Hz, -CH2 _- COOH).

components A ( PEG4A-SA-Osu )Synthesis:

Take PEG4A-SA (0.4mmol), 0.115 g (1 mmol) of N -hydroxysuccinimide (HOSu), dissolve in 1 ml of acetonitrile, add 206 mg (1 mmol) of DCC/1 ml of dichloromethane, shake overnight, and filter Remove the solid precipitate, evaporate the filtrate to dryness under reduced pressure, add 50ml of isopropanol to dissolve the residue, freeze the solution overnight (-20°C), take it out and centrifuge (-9°C, 6000rpm, 20 minutes), remove the supernatant;

Repeat the purification process of dissolving in isopropanol, freezing, centrifuging and removing the supernatant for 3 times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat After the above purification process twice, it was vacuum-dried for two days.

¹ HNMR (CDCl ₃ , 500MHz) δ 3.3-3.8 (m, -O-CH ₂ -CH ₂ -O-), 2.95 (2H, t, J = 7 Hz, -NH-CO- CH ₂ -), 2.80 (4H, s, -N-CO- CH2 - _CH2 - _CO -N-), 2.57 (2H, t, J = 7 Hz, -CH2 - _CO -ON-).

Of course, other known methods can also be used, eg, to make the A component.

Component B Synthesis:

Component B can be removed by reacting a protected cysteine, such as Boc-Cys(Trt)-OH, or L-thioproline, with a polymer containing amino groups, hydroxyl groups, or those that can be converted to The protecting group reaction is obtained.

For example, when using 4-branched polyethylene glycol (PEG4A) with an amino terminal group as the polymer nucleus, directly react with Boc-Cys(Trt)-OH, and then remove the protecting group to obtain component B. Its reaction equation is as follows:

Component B can also be obtained by fully protected cysteine-containing dipeptides, such as Boc-Cys(Trt)-Gly-OH, Boc-Cys(Trt)-Glu(OtBu)-OH and Boc-Cys(Trt) -Arg(Pbf)-OH, obtained by reacting with polymers containing amino groups, hydroxyl groups, or those that can be converted into these functional groups, and removing the protecting group.

Fully protected cysteine-containing dipeptides can be obtained by solid-phase synthesis of Fmoc polypeptides. Its reaction equation is as follows:

For example, when using 4-branched polyethylene glycol (PEG4A) with an amino terminal group as the polymer core, react directly with a fully protected dipeptide containing cysteine, and remove the protecting group to obtain the component b. Its reaction equation is as follows.

B1 ( Cys-PEG4A )Synthesis

Take Boc-Cys(Trt)-OH (0.25 mmol), PEG4A (0.5g, amino 0.2 mmol), BOP (0.11g, 0.25 mmol) were dissolved in dichloromethane (2ml), then, DIEA (44 μl, 0.25 mmol) was added, shaken for 2 hours, and the solvent was blown dry with nitrogen;

Add 50 ml of methanol to dissolve all solids, freeze the solution overnight (-20°C), take it out and centrifuge (-9°C, 6000rpm, 20 minutes), and remove the supernatant;

Repeat the above process of dissolving in methanol, freezing, centrifuging, and removing the supernatant for the precipitate three times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat the above purification After two processes, vacuum-dried for two days to obtain Boc-Cys(Trt)-PEG4A.

Silica gel thin-layer chromatography (solvent system DCM-MeOH-HOAC = 100:3:1) detected that there was no Boc-Cys(Trt)-OH. Ninhydrin test showed pale yellow. ¹ HNMR (CDCl ₃ , 500MHz) δ 7.40-7.26 (15H, m, -CPh ₃ ), 3.8-3.4 (m, -O-CH ₂ -CH ₂ -O-), 1.41 (9H, s, t-Bu ).

Add triisopropylsilane (TIS) 1 ml and 1,2-dimercaptoethane (EDT) 1 ml trifluoroacetic acid (30 ml) to the dried Boc-Cys(Trt)-PEG4A sample, room temperature After stirring for 2 hours, the solvent was removed under reduced pressure;

Dissolve the residue with methanol (50ml), freeze the methanol solution overnight (-20°C), take it out and centrifuge (-9°C, 6000rpm, 20 minutes), remove the supernatant;

Repeat the above process of dissolving in methanol, freezing, centrifuging, and removing the supernatant for the precipitate three times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat the above purification After the 2nd process, it was vacuum dried for two days to obtain the trifluoroacetic acid salt of component B1 ( Cys-PEG4A ).

Ninhydrin test was dark blue. Ellman's reagent reaction was bright yellow. Indicates that the protecting group has been removed. The trifluoroacetic acid salt was dissolved in ammonium bicarbonate solution (0.1 M, 25 ml), and lyophilized to obtain fraction B1 ( Cys-PEG4A ).

Synthesis of protected cysteine dipeptides

The synthesis of Boc-Cys(Trt)-Gly-OH, or Boc-Cys(Trt)-Glu(OBu)-OH, or Boc-Cys(Trt)-Arg(Pbf)-OH uses the peptide solid-phase synthesis method, Fmoc Chemistry and 2-chlorotrityl chloride resin. Proceed as follows:

Take the resin (1g, 1.55mmol/g), add Fmoc protected amino acid, Fmoc-Gly-OH, or Fmoc-Glu(OBu)-OH, or Fmoc-Arg(Pbf)-OH in dichloromethane solution (1mmol , 10ml), add diisopropylethylamine (DIEA) (1ml), after shaking for 30 minutes, wash the resin three times with dimethylformamide (DMF);

Add 20ml of DCM-MeOH-DIEA (8:1:1), shake for 20 minutes, and wash the resin three times with dimethylformamide (DMF). Add 20 ml of 20% hexahydropyridine in dimethylformamide solution, shake for 20 minutes, remove the solvent, wash the resin four times with dimethylformamide (DMF), and the ninhydrin test shows dark blue;

Take Boc-Cys(Trt)-OH (0.92 g, 2 mmol), BOP (0.88 g, 2 mmol), dissolved in 8 ml of dichloromethane, then added 522 microliters (3 mmol) of DIEA, left to stand for 10 minutes, added to the resin, and shaken for 2 hours;

Wash the resin three times with dimethylformamide (DMF) and methanol respectively, dry the resin in vacuum, and the ninhydrin test shows light yellow;

Take the polypeptide resin obtained above, add 30ml of dichloromethane solution of 1% trifluoroacetic acid respectively, shake for 20 minutes, and collect the solution;

Add 30ml of 1% trifluoroacetic acid in dichloromethane repeatedly, shake for 20 minutes, collect the solution 4 times, combine the solution, add 2ml of pyridine, remove the solvent under reduced pressure, add water to precipitate the product.

The precipitate was washed with water until the eluate was neutral, and dried in vacuo to obtain the protected cysteine dipeptide.

B2 Synthesis

Take Boc-Cys(Trt)-Gly-OH, or Boc-Cys(Trt)-Glu(OBu)-OH, or Boc-Cys(Trt)-Arg(Pbf)-OH (0.25 mmol), PEG4A (0.5g , Amino 0.2 mmol), BOP (0.11g, 0.25 mmol) were dissolved in dichloromethane (2ml), then, DIEA (44 μl, 0.25 mmol) was added, shaken for 2 hours, the solvent was blown dry with nitrogen, and 50 ml of methanol was added to dissolve all Solid, freeze the solution overnight (-20°C), remove and centrifuge (-9°C, 6000rpm, 20 minutes), remove the supernatant. Repeat the above process of dissolving in methanol, freezing, centrifuging, and removing the supernatant for the precipitate three times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat the above purification After 2 times, vacuum dry for two days to get Boc-Cys(Trt)-Gly-PEG4A, or Boc-Cys(Trt)-Glu-PEG4A, or Boc-Cys(Trt)-Arg(Pbf)-PEG4A, silica gel Thin-layer chromatography (solvent system DCM-MeOH-HOAC = 100:3:1) detects the presence of unprotected dipeptide, ninhydrin test shows light yellow, and H-NMR spectrum confirms its structure;

Add trifluoroacetic acid (30 mL), containing 1 mL of triisopropylsilane (TIS) and 1 mL of 1,2-dimercaptoethane (EDT), stirred at room temperature for 2 hours, and removed the solvent under reduced pressure;

Dissolve the residue with methanol (50ml), freeze the methanol solution overnight (-20°C), take it out and centrifuge (-9°C, 6000rpm, 20 minutes), remove the supernatant;

Repeat the above process of dissolving in methanol, freezing, centrifuging, and removing the supernatant for the precipitate three times, then add 50 ml of ether, shake for 10 minutes, centrifuge (20°C, 6000rpm, 20 minutes, remove the supernatant, repeat the above purification After the process twice, it was vacuum dried for two days to obtain the trifluoroacetic acid salt of component B2 (B-Gly, B-Glu or B-Arg).

Ninhydrin test was dark blue. Ellman's reagent reaction was bright yellow. Indicates that the protecting group has been removed.

The trifluoroacetate salt of component B2 was dissolved in ammonium bicarbonate solution (0.1 M, 25 ml), and the product B2 was obtained after lyophilization.

Hydrogel Formation and Preparation

Take a test tube (100 mm length × 13 mm diameter), put a stirring bar (10 mm length ×3 mm diameter) into the test tube, control the temperature at 37°C, adjust the stirring speed to 2000 rpm, add 250 μl of component B1 or component B2 sodium phosphate buffer solution (0.1 M, pH 7.2) (20% w/v), continue stirring, then add 250 μl of component A in sodium phosphate buffer (0.1 M, pH 7.2) (20% w/v),.

Take Comparative Example 1, Comparative Example 2, and Comparative Example 3 (the hydrogel products disclosed in US6566406, US6312725 and WO2008/131325, respectively), and conduct tests at the same concentration and under the same conditions.

After mixing, start timing with a chronograph. When the stirring bar in the solution stops rotating, stop timing and record the time, that is, the formation time of the hydrogel. The results are shown in the table below.

Component B1 of the present invention can form a hydrogel formed by cross-linking disulfide bonds through sulfhydryl groups, but the speed is very slow.

Although the method for judging the formation time of the above-mentioned hydrogel is relatively rough, it may destroy the formed network structure due to the rotation of the stirring bar, so that the recorded time is longer than the formation time of the real hydrogel. However, as long as the test is carried out under the same controlled conditions, the measured time should be of relative reference value.

Hydrogel dissolution experiment: ①Mix the sodium phosphate buffer solution of component A (0.1 M, pH 7.2) (10%) and the sodium phosphate buffer solution of component B (0.1 M, pH 7.2) (10%) %), measure two parts of 100 microliters into two plastic vials, check after 10 minutes, it is a hydrogel, add 100 microliters of 0.1M into the two small tubes Hydroxylamine aqueous solution, 100 microliters 200 mM 2-mercaptoethanol solution, shaking, the hydrogel is not dissolved;

② Take two 100 μl 10% sodium phosphate buffer solution of component B (0.1 M, pH 7.2) Separately put into two small plastic tubes. After 5 hours, they are still in solution. Over night, they are hydrogels. Treat with the above two solutions respectively, and the hydrogels are all in solution.

The results show that the hydrogel provided by the invention is not cross-linked by thioester bonds, nor is it formed by cross-links by disulfide bonds.

Rheological Behavior of Hydrogels

Hydrogel Formation Experiment:

Explanation: Because component A and component B form hydrogel rapidly under the above gel formation conditions (20%, 37°C). Under such conditions, the gel formation time cannot be measured and there is not enough operating time on the rheometer. Therefore, in rheological experiments, lower polymer concentrations and reaction temperatures (5%, 20°C ) to slow down the hydrogel formation rate and prolong the gel formation time, so as to study the rheological behavior.

Mix an equal molar and equal volume of component A in sodium phosphate buffer (0.1 M, pH 7.2) (5% w/v) and component B1 in sodium phosphate buffer (0.1 M, pH 7.2) (5% w/v), measure 500 microliters of the solution, quickly add the solution to the temperature-controlled sample plate (20°C), adjust the position of the plate (25 mm in diameter) so that the solution fills the 1 mm gap between the plates.

Install the humidity control equipment, and measure the storage modulus (G') and loss modulus (G") under the condition of constant strain (strain) 1% and frequency (frequency) 1 Hz, oscillatory mode (oscillatory mode). A data point is collected every 15 seconds. The longest measurement time is 300 minutes.

Frequency sweep experiment: After G' reached a stable plateau value, a frequency sweep (0.01 Hz to 10 Hz) was performed under constant strain (1%).

Tension sweep experiment: Under a constant frequency (1Hz), a strain sweep (1% to 100%) was performed.

The test results are shown in Figures 1 and 2.

data analysis

In hydrogel formation experiments, the intersection of G' and G" is called the hydrogel formation point, and the corresponding time point is the hydrogel formation time. In tension and frequency sweep experiments, stable G' values indicate the formation of The hydrogel is a covalently crosslinked hydrogel. As can be seen from the figure, the hydrogel of the present invention has a very short formation time, is a covalently crosslinked hydrogel, and has excellent viscoelasticity.

The cross-linking mechanism of hydrogel of the present invention is as follows:

Through this reaction, after the aqueous solutions of components A and B of the present invention are mixed, a hydrogel can be rapidly formed. According to this response, those skilled in the art can easily know that components A and B are preferably mixed in a molar ratio of 1:1. Of course, other molar ratios can also be used according to specific needs, such as A:B =4:1～1:4, such as 0.25:1, 0.5:1, 0.75:1, 1:1, 1.25:1, 1.5:1, 1.75:1, 2:1.

According to the different components, the hydrogel shown in the following structural formula can be obtained respectively.

Of course, if other molecular cores are used, the structure will be slightly different, but covalent cross-linking can also occur to obtain the corresponding hydrogel. Its structure is readily available to those skilled in the art.

Claims (10)

1. A kind of hydrogel, its raw material contains A, B two kinds of components, and the structural formula of A component is as shown in general formula I The structural formula of component B is shown in general formula Ⅱ In the formula, Y is a connecting atom or a connecting group, X is a molecular nucleus with carbon or branch number not less than 2, n in the general formula I is an integer between 50 and 200, and n in the general formula II is An integer between 0 and 200; m in general formula I is an integer between 2 and 32, m in general formula II is an integer between 4 and 32, or m in general formula I is between 4 and 32 Integer between, m in general formula II is an integer between 2 and 32. 2. A kind of hydrogel according to claim 1, characterized in that: the structural formula of component B is as shown in general formula III

In the formula, R = -H, -CH ₂ CH ₂ COOH or -(CH ₂ ) ₃ NH(NH)CNH ₂ , Y is a linking atom or a linking group, X is a carbon or a molecule with no less than 2 branches For the mother core, n is an integer between 0 and 200, and m is an integer between 2 and 32. 3. A hydrogel according to claim 1 or 2, characterized in that n is an integer between 50 and 70. 4. A hydrogel according to claim 1 or 2, characterized in that m is an integer between 4 and 16. 5. A kind of hydrogel according to claim 4, is characterized in that: X is C, m=4. 6. A kind of hydrogel according to claim 1 or 2, characterized in that: the linking atom is O, N or C. 7. The preparation method of the hydrogel according to any one of claims 1 to 6, comprising the following steps: Dissolve components A and B in a solution with a pH of 7 to 8 to obtain a mixed solution of components A and B respectively; Mix the mixed solutions of components A and B to obtain a hydrogel. 8 . The method for preparing the hydrogel according to claim 7 , wherein the mass volume concentration of the mixed solution of components A and B is 5% to 20%. 9. The preparation method of the hydrogel according to claim 7, characterized in that: components A and B are mixed in a molar ratio of 4:1-1:4. 10. The preparation method of the hydrogel according to claim 7, characterized in that: the solution with a pH of 7-8 is a sodium phosphate buffer.

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