CN113289052B

CN113289052B - Controllable cross-linking and degradation material and application thereof

Info

Publication number: CN113289052B
Application number: CN202110533487.XA
Authority: CN
Inventors: 吴德成; 潘正; 叶慧君
Original assignee: Southwest University of Science and Technology
Current assignee: Southwest University of Science and Technology
Priority date: 2021-05-14
Filing date: 2021-05-14
Publication date: 2023-05-26
Anticipated expiration: 2041-05-14
Also published as: CN113289052A

Abstract

The invention provides a controllable cross-linked and degradable material and application thereof. The composite hemostatic system is formed by mixing a synthetic molecule 1, a synthetic molecule 2 and hemostatic powder, wherein the synthetic molecule 1 and the synthetic molecule 2 can react with each other in water to form gel, when the composite hemostatic system is used, the water-absorbing powder can absorb a large amount of water, the defect that the gel and the powder are washed away when large-area bleeding is avoided by gel coating, and adhesion caused by direct contact of a wound and tissues is avoided. The gel has high strength and interaction capability with tissues, and the degradation time can be adjusted to be suitable for different bleeding positions and bleeding degrees.

Description

Controllable cross-linking and degradation material and application thereof

Technical Field

The invention relates to a synthetic material, in particular to a controllable crosslinked and degradable synthetic material and application thereof in a hemostatic system.

Background

For a long time, the traditional hemostatic methods such as ligation, suture, electrocoagulation, absorbable hemostatic clips and tourniquets in clinic not only increase the surgical difficulty of medical workers, but also influence the surgical field of vision to form hidden danger of medical accidents. In recent years, various materials have been developed for hemostatic seals, including hemostatic powders, hemostatic gels, hemostatic bandages and the like. For hemostatic gels, under the flushing of large blood flow, the gel is difficult to coat on the surface of the wound, which severely limits their application; for the hemostatic bandage, the hemostatic bandage cannot be suitable for wounds with irregular shapes and can not block deep wounds for hemostasis. In contrast, hemostatic powders have received attention for their ability to handle large blood flows and to cover wounds intact. The hemostatic powder can absorb blood or adsorb blood cells to form colloid after being placed on a wound, and concentrate blood cells and hemostatic factors so as to achieve the aim of hemostasis. However, the strength of the colloid formed by the hemostatic powder is not high, and the colloid is easy to break under the impact of blood flow at a wound; the hemostatic powder has no interaction with the tissues at the wound, and the hemostatic powder must be specially fixed in the using process, so that the use is inconvenient.

Disclosure of Invention

In order to solve the problems of the hemostatic powder, the invention provides a controllable crosslinked and degradable synthetic material, and the invention provides a compound hemostatic system formed by the gel formed by the controllable crosslinked and degradable synthetic material and the water-absorbing powder, wherein the compound hemostatic system can stop large-area bleeding, can interact with tissues, has adjustable degradation speed and the like.

A controllable cross-linking and degradation synthetic material is formed by mixing two molecules of polyoxyethylene polyoxypropylene segmented copolymer, polyacrylic acid and polyethylene glycol derivative, wherein the synthetic molecule 1 and the synthetic molecule 2 are connected through chemical bonds formed by chemical reaction in phosphate buffer solution to form gel, and the gel is coated on the surface of hemostatic powder to seal the hemostatic powder, prevent the hemostatic powder from being dispersed in the large-area bleeding process, strengthen the strength of the hemostatic powder and interact with tissues, and stop the blood powder from being water-absorbing substances such as commercially available hemostatic powder, natural polysaccharide, protein, collagen and the like and derivatives thereof.

The controllably crosslinked, degradable synthetic material is composed of synthetic molecule 1 and synthetic molecule 2, the synthetic molecule 1 can be any one of formula I, formula II, and formula III:

in each of the formulae, m, n, and p may be from 28 to 112, x represents the number of arms, may be from 1 to 8, and in some embodiments is x is 2, in other embodiments is 4, and in yet other embodiments is 6.

R ₁ Is any of amino, succinimidyl ester, aldehyde, sulfhydryl, alkenyl, epoxy, maleimide groups, in some embodiments, R ₁ Amino, succinimidyl ester, mercapto;

in some embodiments, the synthetic molecule 1 may be a compound represented by any one of the following formulas 1) to 3):

1) The compound is shown as a formula I, wherein m is 28-56, n is 12-23, p is 0-15 or 12, x is 4, R ₁ Is amino; or (b)

2) The compound is shown as formula IIWherein m is 28 to 112, and x is 4 to 8,R ₁ Is amino; or (b)

3) A compound of formula III, wherein m is 28-56, x is 6 or 8,R ₁ Is aldehyde or amino. In some embodiments, in the controllably crosslinked, degraded synthetic material, synthetic molecule 2 may be any of formulas IV, V, and VI:

in each formula, m, n, p may be 2 to 112, and x represents an arm number of 1 to 8, and in some embodiments 2, 4, or 6.

In some embodiments, R ₂ Amino, succinimidyl ester, aldehyde group, mercapto group, alkenyl group, epoxy group, maleimide group, preferably amino, succinimidyl ester, mercapto group;

in some embodiments, the synthetic molecule 1 and the synthetic molecule 2 are via R ₁ And R is ₂ Any two groups of the two groups are formed by chemical reaction.

In some embodiments, the synthetic molecule 2 may be a compound represented by any one of the following formulas 1) to 4):

1) As shown in formula IV, wherein m is 11-50, n is 12-112, p is 2-6, x is 4, R ₂ Amino or mercapto; or (b)

2) Wherein m is 22, x is 2, and R2 is amino; or (b)

3) As shown in formula VI, wherein m is 56, x is 4 or 6, R ₂ Is amino, succinimidyl ester; or a mercapto group.

In some embodiments, the controllably crosslinked and degradable synthetic material comprises a compound of formula II wherein m is 28-112 and x is 4-8,R, and a compound of formula IV ₁ Is amino, m is 11-50, n is 12-112, p is 2-6, x is 4, R in the compound shown in the formula IV ₂ Is amino or mercapto.

In some embodiments, the controllably crosslinked, degradable synthetic material is composed of synthetic molecule 1 and synthetic molecule 2, the mass ratio of synthetic molecule 1 to synthetic molecule 2 may be 1:0.5-2, 1:0.5-1, 1:0.5-0.9, 1:0.5, 1:0.9, 1:1, or 1:2;

in another aspect, the invention provides a composite hemostatic system formed by the controllably crosslinked and degraded synthetic material after forming a gel and hemostatic powder.

In some embodiments, the hemostatic powder may be a commercial hemostatic powder such as regenerated cellulose-based hemostatic powder, chitosan-based hemostatic powder, starch-based hemostatic powder, collagen-based hemostatic powder, zeolite-based hemostatic powder, and the like; in some embodiments, the hemostatic powder may be a Fu and Thai degradable hemostatic powder, a quick acting powder of mesitylene, a blue crown, an Alis Thai, a Ai Wei stop microfibre hemostatic collagen, quikClot, and the like, and may be readily a powder capable of absorbing water, such as a powder of polysaccharides and derivatives thereof, proteins and derivatives thereof.

In some embodiments, the hemostatic powder may also be a polysaccharide or derivative thereof may be agar, agarose, sodium alginate, cellulose, starch, hyaluronic acid, or a derivative thereof.

In some embodiments, the hemostatic powder is also a protein or derivative thereof such as collagen, gelatin, thrombin, fibrin, or a derivative thereof.

The invention further provides a preparation method of the composite hemostatic system based on the controllably crosslinked and degradable synthetic material powder and hemostatic powder, which comprises the following steps: the synthetic molecule 1 and/or the synthetic molecule 2 are prepared into a solution with a certain proportion, and then the solution is coated on the hemostatic powder, so that the composite hemostatic system based on the controllable crosslinked and degradable synthetic material gel and the hemostatic powder can be prepared.

In some embodiments, the concentration of the solution of synthetic molecule 1 may be 10 to 500mg/ml, in some embodiments 60 to 450mg/ml, in some embodiments 300mg/ml, in some embodiments 160mg/ml, in some embodiments 278mg/ml, of the solution of synthetic molecule 1;

in some embodiments, the concentration of the synthetic molecule 2 may be 30 to 800mg/ml, specifically 70 to 500mg/ml, in some embodiments 40 to 450mg/ml, in other embodiments 30 to 420mg/ml, in yet other embodiments 150 to 170mg/ml, in some embodiments 90mg/ml, 300mg/ml, 125mg/ml, 450mg/ml, or 500mg/ml;

in some embodiments, the solvent of both the synthetic molecule 1 solution and the synthetic molecule 2 solution may be secondary water, ultrapure water, physiological saline, or phosphate buffered solution at pH 7.4.

In some embodiments, the mass ratio of gel to hemostatic powder may be 1-10, in some embodiments 1:2, and in other embodiments 1:5.

The invention screens thousands of molecules which can be derived from polyoxyethylene polyoxypropylene segmented copolymer, polyacrylic acid and polyethylene glycol derivative, and finally discovers that the synthesized molecule 1 and the synthesized molecule 2 can form controllable crosslinked and degradable synthetic material gel, the gel can be degraded in simulated body fluid environment, the degradation period is 1 hour to 1 month, and the composite hemostatic system of the gel and hemostatic powder has potential application in the following fields: (1) a medical sponge; (2) epidermal hemostasis; (3) hemostasis of viscera; (4) arterial hemostasis.

Compared with the prior art, the invention has the following beneficial effects:

(1) Compared with the commercial hemostatic powder, the hemostatic powder of the compound hemostatic system has strong hemostatic capability, and when bleeding in a large area, the hemostatic powder is coated firstly to absorb water, and then the gel is coated, so that the defect that the hemostatic powder is easy to wash away can be overcome, and the defect that the water absorption capacity of the gel is insufficient when bleeding in a large area is overcome;

(2) In the composite hemostatic system, the gel can isolate wounds and surrounding tissues and can prevent the occurrence of tissue adhesion;

(3) In the composite system, the gel has higher mechanical strength and can meet the requirement of compression hemostasis;

(4) The degradation time of the composite hemostatic system can be regulated and controlled, so that the hemostatic requirements of wounds at different positions and with different degrees are met;

(5) The composite hemostatic system has good biocompatibility.

Detailed Description

The experimental methods used in the following examples are conventional methods unless otherwise specified.

Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.

Preparation of materials:

1. preparation method of four-arm oxyethylene polyoxypropylene polyoxyethylene succinimidyl ester

Four-arm oxyethylene polyoxypropylene polyoxyethylene (0.60 mmol) was dissolved in 30mL anhydrous dioxane. N, N' -disuccinimidyl ester (12.0 mmol) was dissolved in 20mL dry acetone and added slowly with magnetic stirring. 12.0mmol of 4- (dimethylamino) pyridine was dissolved in 20mL of anhydrous acetone and added slowly with magnetic stirring. And (3) activating for 6 hours at room temperature to obtain a four-arm oxyethylene polyoxypropylene polyoxyethylene precipitate. [1]

2. Preparation method of four-arm polyoxyethylene polyoxypropylene polyoxyethylene succinimidyl ester

Preparation method of Hexaarm polyoxyethylene polyoxypropylene polyoxyethylene succinimidyl ester Hexaarm oxyethylene polyoxypropylene polyoxyethylene (0.60 mmol) was dissolved in 30mL anhydrous dioxane. N, N' -disuccinimidyl ester (18.0 mmol) was dissolved in 30mL dry acetone and added slowly with magnetic stirring. 18.0mmol of 4- (dimethylamino) pyridine was dissolved in 30mL of anhydrous acetone and added slowly with magnetic stirring. And (3) activating for 6 hours at room temperature to obtain a hexa-arm oxyethylene polyoxypropylene polyoxyethylene precipitate. [1]

Preparation method of two-arm polyacrylic acid succinimide ester

Polyacrylic acid was poured into a mixed aqueous solution of 1-ethyl-3- (-3-dimethylaminopropyl) carbodiimide (0.5% w/w) and N-hydroxysuccinimide (0.25% w/w), and the mixture was stirred and mixed at room temperature to obtain two-arm polysuccinimide polyacrylate. [2]

[1].Huang，K.，et al.，Synthesis and Characterization of Self-Assembling Block Copolymers Containing Bioadhesive End Groups.Biomacromolecules，2002.3(2)：p.397-406.

[2].Deng，J.，et al.，Electrical bioadhesive interface for bioelectronics.Nature Materials，2021.20(2)：p.229-236.

Example 1,

130mg of a tetrabasic oxyethylene polyoxypropylene polyoxyethylene succinimidyl ester (a compound represented by the formula I, wherein m is 56, n is 23, p is 11, x is 4, R) ₁ Amino group) was dissolved in 1ml of physiological saline to give solution 1 (mass-volume concentration 130 mg/ml), and 130mg of a four-arm polyethylene glycol amino group (represented by formula VI, wherein m is 56, x is 4, R ₂ Amino group) was dissolved in 1ml of physiological saline to obtain a solution 2 (mass-volume concentrations of 130mg/ml, respectively); one mixed solution is respectively sucked by a double-tube syringe, then the mixed solution is injected into a cylindrical glass die, the cylindrical glass die is taken out after 30min, and the compressive strength is measured by a universal tensile machine, so that the strength can reach 3.2MPa, and the strength is high.

Degradation test: cylindrical gel with the diameter of 1cm and the height of 1cm is prepared according to the method, the gel is placed into a closed container filled with PBS buffer solution, then placed into a constant temperature shaking table with the temperature of 37+/-1 ℃, and the change condition of a gel sample in the buffer solution is observed at the speed of 100r/min until the gel sample is invisible to the naked eyes, and the gel in-vitro degradation time is recorded.

The degradation time of the hydrogel prepared in this example was measured as described above and was 5 days.

Subjected to blood pressure measurement: making a round hole with the diameter of 2mm on a pig abdominal aorta blood vessel with the diameter of 20mm, grafting the blood vessel to one end of a tee joint with a syringe and a pressure gauge, and uniformly coating commercial Fu and Tai degradable hemostatic powder on the round hole according to a preparation method of a composite system until the round hole is completely covered and the thickness is about 1mm; the range was then widened in a clockwise direction starting from the middle of the coated hemostatic powder, and the gel was coated with a double syringe system to completely cover the hemostatic powder, with a thickness of about 1mm after the gel. The inside of the blood vessel was filled with water by a syringe, and the pressure gauge number was observed to start rising, and at the point in time when the pressure gauge number started falling, the maximum blood pressure was considered to be sustained.

The pure Fu and Tai hemostatic powder can only bear the blood pressure of 12mmHg, and the compound hemostatic system can bear the blood pressure of 340 mmHg.

EXAMPLE 2,

200mg of a four-arm polyacrylamide (shown in formula II, wherein m is 112, R ₁ Amino group) was dissolved in 1ml of PBS to give solution 1 (mass-volume concentration: 200 mg/ml), 200mg of a four-arm polyoxyethylene polyoxypropylene polyoxyethylene succinimidyl ester (represented by formula IV, wherein m is 11, n is 112, p is 2, x is 4) was weighed and dissolved in 1ml of PBS to give solution 2 (mass-volume concentration: 200 mg/ml); one mixed solution is sucked by each double-tube syringe, then the mixed solution is injected into a transparent sample bottle at the same time, the sample bottle is inverted, and the non-flowing time of the liquid is gel time. The gel time of the system is 5s, the gel forming speed is high, and the gel can be formed on the surface of an object rapidly.

The hydrogel prepared in this example was tested for degradation properties by the method of example 1, and the degradation time was measured to be 3 days.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with a quick-acting powder of mesitylene, which was able to withstand 400mmHg, whereas the quick-acting powder of mesitylene was able to withstand only 15 mmHg.

EXAMPLE 3,

Weighing 100mg six-arm polyethylene glycol amino group (shown in formula III, wherein m is 28, x is 6, R ₁ Amino) was dissolved in 1ml PBS to give solution 1 (mass-volume concentration 100 mg/ml), 200mg of two-arm polyethylene glycol succinimidyl ester (shown in formula VI, wherein m is 56, x is 2, R ₂ Is succinimidyl ester) in 1ml PBS to obtain solution 2 (mass-volume concentration 200 mg/ml); using one of the syringes separatelySucking a mixed solution, coating the mixed solution on the surface of broken pigskin, and measuring the pulling force required by the re-separation of the pigskin by using a universal pulling machine to obtain the adhesive strength of the gel. The adhesive strength is 36kPa, which indicates that the gel can be well attached to the surface of pigskin and has high strength.

The hydrogel prepared in this example was tested for degradation performance according to the method in example 1, and the degradation time was measured to be 2 days, with a fast degradation rate.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available thrombin rapid-acting hemostatic powder into a composite system capable of withstanding 500mmHg of blood pressure, whereas commercially available thrombin hemostatic powder was capable of withstanding only 15mmHg of blood pressure.

EXAMPLE 4,

200mg of six-arm polyoxyethylene polyoxypropylene polyoxyethylene succinimidyl ester (shown in formula I, wherein m is 28, n is 12, p is 3, x is 6, R) ₁ Is amino) is dissolved in 1ml of ultrapure water to obtain solution 1 (mass-volume concentration is 200 mg/ml), 100mg of six-arm polyethylene glycol succinimidyl group (shown as formula Vl, wherein m is 28, x is 6, R ₂ Is succinimidyl ester) in 1ml of ultrapure water to obtain a solution 2 (mass-volume concentration 100 mg/ml); a mixed solution was aspirated with one of the double syringes, respectively, and simultaneously injected to obtain a gel.

The compression strength is 2.5Mpa and the adhesion strength is 46kPa (the same method as in example 3) measured by a universal tensile machine, and the strength is high.

The hydrogel prepared in this example was tested for degradation properties according to the method in example 1, and the degradation time was measured to be 5 days with a high degradation rate.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available blue crown hemostatic powder into a composite system capable of withstanding 350mmHg of blood pressure, whereas commercially available blue crown hemostatic powder can withstand only 9mmHg of blood pressure.

EXAMPLE 5,

150mg of six-arm polyethylene glycol amino group (shown in formula III, wherein m is 56, x is 6, R ₁ Is amino) is dissolved in 1ml of secondary water to obtain solution 1 (mass-volume concentration is 150 mg/ml), 150mg of six-arm polyethylene glycol succinimidyl ester (shown in formula VI, wherein m is 56, x is 6, R ₂ Is succinimidyl ester) in 1ml of secondary water to obtain solution 2 (mass-volume concentration is 150 mg/ml); a mixed solution was aspirated with one of the double syringes, respectively, and simultaneously injected to obtain a gel.

The compression strength is 5.4Mpa and the adhesion strength is 34kPa (the same method as in example 3) measured by a universal tensile machine, and the strength is high.

Each hydrogel prepared in this example was tested for degradation performance according to the method in example 1, and the degradation time was 15 days with a high degradation rate.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available alishitai hemostatic powder into a composite system capable of withstanding 450mmHg of blood pressure, whereas commercially available alishitai hemostatic powder was capable of withstanding only 13mmHg of blood pressure.

EXAMPLE 6,

150mg of eight-arm polyalkenyl (shown in formula II, wherein m is 28 and x is 8,R) ₁ Is amino) is dissolved in 1ml of secondary water to obtain solution 1 (mass-volume concentration is 150 mg/ml), 150mg of eight-arm polyethylene glycol mercapto group (shown in formula VI, wherein m is 56, x is 4, R ₂ To mercapto group) in 1ml of secondary water to give solution 2 (mass-volume concentration 150 mg/ml); a mixed solution was aspirated with one of the double syringes, respectively, and simultaneously injected to obtain a gel.

The compressive strength was measured at 2.4MPa and the adhesive strength was 22kPa (the same as in example 3) using a universal tensile machine.

The hydrogel prepared in this example was tested for degradation properties according to the method in example 1, and the degradation time was 7 days with a fast degradation rate.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available moxa micro-stop microfibril hemostatic collagen, which was able to withstand 220mmHg, whereas commercially available moxa micro-stop microfibril hemostatic collagen was able to withstand only 19 mmHg.

EXAMPLE 7,

Weighing 100mg of eight-arm polyethylene glycol aldehyde group (shown in formula III, wherein m is 32, and x is 8,R) ₁ Is aldehyde group) is dissolved in 1ml PBS solution to obtain solution 1 (mass-volume concentration is 100 mg/ml), 100mg of two-arm polyacrylic amino group (shown as formula V, wherein m is 22, x is 2, R ₂ Amino) was dissolved in 1ml PBS to give solution 2 (mass-volume concentration 100 mg/ml); a mixed solution was aspirated with one of the double syringes, respectively, and simultaneously injected to obtain a gel.

The compression strength is 3.4Mpa and the adhesion strength is 42kPa (the same method as in example 3) measured by a universal tensile machine, and the strength is high.

The hydrogel prepared in this example was tested for degradation performance according to the method in example 1, and the degradation time was measured to be 9 days, with a high degradation rate.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with a commercially available complex system capable of withstanding 540mmHg, whereas the commercially available QuikClot styptic powder was capable of withstanding only 15 mmHg.

EXAMPLE 8,

Weighing 100mg of four-arm polyacrylic acid sulfhydryl group (shown as formula II, wherein m is 16, R ₁ Is mercapto) in 1ml PBS to obtain solution 1 (mass-volume concentration is 100 mg/ml), and weighing 100mg of four-arm polyoxyethylene polyoxypropylene polyoxyethylene alkenyl (shown in formula IV, wherein m is 12, n is 50, p is 4, x is 4, R ₁ Alkenyl) was dissolved in 1ml of PBS to give solution 2 (mass-volume concentration 100 mg/ml); one mixed solution is sucked by each double-tube syringe, then the mixed solution is injected into a transparent sample bottle at the same time, the sample bottle is inverted, and the non-flowing time of the liquid is gel time. The gel time of the system is 20s, the gel forming speed is high, and the gel can be formed on the surface of an object rapidly.

The hydrogel prepared in this example was tested for degradation properties by the method of example 1, and the degradation time was measured to be 6 days.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available alishi hemostatic powder into a composite system capable of withstanding 240mmHg of blood pressure, whereas alishi hemostatic powder was capable of withstanding only 13mmHg of blood pressure.

EXAMPLE 9,

200mg of a four-arm polyacrylamide (shown in formula II, wherein m is 42, R ₁ Amino) was dissolved in 1ml PBS to give solution 1 (mass-volume concentration: 200 mg/ml), 200mg of a four-arm polyoxyethylene polyoxypropylene polyoxyethylene aldehyde group (represented by formula IV, wherein m is 50, n is 12, p is 6, x is 4, R) ₁ Alkenyl) was dissolved in 1ml of PBS to give solution 2 (mass-volume concentration 200 mg/ml); one mixed solution is sucked by each double-tube syringe, then the mixed solution is injected into a transparent sample bottle at the same time, the sample bottle is inverted, and the non-flowing time of the liquid is gel time. The gel time of the system is 12s, the gel forming speed is high, and the gel can be formed on the surface of an object rapidly.

The hydrogel prepared in this example was tested for degradation properties by the method of example 1, and the degradation time was measured to be 5 days.

The ability of the gel to withstand blood pressure was measured as in example 1 by combining the present gel with commercially available blue crown hemostatic powder into a composite system capable of withstanding 420mmHg of blood pressure, whereas commercially available blue crown hemostatic powder can withstand only 9mmHg of blood pressure.

The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A controllable crosslinking and degradation synthetic material is formed by mixing two kinds of polyoxyethylene polyoxypropylene segmented copolymer and polyacrylic acid, namely a synthetic molecule 1 and a synthetic molecule 2, wherein the synthetic molecule 1 is any one of a formula I and a formula II:

，

in the formula I and the formula II, m, n and p are 28 to 112, x represents the number of arms and is 1 to 8,

the synthetic molecule 2 is of formula IV or formula V:

，

in the formula IV and the formula V, m, n and p are 2-112, x represents the number of arms of 1-8,

r in the formula I, the formula II or the formula IV ₁ Or R is ₂ Is amino, aldehyde, succinimidyl ester, alkenyl or mercapto.

2. The controllably crosslinked, degradable synthetic material of claim 1, said synthetic molecule 1 being any one of the following compounds:

2) The compound is shown as a formula II, wherein m is 28-112, x is 4-8, R ₁ Is amino.

3. The controllably crosslinked, degradable synthetic material of claim 1, said synthetic molecule 2 being any one of the following compounds:

2) Wherein m is 22, x is 2, R ₂ Is amino.

4. A controllably crosslinkable and degradable synthetic material according to any one of claims 1-3, characterized in that it consists of a compound of formula II wherein m is 28-112, x is 4-8, r, and a compound of formula IV ₁ Is amino, m is 11-50, n is 12-112, p is 2-6, x is 4, R in the compound shown in the formula IV ₂ Is amino or mercapto.

5. The controllably crosslinked, degradable synthetic material of claim 1, wherein the mass ratio of synthetic molecule 1 to synthetic molecule 2 is 1:0.5-2.

6. The controllably crosslinked, degraded synthetic material according to any one of claims 1-3 or 5, wherein the controllably crosslinked, degraded synthetic material forms a gel and the hemostatic powder forms a composite hemostatic system, the mass ratio of the gel to the hemostatic powder being 1:10.

7. The controllably crosslinked, degradable synthetic material of claim 6, wherein the hemostatic powder is regenerated cellulose-based hemostatic powder, zeolite-based hemostatic powder, or protein-based hemostatic powder.

8. The controllably crosslinked, degradable synthetic material of claim 6, a method of making the composite hemostatic system comprising: preparing a controllable crosslinked and degradable synthetic material into a solution with a certain proportion, and then coating the solution on the hemostatic powder to prepare the composite hemostatic system based on the controllable crosslinked and degradable synthetic material gel and the hemostatic powder, wherein the controllable crosslinked and degradable synthetic material consists of a synthetic molecule 1 and a synthetic molecule 2.

9. The controllably crosslinked and degraded synthetic material of claim 8, wherein the concentration of synthetic molecules 1 in the solution is 10-500 mg/ml; the concentration of the synthetic molecules 2 in the solution is 30-800 mg/ml; the solvent of the solution is secondary water, ultrapure water, normal saline or phosphate buffer solution with the pH of 7.4.