Preparation method of in-situ hydrazone bond injectable hydrogel and application in preventing abdominal cavity adhesion

Abstract

The application discloses a preparation method of an in-situ hydrazone bond injectable hydrogel and application thereof to preventing abdominal cavity adhesion, and belongs to the field of medical biomaterials. The application takes 8-arm-PEG10000-CHO with an aldehyde group at a terminal and 8-arm-PEG10000-HZ with a hydrazine group at a terminal as raw materials, forms a hydrazone bond through a Schiff base reaction, and obtains PCA supermolecular hydrogel through in-situ construction; the preparation method of the application does not need a chemical crosslinking agent, can quickly form a gel at room temperature, is simple and controllable in process, and the prepared hydrogel has excellent injectability, self-healing performance, biodegradability and biocompatibility, can form a stable physical barrier in-situ on an abdominal surgery wound, effectively inhibits inflammatory cell infiltration and collagen fiber deposition, has a significant prevention effect on light, medium and severe abdominal cavity adhesion, and especially still has excellent protection capability in a severe inflammatory adhesion model induced by talc, thereby providing a safe and effective new scheme for preventing and treating postoperative abdominal cavity adhesion.

Description

Technical Field

[0001] This invention belongs to the field of medical biomaterials, and particularly relates to a method for preparing an in-situ injectable hydrogel with hydrazone bonds and its application in the prevention of abdominal adhesions after abdominal surgery. Background Technology

[0002] Abdominal adhesions are a common and serious complication after abdominal surgery. Caused by surgical trauma, infection, inflammation, and other factors, they result in abnormal fibrous adhesions between abdominal tissues and organs, leading to a series of adverse consequences such as intestinal obstruction, chronic pelvic pain, and female infertility, severely impacting patients' postoperative quality of life. Epidemiological data shows that the incidence of abdominal adhesions after abdominal surgery is as high as 70% to 90%, generating billions of dollars in medical costs annually. It is also a core contributing factor to repeat surgery, imposing a heavy physical, psychological, and economic burden on patients.

[0003] Currently, clinical approaches to prevent and treat postoperative abdominal adhesions mainly fall into three categories: drug therapy, physical barrier intervention, and reoperation for adhesion release. However, all of these approaches have significant technical limitations. Drug therapy often uses anti-inflammatory drugs and corticosteroids, which are not specifically designed for abdominal adhesions. This makes it difficult to completely block the adhesion process, and long-term use can interfere with normal wound healing and increase the risk of postoperative infection. Reoperation for adhesion release not only carries the risk of anesthesia and surgical complications but also easily causes new tissue trauma, leading to a vicious cycle of "adhesion-release-re-adhesion." Physical barriers are currently the mainstream clinical strategy for preventing adhesions, with sodium hyaluronate products being the most widely used. However, these products suffer from problems such as a mismatch between degradation rate and tissue repair cycle, insufficient mechanical strength, and limited protective effect against adhesions induced by severe inflammation, making them insufficient to meet clinical needs.

[0004] Hydrogels have become a research hotspot in the field of postoperative adhesion prevention due to their high water content, mechanical properties similar to biological tissues, and excellent biocompatibility. Injectable hydrogels can fill irregular surgical wounds in situ through minimally invasive surgery, forming a physical isolation barrier. Simultaneously, the inflammatory microenvironment can be regulated through material structure design, inhibiting fibrin deposition and collagen proliferation, demonstrating significant advantages in anti-adhesion applications. However, existing anti-adhesion hydrogels still face several technical bottlenecks: complex preparation processes requiring the introduction of toxic chemical cross-linking agents, posing biosafety risks; uncontrollable material degradation rates, making it difficult to maintain a stable barrier effect during the critical tissue repair window; insufficient mechanical properties, making it difficult to balance self-healing and injectability, and easily subject to mechanical damage in vivo, resulting in loss of barrier function; and poor protective effects against severe injuries and inflammation-induced abdominal adhesions, limiting their clinical translation and application. Therefore, developing an injectable hydrogel with a simple preparation process, high biosafety, controllable performance, and excellent anti-adhesion effect is a pressing technical problem to be solved in the clinical prevention and treatment of abdominal adhesions. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing materials and technologies for preventing and treating abdominal adhesions, and to provide a method for preparing an in-situ injectable hydrogel with hydrazone bonds and its application in preventing abdominal adhesions.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] The preparation method of in-situ injectable hydrogels containing hydrazone bonds includes the following steps:

[0008] 1) Dissolve 8-arm-PEG10000-CHO in deionized water to obtain a PEG-CHO solution; prepare a PEG-HZ solution using the same method.

[0009] 2) Add the PEG-HZ solution to the PEG-CHO solution using a pipette at a volume ratio of 1:1, vortex to mix them completely, and allow to stand at room temperature to react, thus obtaining an in-situ injectable hydrazone hydrogel, namely PCA supramolecular hydrogel.

[0010] Furthermore, the concentrations of both the PEG-CHO solution and the PEG-HZ solution are 20-30 mg / mL.

[0011] Furthermore, the molecular weights of both 8-arm-PEG10000-CHO and 8-arm-PEG10000-HZ are 10000.

[0012] Furthermore, the hydrogel is a three-dimensional porous network supramolecular hydrogel constructed by cross-linking the aldehyde group of 8-arm-PEG10000-CHO and the hydrazide group of 8-arm-PEG10000-HZ through a Schiff base reaction to form hydrazone bonds. The entire reaction system does not require the introduction of additional chemical cross-linking agents and can quickly gel at room temperature.

[0013] Furthermore, the hydrogel has a three-dimensional porous network structure with uniform pore distribution, exhibiting excellent material permeation and water molecule exchange capabilities.

[0014] Furthermore, the hydrogel exhibits shear-thinning properties, with its viscosity decreasing significantly with increasing shear rate. Under alternating cycles of high and low strain, the storage modulus (G') and loss modulus (G'') of the hydrogel can rapidly recover to their initial values, maintaining stable recovery capabilities after four cycles. It can also rapidly reconstruct its network structure after mechanical damage in vivo, maintaining the integrity of its barrier function.

[0015] Furthermore, the hydrogel possesses excellent self-healing properties. After the cut surfaces of the hydrogel are tightly adhered, the interface color can still be integrated and the structure repaired without any obvious fracture surface. It can be continuously and uniformly extruded through a syringe, and can quickly return to the gel state after extrusion, exhibiting excellent injectability and clinical minimally invasive surgical compatibility.

[0016] Furthermore, the hydrogel exhibits concentration-dependent swelling and degradation properties, achieving a balanced swelling state in deionized water; it can be completely degraded under simulated in vivo fluid shearing conditions, with the degradation rate slowing down as the raw material concentration increases. The barrier retention requirements of different tissue repair cycles can be precisely matched by adjusting the raw material concentration.

[0017] Furthermore, the hydrogel exhibits excellent biocompatibility, with hemolysis rates below 5% at concentrations of 20 mg / mL, 25 mg / mL, and 30 mg / mL, meeting the blood compatibility standards for medical biomaterials. In vivo application shows no significant organ toxicity and will not cause pathological damage to major organs such as the heart, liver, spleen, lungs, and kidneys.

[0018] This invention also provides the application of the above-mentioned in-situ injectable hydrogel containing hydrazone bonds. The hydrogel, as a biomedical physical barrier material, is used to prepare a formulation for preventing postoperative abdominal adhesions after abdominal surgery. It can be injected into the surgical wound to form a gel in situ, uniformly covering irregular damaged areas and forming a stable physical isolation barrier. It effectively inhibits inflammatory cell infiltration and collagen fiber deposition, and has excellent preventive effects on mild, moderate and severe abdominal adhesions. In particular, in the severe adhesion model induced by talc combined with mechanical injury, the anti-adhesion effect is significantly better than existing products.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The in-situ injectable hydrogel preparation method of the present invention is simple, with mild reaction conditions. It can be rapidly gelled at room temperature through Schiff base reaction without the need to introduce toxic chemical crosslinking agents, thus avoiding the biotoxicity risks brought by crosslinking agents. It has good batch stability and is easy to scale up for production.

[0021] The hydrogel prepared by this invention has controllable properties. The gelation rate, swelling behavior, mechanical properties and degradation rate can be precisely adjusted by regulating the concentration of raw materials. It can meet the needs of different clinical scenarios and tissue repair cycles and has a wide range of applications.

[0022] The hydrogel prepared by this invention combines excellent injectability, self-healing properties, biodegradability and biocompatibility, and can meet the operational requirements of laparoscopic minimally invasive surgery. It can uniformly cover irregular surgical wounds, can rapidly self-heal after being mechanically damaged in vivo, and maintain the integrity of the physical barrier for a long time.

[0023] The hydrogel prepared by this invention has excellent effects in preventing abdominal adhesions. Through multiple mechanisms of action, including physical isolation of the wound, inhibition of inflammatory cell infiltration, and reduction of collagen fiber deposition, it has significant protective effects against mild, moderate, and severe abdominal adhesions induced by mechanical injury, tissue defects, and foreign bodies. In a talc-induced severe abdominal adhesion model, its anti-adhesion performance is also far superior to that of commonly used sodium hyaluronate hydrogels, and it has no obvious in vivo toxicity. It provides a safe, efficient, and convenient new solution for the prevention and treatment of abdominal adhesions after surgery, and has important clinical translational value and application prospects. Attached Figure Description

[0024] Figure 1 The images are scanning electron microscope images of the hydrogel in Example 1, with magnification of (a) × 1000 and (b) × 2000.

[0025] Figure 2 The following are rheological test diagrams of the hydrogel in Example 1: Figure (a) shows the strain performance test, Figure (b) shows the time dependence test, Figure (c) shows the viscosity and shear thinning test, and Figure (d) shows the self-healing performance test.

[0026] Figure 3 This is a diagram showing the injectability test of the hydrogel in Example 1;

[0027] Figure 4 This is a diagram of the self-healing test of the hydrogel in Example 1;

[0028] Figure 5 The swelling ratio curves are shown for hydrogels of different concentrations.

[0029] Figure 6 The degradation rate curves of hydrogels with different concentrations are shown.

[0030] Figure 7 A comparison chart of hemolysis rates for hydrogels of different concentrations;

[0031] Figure 8 The images show the gross observation of abdominal adhesions in each group of rats after surgery. Figure (a) shows the mechanical injury + abdominal wall scraping model (mild), Figure (b) shows the mechanical injury + abdominal wall defect model (moderate), and Figure (c) shows the mechanical injury + talcum powder stimulation model (severe).

[0032] Figure 9 The graph shows the adhesion scores of rats in each group in three different models of abdominal adhesion.

[0033] Figure 10 H&E staining images of major organs of rats in the blank control group and hydrogel group on the 5th day after surgery;

[0034] Figure 11The images show the pathological staining of the cecum-abdominal wall tissue of rats in each group. Figure (a) shows the mechanical injury + abdominal wall scraping model, Figure (b) shows the mechanical injury + abdominal wall defect model, and Figure (c) shows the mechanical injury + talcum powder stimulation model. Detailed Implementation

[0035] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. The described embodiments are merely some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0036] It should be noted that the terms "comprising" and "having" and any variations thereof in the specification and claims of this invention are intended to cover non-exclusive inclusion. For example, a process, method, product, or apparatus that includes a series of steps or units is not necessarily limited to those steps or units that are explicitly listed, but may include other steps or units that are not explicitly listed or that are inherent to such process, method, product, or apparatus.

[0037] The present invention will now be described in further detail with reference to the accompanying drawings:

[0038] Example 1

[0039] This embodiment prepares an in-situ injectable hydrazone hydrogel (PCA supramolecular hydrogel) using the following specific steps:

[0040] Weigh 8-arm-PEG10000-CHO, add deionized water to dissolve it completely, and obtain PEG-CHO solution; obtain PEG-HZ solution in the same way.

[0041] Use a pipette to draw up the PEG-HZ solution and quickly add it to an equal volume of PEG-CHO solution. Vortex to mix it completely and evenly. Use a syringe to draw up the solution and quickly dispense it. Allow the mixture to stand at room temperature to react and obtain PCA supramolecular hydrogel.

[0042] I. Microstructure Characterization of Hydrogel in Example 1

[0043] The PCA hydrogel prepared in Example 1 was subjected to vacuum freeze-drying, and its microstructure was observed using a scanning electron microscope. See [link to example]. Figure 1 The PCA hydrogel exhibits a uniform three-dimensional porous network framework structure with good pore connectivity, providing ample space for water molecule penetration and material exchange, which meets the structural requirements of anti-adhesion hydrogels.

[0044] II. Rheological property testing of hydrogel in Example 1

[0045] Rheological tests were performed on the PCA hydrogel of Example 1 using an Anton Paar MCR302 rheometer at 37°C. The results are shown below. Figure 2 .

[0046] Strain performance test: The critical strain value of the hydrogel is about 400%. When the strain is below the critical value, the storage modulus (G') is always greater than the loss modulus (G''), and the hydrogel is in a solid-like state dominated by elasticity. After the critical strain is exceeded, G' is less than G'', and the hydrogel is in a liquid-like state dominated by viscosity, and the network structure undergoes reversible destruction.

[0047] Time-dependent test: Under constant strain and frequency conditions, continuous monitoring showed no significant fluctuations between G' and G'', and G' was always greater than G'', proving that the PCA hydrogel can maintain a stable gel network structure for a long time.

[0048] Shear thinning test: The viscosity of the hydrogel decreases significantly with increasing shear rate, exhibiting typical shear thinning behavior, which provides a rheological basis for its clinical injection application.

[0049] Cyclic strain self-healing test: High and low strains were applied alternately for four cycles. The results showed that after each high-low strain switch, G' and G'' could quickly recover to their initial values, and maintained stable recovery ability after four cycles, proving that PCA hydrogel can quickly reconstruct its three-dimensional network structure after being damaged by external forces, and has excellent dynamic self-healing performance.

[0050] III. Injectability Test of Hydrogel in Example 1

[0051] Using a syringe, draw up the PCA hydrogel sample prepared in Example 1, and slowly and evenly push the syringe plunger to inject the sample onto the glass plate. See also Figure 3 The hydrogel can be continuously and uniformly extruded to form a complete gel body on a glass plate without breakage or dispersion, proving that PCA hydrogel has excellent injectability and can meet the injection operation requirements of clinical minimally invasive surgery.

[0052] IV. Self-healing performance test of hydrogel in Example 1

[0053] The precursor solutions for the hydrogels were divided into two groups, and methyl orange and rhodamine B were added to each group for staining, yielding yellow and pink hydrogels respectively. The two stained hydrogels were cut into semicircles, ensuring close contact between the cut surfaces, and then photographed and observed at room temperature. (See also...) Figure 4 The colors blend naturally at the interface, with no obvious fracture surface, proving that PCA hydrogel has good self-healing ability and can achieve autonomous repair of the structure after damage.

[0054] V. Swelling Performance Test of Hydrogel in Example 1

[0055] This experiment investigated the effect of different concentrations on the swelling properties of PCA hydrogels. PEG-CHO and PEG-HZ solutions with concentrations of 20 mg / mL, 25 mg / mL, and 30 mg / mL were prepared, mixed at a 1:1 volume ratio, vortexed, and allowed to stand at room temperature to form gels, resulting in PCA hydrogel samples of different concentrations. Each group of hydrogel samples was immersed in deionized water, removed at preset time points, blotted dry with filter paper, and weighed until the sample mass no longer changed. The swelling rate was calculated based on the mass change, and swelling curves were plotted.

[0056] See results Figure 5 Each group of hydrogels swelled rapidly within 0-10 hours and reached an equilibrium swelling state in about 20 hours. The swelling performance of the hydrogel is concentration-dependent; the higher the concentration, the higher the equilibrium swelling rate and the fastest swelling rate. The concentration can be adjusted to meet different clinical swelling needs.

[0057] VI. Test on the degradation rate change of hydrogel in Example 1

[0058] To investigate the effect of different concentrations on the in vitro degradation performance of PCA hydrogels, each group of hydrogel samples was immersed in deionized water and placed in a constant temperature shaker to simulate the in vivo fluid shear environment. The samples were taken out at preset time points, the surface moisture was absorbed with filter paper and weighed until the samples were completely degraded. The degradation rate was calculated and degradation curves were plotted.

[0059] See results Figure 6 The degradation rate of each group of hydrogels continuously increased over time, eventually achieving 100% complete degradation. The degradation rate was concentration-dependent; the lower the concentration, the faster the degradation rate, while the higher the concentration, the slower the degradation rate in the early stages. This demonstrates that the in vivo retention time of hydrogels can be precisely adjusted by controlling the concentration of raw materials, thus matching the barrier requirements of different tissue repair cycles.

[0060] VII. Hemolytic Properties Test of Hydrogel in Example 1

[0061] Fresh whole blood was collected from SD rats, and red blood cells were separated by centrifugation to prepare red blood cell suspensions. The experiment was divided into a positive control group (distilled water), a negative control group (physiological saline), and PCA hydrogel experimental groups with concentrations of 20 mg / mL, 25 mg / mL, and 30 mg / mL. The extracts from each group were mixed with the red blood cell suspension in equal volumes, incubated at 37°C, centrifuged, and the supernatant was collected. The absorbance was measured using a UV-Vis spectrophotometer, and the hemolysis rate of each group was calculated.

[0062] See results Figure 7The hemolysis rates of the PCA hydrogel experimental groups at concentrations of 20 mg / mL, 25 mg / mL, and 30 mg / mL were all below 5%, which meets the national standard for blood compatibility of medical biomaterials. Among them, the hemolysis rate of the 20 mg / mL group was close to that of the negative control group, the hemolysis rate of the 25 mg / mL group was about 2%, and the hemolysis rate of the 30 mg / mL group was about 4%, which proves that the PCA hydrogel does not cause significant damage to red blood cells and has excellent blood compatibility and biosafety.

[0063] VIII. Test of the anti-sticking effect of hydrogel in Example 1

[0064] This embodiment uses a rat model of abdominal adhesions to investigate the in vivo efficacy of PCA hydrogel in preventing postoperative abdominal adhesions.

[0065] 1. Laboratory animals and grouping

[0066] SPF-grade male SD rats, weighing 250g±20g, were selected. Twenty rats were included in each type of intraperitoneal adhesion model and randomly divided into four groups (n=5): blank control group (Control group, no treatment), model group (Model group, no intervention after modeling), PCA hydrogel group (PCA group, 25mg / mL PCA hydrogel injected intraperitoneally after modeling), and positive control group (HA group, commercially available sodium hyaluronate hydrogel injected after modeling).

[0067] 2. Construction of a peritoneal adhesion model

[0068] Three different severity rat models of abdominal adhesions were constructed to cover mild, moderate and severe clinical adhesion scenarios: (1) Mechanical injury combined with abdominal wall scraping model (mild): After rats were anesthetized with isoflurane, the abdomen was prepared and disinfected, an incision was made in the midline of the abdomen, the cecum was removed, and the cecum serosal surface was repeatedly wiped with sterile gauze until punctate bleeding occurred; the peritoneum and muscle layer were scraped off the abdominal wall with a scalpel to form an abdominal wall scraping wound; the cecum was sutured to the abdominal wall wound with absorbable sutures to ensure close contact of the injured wound, the PCA group and HA group were injected with the corresponding sample to evenly cover the wound, the abdominal wall was sutured layer by layer, and penicillin was injected subcutaneously after the operation to prevent infection. (2) Mechanical injury combined with abdominal wall defect model (moderate): On the basis of the above operation, the full-thickness tissue of the abdominal wall was removed to form an abdominal wall defect, and the rest of the operation was the same as before. (3) Mechanical injury combined with talcum powder stimulation model (severe): After wiping the cecum until bleeding, talcum powder is evenly applied to the serosal surface to induce a severe inflammatory response and fibrosis. The rest of the operation is the same as before.

[0069] 3. Evaluation of therapeutic effect

[0070] On the fifth day after surgery, the rats were euthanized and the following indicators were tested: (1) Gross observation and adhesion score: A double-blind method was used to standardize the score according to the degree of abdominal adhesion. The results are shown in [reference]. Figure 8 and Figure 9In all three models, rats in the Model group showed severe intra-abdominal adhesions, with the cecum tightly adhered to the abdominal wall tissue and difficult to separate; the degree of adhesion in the HA group was reduced, but significant adhesions still existed, and the protective effect was limited; rats in the PCA group had almost no intra-abdominal adhesions, and the morphology of the damaged peritoneum basically returned to normal, with a significantly better anti-adhesion effect than the Model and HA groups, and even in the talc-induced severe inflammation model, it still showed excellent adhesion protection.

[0071] (2) In vivo organ toxicity evaluation: Heart, liver, spleen, lung, and kidney tissues were collected from rats in the Control and PCA groups and subjected to H&E staining. The results are shown in [reference needed]. Figure 10 In both the PCA and Control groups, no significant pathological abnormalities were observed in the major organs of the rats. The cardiomyocytes were neatly arranged, the hepatic cord structure was normal, and the spleen, lung, and kidney tissues were intact with no inflammatory cell infiltration or tissue damage. This demonstrates that the in vivo application of PCA hydrogel has no significant organ toxicity and good biosafety.

[0072] (3) Histopathological examination: Cecal-abdominal wall adhesion tissues were collected from each group of rats and subjected to H&E staining and Masson staining. The results are shown in [reference]. Figure 11 In the Model group, the cecum was closely attached to the abdominal wall tissue with no clear boundary, and there was extensive proliferation of connective tissue, accompanied by significant inflammatory cell infiltration and collagen fiber deposition. In the HA group, inflammation and collagen deposition were reduced, but significant connective tissue proliferation was still present. In the PCA group, the cecum was completely separated from the abdominal wall tissue, with no significant connective tissue proliferation, inflammatory cell infiltration, or collagen fiber deposition, and the damaged tissue showed good repair. Histologically, this demonstrated the excellent effect of PCA hydrogel in preventing abdominal adhesions.

[0073] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A method for preparing an injectable hydrogel with in-situ hydrazone bonds to prevent intra-abdominal adhesions, comprising the following steps: 1) Dissolve 8-arm-PEG10000-CHO and 8-arm-PEG10000-HZ in deionized water to obtain PEG-CHO solution and PEG-HZ solution respectively. 2) Add the PEG-HZ solution to the PEG-CHO solution at a volume ratio of 1:1, vortex mix, and allow to stand at room temperature to react, thus obtaining an in-situ injectable hydrazone hydrogel, namely PCA supramolecular hydrogel.

2. The method for preparing the hydrogel according to claim 1, characterized in that, The concentrations of both the PEG-CHO solution and the PEG-HZ solution are 20-30 mg / mL.

3. In the method for preparing hydrogel according to claim 1, the vortex mixing time in step 2) is 15-30s.

4. According to the preparation method of claim 1, the molecular weight of both 8-arm-PEG10000-CHO and 8-arm-PEG10000-HZ is 10000.

5. An in-situ hydrazone-bonded injectable hydrogel prepared by the preparation method according to any one of claims 1-4, characterized in that, The hydrogel is a three-dimensional porous supramolecular hydrogel constructed by cross-linking hydrazone bonds between 8-arm-PEG10000-CHO and 8-arm-PEG10000-HZ through a Schiff base reaction.

6. The in-situ injectable hydrogel with hydrazone bonds according to claim 5, characterized in that, The hydrogel exhibits shear-thinning properties, with its viscosity decreasing significantly with increasing shear rate. Under alternating cycles of high and low strain, its storage modulus and loss modulus can rapidly recover to their initial values.

7. The in-situ injectable hydrogel with hydrazone bonds according to claim 5, characterized in that, The hydrogel has self-healing properties, and the interface can be fused after the cut surfaces are bonded together. It can be continuously and evenly extruded through a syringe and has excellent injectability.

8. The in-situ injectable hydrogel with hydrazone bonds according to claim 5, wherein the hydrogel is completely degradable in a simulated in vivo environment, and the degradation rate can be controlled by the raw material concentration. When the concentration is 20-30 mg / mL, the hemolysis rate is less than 5%, and it has excellent biocompatibility.

9. The application of the in-situ hydrazone-injectable hydrogel according to claim 5, characterized in that, As a biomedical physical barrier material, it is used to prepare formulations for preventing postoperative abdominal adhesions after abdominal surgery.

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