CN118750658A - A high-viscosity anti-adhesion hydrogel and its preparation method and application - Google Patents

Abstract

The present invention relates to the field of biomedical materials technology, in particular to the field of A61L24/08, and more specifically to a high-viscosity anti-adhesion hydrogel and its preparation method and application. The raw materials for preparing the high-viscosity anti-adhesion hydrogel include sodium carboxymethyl cellulose, polyethylene glycol, clay, sodium alginate and liquid phase. The obtained hydrogel has good adhesion and stability, slow degradation cycle, and is a non-toxic, non-irritating, and biocompatible hydrogel.

Description

A high-viscosity anti-adhesion hydrogel and its preparation method and application

Technical Field

The present invention relates to the field of biomedical material technology, in particular to the field of A61L24/08, and more specifically to a high-viscosity anti-adhesion hydrogel and a preparation method and application thereof.

Background Art

Adhesions are unwanted tissue growths that occur between adjacent layers of body tissue or between tissues and internal organs. Adhesions often form during the healing process after surgery and, when present, prevent the normal movement of these tissues and organs relative to adjacent structures. The medical and scientific communities have investigated methods of reducing the formation of postoperative adhesions through the use of high molecular weight, carboxyl-containing biopolymers. These biopolymers can form hydrogels that act as a physical barrier separating tissues during the healing process, thereby preventing adhesions from forming between normal adjacent structures. After the tissues have healed and are no longer needed, the hydrogel should be cleared from the body to allow the affected tissue to function more normally.

In the field of clinical medicine, adhesion refers to an abnormal structure formed by the connection of connective tissue fibers with adjacent tissues or organs. Its size can range from a thin film of fiber to a dense vascular scar. The formation of adhesions is universal. It is reported that more than 50% of abdominal and pelvic surgeries will lead to adhesions of varying degrees. Adhesions often lead to serious clinical complications, including intestinal obstruction, infertility, chronic pelvic inflammatory disease and postoperative epilepsy, which increase the difficulty of reoperation and the potential for complications. In surgical operations, how to prevent postoperative adhesions is one of the important research topics at home and abroad.

Hydrogel is a polymer material that swells in water but is insoluble in water. It has a complex tertiary network structure formed by its intermolecular interaction and has excellent physical and chemical properties and biological characteristics. The hydrogel has a smooth surface, good biocompatibility, moderate water absorption capacity, and can undergo repeated hydration when in contact with tissues. Injectable hydrogel refers to a hydrogel with a certain fluidity that can gel in situ after being injected into the human body, thus eliminating the need for invasive surgery. This effectively avoids the risk of infection and reduces the patient's pain.

At present, the modified polysaccharide molecules can react quickly to form hydrogels, which has certain advantages in the field of biodegradable hydrogels and has the potential for commercial applications. However, the hydrogels have problems such as too fast degradation rate, low viscosity and high cost.

Patent CN105327388A discloses a hydrogel prepared by mixing aldehyded sodium alginate and amino carboxymethyl sodium alginate, which has high pig skin adhesion strength, but the adhesion strength is reduced in a moist skin tissue environment and cannot meet actual medical needs; CN106075553A discloses a medical bioadhesive, which uses dopamine to improve the adhesion strength of the adhesive in a moist skin tissue environment, but the cost is relatively high.

US Patent No. 4,141,973 discloses a hydrogel using hyaluronic acid (HA) to prevent adhesion. However, since HA is relatively soluble and easily degraded in the body, it has a relatively short half-life of 1-3 days in the body, which limits its role as an adhesion preventive. The disadvantage of this patent is that they have a short biological residence time and therefore may not stay at the repair site long enough to produce the desired anti-adhesion effect.

Summary of the invention

In view of the deficiencies in the prior art, the present invention provides a high-viscosity anti-adhesion hydrogel, which is viscous and injectable at room temperature and can quickly become a non-flowing hydrogel when injected into the body. It has the characteristics of reducing the incidence of adhesion formation during and after surgery, preventing reorganization after secondary surgery, and anti-adhesion. In addition, the hydrogel is low in cost and has a long degradation cycle, and is a bioabsorbable hydrogel.

The hydrogel prepared by the invention is a transparent semisolid with uniform texture, strong adhesion on the skin and mucous membrane and good effect.

In order to achieve the above technical objectives, the technical solutions provided by the present invention are as follows:

The first aspect of the present invention provides a high-viscosity anti-adhesion hydrogel, the preparation raw materials of which include: sodium carboxymethyl cellulose (CMC-Na), polyethylene glycol (PEO), clay, sodium alginate and a liquid phase.

Preferably, the average molecular weight of PEO is 1 million to 5 million; more preferably, the average molecular weight of PEO is 4 million.

Preferably, the viscosity of the sodium carboxymethyl cellulose is 1000-10000 mPa.s at 25°C; more preferably, the viscosity is 5000-10000 mPa.s.

Preferably, the liquid phase comprises: one of deionized water, water for injection, and PBS buffer solution; more preferably, the liquid phase is PBS buffer solution.

Preferably, the sodium carboxymethyl cellulose, polyethylene glycol, clay and sodium alginate are all in the form of aqueous solutions; the volume ratio of the sodium carboxymethyl cellulose solution, the polyethylene glycol solution, the clay solution and the sodium alginate solution is (1-2): (1-2): (0.5-1): (0.5-1).

Preferably, the mass concentration of the sodium carboxymethylcellulose solution is 0.5-2%; more preferably, the mass concentration is 1%.

Preferably, the pH of the sodium carboxymethyl cellulose solution is 4-8.

Preferably, the mass concentration of the polyethylene glycol solution is 0.5-3%; more preferably, the mass concentration is 1-2%.

Preferably, the mass concentration of the clay solution is 2-10%; more preferably, the mass concentration is 5%.

The added clay can be located between the carboxyl group of CMC-Na and the ether oxygen atom of the polyether, and can attract valence electrons with the carboxyl group and oxygen atom to form ionic bonds. The trivalent ions can provide tighter ionic bonding between polymers in the solution and improve the viscosity and stability of the hydrogel.

Preferably, the mass concentration of the sodium alginate solution is 0.5-3%; more preferably, the mass concentration is 0.5-1%.

Sodium alginate can improve the bioadhesion of hydrogels, and further form a stable high-viscosity hydrogel system through the hydrogen bonding effect of a small amount of sodium alginate and sodium carboxymethyl cellulose.

The present invention prepares a gel material by accurately mixing CMC-Na, PEO, clay and sodium alginate, and the gel material forms a spatial network structure and slowly degrades under body temperature conditions. As time goes by, the rigidity of the gel decreases and the original spatial network structure is gradually lost. The gel is a bioabsorbable hydrogel.

The second aspect of the present invention provides a method for preparing a high-viscosity anti-adhesion hydrogel, comprising at least the following steps:

S1. Sodium carboxymethyl cellulose, polyethylene glycol, clay and sodium alginate are prepared into solutions respectively;

S2, acidifying the sodium carboxymethyl cellulose solution to adjust the pH to 4.0-8.0, and uniformly mixing the sodium carboxymethyl cellulose solution, the polyethylene glycol solution, the clay solution and the sodium alginate solution to form a high-viscosity hydrogel system;

S3. Take the above high-viscosity hydrogel into a centrifuge tube, add the liquid phase to form a high-viscosity anti-adhesion hydrogel; and observe the degradation at 37°C.

Further preferably, the method for preparing the high-viscosity anti-adhesion hydrogel comprises at least the following steps:

S1. Sodium carboxymethyl cellulose with a viscosity of 1500-3100 mPa.s at 25°C, polyethylene glycol with an average molecular weight of 4 million, clay and sodium alginate with a viscosity of 200 mPa.s at 25°C are respectively prepared into a sodium carboxymethyl cellulose solution with a mass concentration of 1%, a polyethylene glycol solution with a mass concentration of 1%, a clay solution with a mass concentration of 2%, and a sodium alginate solution with a mass concentration of 0.5%;

S2, acidifying the sodium carboxymethyl cellulose solution by adding HCl to adjust the pH to 4.0, and uniformly mixing the sodium carboxymethyl cellulose solution, the polyethylene glycol solution, the clay solution and the sodium alginate solution in a volume ratio of 1:1:0.5:0.5 to form a high-viscosity hydrogel system;

S3. Take the above high-viscosity hydrogel into a centrifuge tube, add PBS solution with a pH of 7.4 to form a high-viscosity anti-adhesion hydrogel; and observe the degradation at 37°C.

The third aspect of the present invention provides the application of high-viscosity anti-adhesion hydrogel, which is applied to the preparation of products for preventing and treating intrauterine adhesions, products for recovering uterine adhesions, and products for tissue repair.

Beneficial Effects

(I) The present invention affects the degree of ionic bonding between the carboxyl group of CMC-Na and the ether oxygen atom by adjusting the pH of the CMC-Na solution; the pH value increases the number of protonated carboxyl residues in CMC-Na, thereby increasing the number of hydrogen bonds that may be formed with the polyether, and the carboxyl groups on the polysaccharide are negatively charged and repel each other with PEO to form a weak hydrogen bond gel with structural integrity; the anti-adhesion film properties of the hydrogel are controlled by adjusting the pH, the number of carboxyl groups and the polyether in the CMC-Na and PEO binding complex.

(ii) The present invention adopts a combination of sodium carboxymethyl cellulose, polyethylene glycol, clay and sodium alginate to prepare a high-viscosity anti-adhesion hydrogel. By screening the formula, the prepared hydrogel has high viscosity and stability, and prolongs the anti-adhesion effect time of the hydrogel.

(III) The high-viscosity anti-adhesion hydrogel prepared by the present invention is injectable, has little trauma, is easy to operate, and can be in close contact with tissues. The hydrogel is non-toxic, non-irritating, and has good biocompatibility.

(IV) The formula of the high viscosity anti-adhesion hydrogel prepared by the present invention is precisely set, with the mass concentration of sodium carboxymethyl cellulose being 1%, the mass concentration of polyethylene glycol being 1%, the mass concentration of clay being 5%, and the mass concentration of sodium alginate being 0.5%-1%. By controlling the amount of each formula, the prepared hydrogel has better adhesion and stability, and a slow degradation cycle, and is a bioabsorbable hydrogel.

(V) The high-viscosity anti-adhesion hydrogel prepared by the present invention can be used to prevent and treat intrauterine adhesions, achieve uterine adhesion recovery and tissue repair, and has a good medical use effect.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a mixed solution system of step S2 of a comparative example.

Figure 2 shows the gelation of the comparative mixed solution after adding PBS.

FIG3 is a schematic diagram of the mixed solution system in step S2 of Experiment 5 in Example 2.

FIG. 4 shows the hydrogel formation after adding PBS to the mixed solution of Experiment 5 in Example 2.

FIG5 is a schematic diagram of the mixed solution system in step S2 of Experiment 33 in Example 8.

FIG6 shows the hydrogel formation of the mixed solution of Experiment 33 in Example 8 after adding PBS.

DETAILED DESCRIPTION

Comparative Example

This example provides a method for preparing a hydrogel, which comprises the following steps:

S1. Select CMC-Na with a viscosity of 1500-3100 mPa.s at 25°C and PEO with an average molecular weight of 4 million, prepare 1% CMC-Na solution and 1% PEO solution respectively, and the solvent is water;

S2. Acidify the CMC-Na solution to pH 4.0 by adding an appropriate amount of HCl, take 1 mL of the CMC-Na solution with a pH of 4.0 and 1 mL of the PEO solution and mix them evenly, and the formed hydrogel has a low viscosity;

S3. 10 mL PBS (pH=7.4) was added to the above hydrogel system, but no soft hydrogel was formed.

FIG. 1 is a mixed solution system of step S2 of a comparative example.

Figure 2 shows the gelation of the comparative mixed solution after adding PBS.

Example 1

In the first aspect of this example, a hydrogel is provided, the raw materials of which are: CMC-Na with a viscosity of 1500-3100 mPa.s, PEO with an average molecular weight of 4 million, and a third component.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1, select CMC-Na with a viscosity of 1500-3100 mPa.s at 25°C, PEO with an average molecular weight of 4 million and the third component, respectively prepare a CMC-Na solution with a mass concentration of 1%, a PEO solution with a mass concentration of 1% and a third component solution, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, taking 1 mL of the CMC-Na solution with a pH of 4.0, 1 mL of a 1% PEO solution and a certain volume of the third component solution and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 1.

Table 1

Example 2

On the basis of Example 1, the effect of the fourth component on the solution viscosity and gelling property was investigated.

In the first aspect of this example, a hydrogel is provided, the raw materials of which are: CMC-Na with a viscosity of 1500-3100 mPa.s, PEO with an average molecular weight of 4 million, clay and a fourth component.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1, select CMC-Na with a viscosity of 1500-3100mPa.s at 25°C, PEO with an average molecular weight of 4 million, clay and the fourth component, respectively prepare a CMC-Na solution with a mass concentration of 1%, a PEO solution with a mass concentration of 1%, a clay solution with a mass concentration of 5%, and a fourth component solution, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, taking 1 mL of the CMC-Na solution with a pH of 4.0, 1 mL of the PEO solution, 0.5 mL of the clay solution and a certain volume of the fourth component solution and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

FIG3 is a schematic diagram of the mixed solution system in step S2 of Experiment 5 in Example 2.

FIG. 4 shows the hydrogel formation after adding PBS to the mixed solution of Experiment 5 in Example 2.

The specific process parameters are shown in Table 2.

Table 2

When the mass concentration and volume of CMC-Na solution, PEO solution and clay solution remain unchanged, different hydrogels are prepared by adding different fourth components; when CMC-Na, PEO, clay and sodium alginate are mixed, the viscosity of the obtained solution is relatively large, and a uniform colloidal structure can be formed by adding a certain amount of PBS to the mixed solution.

When CMC-Na, PEO, clay and sodium alginate are combined, the anion-containing CMC-Na and sodium alginate react with the cation-containing clay and PEO to obtain a system with higher viscosity. At the same time, ionic bonds are also formed between CMC-Na and sodium alginate, thereby further increasing the viscosity and stability of the system.

Example 3

Based on Example 2, the effect of the order of adding raw materials on the hydrogel was investigated.

In the first aspect of this example, a hydrogel is provided, the raw materials of which are: CMC-Na with a viscosity of 1500-3100 mPa.s, PEO with an average molecular weight of 4 million, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1. Select CMC-Na with a viscosity of 1500-3100 mPa.s at 25°C, PEO with an average molecular weight of 4 million, clay and sodium alginate, and prepare a CMC-Na solution with a mass concentration of 1%, a PEO solution with a mass concentration of 1%, a clay solution with a mass concentration of 5%, and a sodium alginate solution with a mass concentration of 1%, respectively, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, taking 1 mL of the CMC-Na solution with a pH of 4.0, 1 mL of the PEO solution, 0.5 mL of the clay solution and 1 mL of the sodium alginate solution, respectively, and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 3.

Table 3

By examining the different addition orders of the four solutions, it was found that when CMC-Na, PEO, clay, and sodium alginate solutions were mixed in this order, the viscosity of the mixed solution was relatively large. After adding a certain amount of PBS to the mixed solution, the formed hydrogel was relatively uniform and did not disperse.

When the four solutions are added in different orders, the interactions between ions may be different. When CMC-Na, PEO, clay, and sodium alginate solutions are added in sequence, the resulting solution system is relatively stable.

Example 4

On the basis of Example 3, the effect of the mass concentration of clay on the hydrogel was investigated.

In the first aspect of this example, a hydrogel is provided, the raw materials of which are: CMC-Na with a viscosity of 1500-3100 mPa.s at 25°C, PEO with an average molecular weight of 4 million, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1. Select CMC-Na with a viscosity of 1500-3100 mPa.s, PEO with an average molecular weight of 4 million, clay and sodium alginate, and prepare a 1% CMC-Na solution, a 1% PEO solution, clay solutions with different mass concentrations, and a 1% sodium alginate solution, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, taking 1 mL of the CMC-Na solution with a pH of 4.0, 1 mL of the PEO solution, 0.5 mL of the clay solution and 1 mL of the sodium alginate solution, respectively, and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 4.

Table 4

The effect of different clay concentrations on hydrogel was investigated. The experiment found that when the mass concentration of clay was small, the solution formed by mixing the four solutions had relatively large fluidity and average viscosity, and the hydrogel formed by adding a certain amount of PBS to the mixed solution was relatively uniform; when the mass concentration of clay was 5%, the solution formed by mixing the four solutions had slow fluidity and large viscosity, and the hydrogel formed by adding a certain amount of PBS was relatively uniform; when the mass concentration of clay was 10%, the solution formed by mixing the four solutions was basically non-flowing and had the highest viscosity, and fragmented hydrogel was formed by adding a certain amount of PBS.

In addition, the prepared clay solution with a mass concentration of 10% has poor stability and the solution will solidify in a short time, which is inconvenient to use.

Example 5

Based on Example 4, the effect of the average molecular weight of PEO on the hydrogel was investigated.

In a first aspect, this example provides a hydrogel, the raw materials of which are: CMC-Na with a viscosity of 1500-3100 mPa.s, PEO with different average molecular weights, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1. Select CMC-Na with a viscosity of 1500-3100 mPa.s at 25°C, PEO with different average molecular weights, clay and sodium alginate, and prepare 1% CMC-Na solution, 1% PEO solution, 5% clay solution and 1% sodium alginate solution, respectively, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, taking 1 mL of the CMC-Na solution with a pH of 4.0, 1 mL of the PEO solution, 0.5 mL of the clay solution and 1 mL of the sodium alginate solution, respectively, and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 5.

Table 5

By examining PEO with different average molecular weights, it was found that there is a certain relationship between the viscosity of the overall mixed solution and the average molecular weight of PEO. The larger the average molecular weight of PEO, the greater the viscosity of the overall mixed solution. However, when the average molecular weight of PEO is too large, the fluidity of the solution after mixing the four solutions is poor. When the average molecular weight of PEO is 4 million, the viscosity of the mixed solution is better and the gelation is more uniform.

Example 6

Based on Example 5, the effects of the viscosity of CMC-Na and the pH value of the solution on the hydrogel were investigated.

In the first aspect of this example, a hydrogel is provided, the raw materials of which are: CMC-Na with different viscosities, PEO with an average molecular weight of 4 million, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1. Select CMC-Na with different viscosities, PEO with an average molecular weight of 4 million, clay and sodium alginate, and prepare CMC-Na solution with a mass concentration of 1%, PEO solution with a mass concentration of 1%, clay solution with a mass concentration of 5%, and sodium alginate solution with a mass concentration of 0.5%, respectively, and the solvent is water;

S2, acidifying the CMC-Na solution by adding an appropriate amount of HCl, taking 1 mL of CMC-Na solution, 1 mL of PEO solution, 0.5 mL of clay solution and 0.5 mL of sodium alginate solution and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 6.

Table 6

By investigating CMC-Na with different viscosities, it was found that there is a certain relationship between the viscosity of CMC-Na and the viscosity of the overall solution. In addition, the pH of the CMC-Na solution also has a certain influence on the gelation. When the pH value tends to be weakly acidic, the formed hydrogel is more uniform. It may be that the pH value increases the number of protonated carboxyl residues in CMC-Na, thereby increasing the number of hydrogen bonds that may be formed with the polyether. The degree of ionic bonding between the carboxyl group of CMC-Na and the ether oxygen atom can be affected by adjusting the pH of the solution.

Example 7

Based on Example 6, the effect of the concentration of each component on the hydrogel was investigated.

In a first aspect, this example provides a hydrogel, the raw materials of which are: CMC-Na with a viscosity of 10000 mPa.s at 25°C, PEO with an average molecular weight of 4 million, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1, select CMC-Na with a viscosity of 10000mPa.s, PEO with an average molecular weight of 4 million, clay and sodium alginate, prepare CMC-Na solution, PEO solution, clay solution and sodium alginate solution of different concentrations respectively, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, and mixing 1 mL of the CMC-Na solution, 1 mL of the PEO solution, 1 mL of the clay solution, and 1 mL of the sodium alginate solution to form a hydrogel of a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

The specific process parameters are shown in Table 7.

Table 7

By examining the different concentrations of the four solutions, the experiment found that when the concentrations of the four solutions were 1% CMC-Na, 1% PEO, 5% clay and 0.5% sodium alginate, the viscosity of the overall solution was relatively large. After a certain volume of PBS was added to the mixed solution, the hydrogel formed was more uniform.

Example 8

Based on Example 7, the effect of volume ratio on the hydrogel was investigated.

In a first aspect, this example provides a hydrogel, the raw materials of which are: CMC-Na with a viscosity of 10000 mPa.s at 25°C, PEO with an average molecular weight of 4 million, clay and sodium alginate.

The second aspect of this example provides a method for preparing a hydrogel, which comprises the following steps:

S1, select CMC-Na with a viscosity of 10000mPa.s, PEO with an average molecular weight of 4 million, clay and sodium alginate, prepare CMC-Na solution with a mass concentration of 1%, PEO solution with a mass concentration of 1%, clay solution with a mass concentration of 5%, sodium alginate solution with a mass concentration of 0.5%, respectively, and the solvent is water;

S2, acidifying the CMC-Na solution to a pH of 4.0 by adding an appropriate amount of HCl, and taking different volumes of CMC-Na solution, PEO solution, clay solution and sodium alginate solution and mixing them evenly to form a hydrogel with a certain viscosity;

S3. Add 10 mL PBS (pH=7.4) to the above hydrogel system and observe the gelation.

FIG5 is a schematic diagram of the mixed solution system in step S2 of Experiment 33 in Example 8.

FIG6 shows the hydrogel formation of the mixed solution of Experiment 33 in Example 8 after adding PBS.

The third aspect of this example provides the application of high-viscosity anti-adhesion hydrogel. The hydrogel in experimental group 33 is used in the preparation of products for preventing and treating intrauterine adhesions, uterine adhesion recovery products, and tissue repair products.

The specific process parameters are shown in Table 8.

Table 8

By examining the different volumes of the four solutions, the experiment found that when the volume ratio of the four solutions was 1:1:1:1, the viscosity of the overall solution was greater and the formed hydrogel was more uniform.

The PEO with different average molecular weights was purchased from Adamas.

The CMC-Na with different viscosities was purchased from Adamas.

The clay was purchased from BYK.

The sodium alginate (viscosity of 200 mPa.s at 25° C.) was purchased from aladdin.

Performance Testing

Stability test

The hydrogel samples prepared in Experiment 5, Experiment 33 and the comparative example were placed in PBS at 37° C. and pH 7.4, and the degradation was observed and the in vitro degradation time was recorded. The test results are detailed in Table 9.

Table 9

Example Degradation time/d Comparative Example / Experiment 5 ＞30d Experiment 33 ＞30d

Claims (10)

1. A high-viscosity anti-adhesion hydrogel, characterized in that the preparation raw materials include: sodium carboxymethyl cellulose, polyethylene glycol, clay, sodium alginate and liquid phase. 2. The high-viscosity anti-adhesion hydrogel according to claim 1, characterized in that the average molecular weight of the polyethylene glycol is 1 million to 5 million. 3. The high-viscosity anti-adhesion hydrogel according to claim 2, characterized in that the viscosity of the sodium carboxymethyl cellulose at 25°C is 1000-10000 mPa.s. 4. The high-viscosity anti-adhesion hydrogel according to claim 3, characterized in that the liquid phase comprises: one of deionized water, water for injection, and PBS buffer solution. 5. The high-viscosity anti-adhesion hydrogel according to claim 4, characterized in that the sodium carboxymethyl cellulose, polyethylene glycol, clay and sodium alginate are all in the form of aqueous solutions; the volume ratio of the sodium carboxymethyl cellulose solution, the polyethylene glycol solution, the clay solution and the sodium alginate solution is (1-2): (1-2): (0.5-1): (0.5-1). 6. The high-viscosity anti-adhesion hydrogel according to claim 5, characterized in that the mass concentration of the sodium carboxymethylcellulose solution is 0.5-2%. 7. The high-viscosity anti-adhesion hydrogel according to claim 6, characterized in that the mass concentration of the polyethylene glycol solution is 0.5-3%. 8. The high-viscosity anti-adhesion hydrogel according to claim 7, characterized in that the mass concentration of the sodium alginate solution is 0.5-3%. 9. A method for preparing the high-viscosity anti-adhesion hydrogel according to claim 8, characterized in that it comprises at least the following steps: S1. Sodium carboxymethyl cellulose, polyethylene glycol, clay and sodium alginate are prepared into solutions respectively; S2, acidifying the sodium carboxymethyl cellulose solution to adjust the pH to 4.0-8.0, and uniformly mixing the sodium carboxymethyl cellulose solution, the polyethylene glycol solution, the clay solution and the sodium alginate solution to form a high-viscosity hydrogel system; S3. Take the above high-viscosity hydrogel into a centrifuge tube, add the liquid phase to form a high-viscosity anti-adhesion hydrogel; and observe the degradation at 37°C. 10. An application of the high-viscosity anti-adhesion hydrogel according to claim 8, characterized in that it is applied to the preparation of products for preventing and treating intrauterine adhesions, products for restoring uterine adhesions, and products for repairing tissues.