CN116785266A - Novel medicine for preventing postoperative abdominal adhesion and preparation method thereof - Google Patents

Abstract

The invention provides a novel drug for preventing postoperative abdominal adhesion and a preparation method thereof, which belongs to the technical field of postoperative abdominal adhesion treatment. The drug includes the following raw materials by weight: 20-50 parts of PLA nanoparticles and 15-35 parts of honokiol. , 10-30 parts of sodium hyaluronate. The present invention aims to explore the formation mechanism of postoperative abdominal adhesion and develop drugs to prevent postoperative abdominal adhesion, thereby effectively reducing the pain of patients after abdominal surgery and increasing the patient's sense of social belonging after abdominal surgery. The present invention It has important social significance and application prospects.

Description

A new type of drug for preventing postoperative abdominal adhesions and its preparation method

Technical field

The invention belongs to the technical field of postoperative abdominal adhesion treatment, and specifically relates to a novel drug for preventing postoperative abdominal adhesion and a preparation method thereof.

Background technique

Postoperative abdominal adhesions are one of the common complications after abdominal surgery. About 90-95% of patients undergoing abdominal surgery will develop postoperative abdominal adhesions. The abnormal adhesion bands formed can cause a series of related complications. Related complications, including intestinal obstruction, chronic abdominal pain, female infertility, constipation, etc., not only increase the difficulty of re-abdominal surgery and the possibility of side injuries, but also increase the patient's additional medical expenses. Currently, for postoperative abdominal There are no effective drugs for the treatment of adhesions except surgical release. However, surgery will cause more serious adhesions. Therefore, it is necessary to prevent postoperative abdominal adhesions. However, there is currently a lack of research on the key molecular mechanisms of the formation of postoperative abdominal adhesions. , especially the lack of effective molecular targets. Therefore, it is necessary to continue to actively explore the formation mechanism of postoperative abdominal adhesions and clarify the potential molecular mechanisms of postoperative abdominal adhesion formation.

The formation of postoperative abdominal adhesions is a very complex biological process, which involves many molecules and signaling pathways. After the local peritoneal tissue is damaged, the damaged area will stimulate an inflammatory response, release a large number of inflammatory cells and inflammatory molecules, and then a large number of The exuded fibrin-rich fluid and local clots will form thin adhesions locally (within 3-5 days after surgery). When adhesions are formed, both the fibrogenesis and fibrinolytic systems are activated, and the activated fibrinolytic system The fibrous tissue formed can be partially degraded, but then a large number of fibroblasts secrete different types of collagen, resulting in the formation of strong adhesion bands (5-7 days after peritoneal injury), during which the peritoneal mesothelial cells will repair the damage. Peritoneal tissue at the site (within 24 hours after surgery), but if the local tissue is blocked by fibrous tissue, peritoneal mesothelial cells will cover the surface of the local fibrous tissue to form stable adhesions. In addition, in the adherent tissue, peritoneal mesothelial cells will Under the action of inflammatory factors, they transform into fibroblasts and promote the formation of adhesions.

Based on the mechanism of postoperative abdominal adhesion formation, the current main measures to prevent postoperative abdominal adhesion formation are as follows:

1. Reduce surgical trauma and refine surgical operations;

2. Use physical barriers to isolate damaged wounds;

3. Inhibit inflammatory response and its expansion;

4. Promote the activation of fiber dissolving system;

5. Inhibit oxidative stress response;

6. Promote peritoneal repair, etc. However, considering the safety and drug accessibility for abdominal patients after surgery, the current drugs to prevent postoperative abdominal adhesion are mainly physical barrier isolation drugs, which have limited effect. The reason is that the role of peritoneal mesothelial cells in peritoneal repair has been ignored;

At present, there is a lack of key molecular mechanisms in peritoneal repair and drugs to intervene in postoperative abdominal adhesions based on the above theory. Therefore, it is necessary to further actively explore the formation process of postoperative abdominal adhesions and develop new drugs.

Contents of the invention

The purpose of the present invention is to provide a novel drug for preventing postoperative abdominal adhesion and a preparation method thereof. The present invention aims to explore the formation mechanism of postoperative abdominal adhesion and develop a drug for preventing postoperative abdominal adhesion, thereby effectively reducing the pain of patients after abdominal surgery and increasing the This invention has important social significance and application prospects for patients' sense of social belonging after abdominal surgery.

In order to achieve the above objects, the present invention provides the following technical solutions:

A new type of drug for preventing postoperative abdominal adhesions, including the following raw materials in parts by weight:

20-50 parts of PLA nanoparticles, 15-35 parts of honokiol, and 10-30 parts of sodium hyaluronate.

As a preferred solution of the present invention, a new drug for preventing postoperative abdominal adhesions includes the following raw materials in parts by weight:

30-40 parts of PLA nanoparticles, 20-30 parts of honokiol, and 15-25 parts of sodium hyaluronate.

As a preferred solution of the present invention, a new drug for preventing postoperative abdominal adhesions includes the following raw materials in parts by weight:

35 parts of PLA nanoparticles, 25 parts of honokiol, and 20 parts of sodium hyaluronate.

A ddd method for preparing a new drug for preventing postoperative abdominal adhesion, including the following steps:

S1. Preparation of nanomaterials: Nanomaterials are prepared based on PLA nanoparticles and honokiol;

S2. Preparation of extracellular matrix metalloenzyme-responsive hydrogel: synthesize nanomaterials and sodium hyaluronate to finally prepare extracellular matrix metalloenzyme-responsive hydrogel.

Compared with the prior art, the beneficial effects of the present invention are:

The present invention aims to explore the formation mechanism of postoperative abdominal adhesion and develop drugs to prevent postoperative abdominal adhesion, thereby effectively reducing the pain of patients after abdominal surgery and increasing the patient's sense of social belonging after abdominal surgery. The present invention has important social significance and application prospects.

Description of the drawings

The drawings are used to provide a further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention. In the attached picture:

Figure 1 is a flow chart of the present invention;

Figure 2 is a diagram of the molecular mechanism of Sirt3 inhibiting oxidative stress in the present invention;

Figure 3 is a schematic diagram of the effect of sodium hyaluronate-coated PLA honokiol nanohydrogel on inhibiting postoperative abdominal adhesion in the present invention;

Figure 4 is the first technical roadmap in the present invention;

Figure 5 is a second technical roadmap in the present invention;

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments can be obtained by those of ordinary skill in the art without making creative efforts. , all belong to the protection scope of the present invention.

Example 1:

A new type of drug for preventing postoperative abdominal adhesion, including the following raw materials by weight: 20 parts of PLA nanoparticles, 15 parts of honokiol, and 10 parts of sodium hyaluronate;

There are many mechanisms for the formation of abdominal adhesions after surgery. Oxidative stress injury is the key to the formation of adhesions caused by peritoneal injury. Oxidative stress reaction refers to the imbalance in the production and removal of reactive oxygen species in the body, resulting in the accumulation of a large amount of reactive oxygen species and causing local tissue damage. Injury. After surgery, local abdominal tissue is damaged, resulting in the recruitment of a large number of inflammatory cells. Locally damaged cells and a hypoxic environment will release a large amount of reactive oxygen species, including O2–, H2O2, HO-, HOCl, etc. These reactive oxygen species may cause apoptosis and necrosis of local cells, especially peritoneal mesothelial cells, key cells for peritoneal repair, causing amplification of local inflammatory responses, and further leading to fibrosis and peritoneal mesothelial cell-to-interstitial transformation. Therefore, it is important to reduce oxidative stress damage. The key link to inhibit the formation of postoperative abdominal adhesions;

Please refer to Figure 2. Sirt3 is a class III deacetylase in the body that relies on nicotinamide purine dinucleotide. This molecule has two molecular weights, one is 43kD and is mainly distributed in mitochondria, and the other is 28kD. By carrying out histone acetylation modification, Sirt3 plays an extremely important role in the body. It can protect mitochondrial function, change energy metabolism, reduce oxidative stress, promote autophagy, inhibit fibrosis formation, etc. Studies have shown that Sirt3 plays an important role in tissue repair. It can play a wide range of roles in the process and can reduce oxidative stress damage through a variety of ways. It can modify the reactive oxygen species scavenging substance SOD through deacetylation, enhance its enzyme activity, and reduce mitochondrial oxidative stress damage; it can also activate LKB1 /AMPK pathway protects mitochondrial function and promotes mitochondrial fusion. Secondly, Sirt3 can reduce fibrosis formation, inhibit the expression of HIF1α under hypoxia, regulate the TGF-β1/Smads pathway activity and inhibit fibrosis formation. Due to the postoperative abdominal cavity In the process of adhesion formation, fibrosis formation and oxidative stress play a crucial role, and Sirt3 can inhibit oxidative stress response and fiber formation through multiple pathways at the same time, suggesting that Sirt3 can be used as a target to prevent postoperative abdominal adhesion formation. Click for further research;

Honokiol is an extract of the traditional Chinese medicine Magnolia officinalis. As an agonist of Sirt3, honokiol can reduce tissue oxidative stress damage and promote tissue repair through various pathways. Honokiol can reduce β-amyloid Protein expression alleviates the symptoms of Alzheimer's disease, reduces renal inflammation and fibrosis induced by unilateral ureteral obstruction by regulating mitochondrial dynamics and the renal NF-κB-TGF-β1/Smads signaling pathway, and reduces cerebral ischemic damage. Reduce cardiotoxic damage and myocardial hypertrophy, etc. Honokiol can reduce oxidative stress damage and inhibit postoperative abdominal adhesion formation by activating Sirt3. However, since honokiol is a natural plant extract, its solubility is further restricted. Clinical application, and due to the spatial blocking effect caused by local adhesion tissue during the formation of adhesions, its effect is relatively limited. Therefore, the dosage form is further changed and a new drug based on honokiol is developed, which is very useful for the prevention and treatment of postoperative abdominal adhesions. favorable;

Polylactic acid (polylactic acid, PLA) is also called polylactide, that is, PLA nanoparticles are polyester polymerized with lactic acid as raw material. PLA nanoparticles are a non-toxic, non-irritating synthetic polymer material with excellent biological properties. Degradability, compatibility and absorbability are currently widely used in the preparation of nanomaterials. PLA nanoparticles can achieve good water solubility, especially nanomaterials prepared by PLA nanoparticles and honokiol are lipid-soluble. The drug is particularly advantageous and can help the absorption and release of the drug. The present invention uses PLA nanoparticles and honokiol to prepare nanomaterials, which improves its hydrophilicity. However, due to the early leakage of fibers after peritoneal damage, For the spatial barrier effect caused by substances, the simple use of PLA nanoparticles and honokiol is effective, and its mode of action needs to be further improved to enhance its role in preventing postoperative abdominal adhesion;

Hydrogel is a type of extremely hydrophilic three-dimensional network structure gel. It swells rapidly in water and can maintain a large volume of water without dissolving in this swollen state. The solid behavior of the gel can be maintained under certain conditions. With a certain shape and volume, the liquid behavior is that solutes can diffuse or penetrate from the hydrogel. As a new type of material, hydrogel can not only isolate damaged wounds through physical barriers, but can also be coated with different drugs to promote tissue growth. Healing and inhibiting tissue oxidative stress damage, especially bioresponsive hydrogels, which can slowly degrade with the action of special enzymes in the tissue, are particularly suitable for use in the prevention of postoperative abdominal adhesions, and can not only It provides a potential time window for peritoneal mesothelial cell repair, and can also gradually degrade and release the contained drugs over time. It has good biocompatibility and does not affect the function of abdominal tissue. Sodium hyaluronate is a kind of glucuronic acid, which has no species specificity. It is widely present in placenta, amniotic fluid, lens, articular cartilage, skin dermis and other tissues; in organs, it is distributed in the cytoplasm and interstitium of cells. , which lubricates and nourishes the cells and cell organs themselves. Sodium hyaluronate has good tissue compatibility and is widely used in material preparation. Metalloenzyme MMPs in tissues can degrade sodium hyaluronate through various pathways. There have been many studies on preparing it into MMPs enzyme-responsive water. gel;

The present invention first prepares nanomaterials through PLA nanoparticles and honokiol, then synthesizes sodium hyaluronate and the above-mentioned nanomaterials, and then makes an extracellular matrix metalloenzyme-responsive hydrogel, and realizes physical barrier isolation through the hydrogel material. The damaged wound surface is encapsulated with the target drug, while PLA nanoparticles can increase the bioabsorbability of the drug. The successfully prepared nanomaterials and honokiol contribute to the solubility of honokiol in tissues, which is beneficial to It exerts a biological effect to enable the use of drugs that promote peritoneal repair on the basis of physical barrier isolation.

Example 2:

A new type of drug for preventing postoperative abdominal adhesion, including the following raw materials by weight: 30 parts of PLA nanoparticles, 20 parts of honokiol, and 15 parts of sodium hyaluronate.

Example 3:

A new type of drug for preventing postoperative abdominal adhesion, including the following raw materials by weight: 35 parts of PLA nanoparticles, 25 parts of honokiol, and 20 parts of sodium hyaluronate.

Example 4:

A new type of drug for preventing postoperative abdominal adhesion, including the following raw materials by weight: 40 parts of PLA nanoparticles, 30 parts of honokiol, and 25 parts of sodium hyaluronate.

Example 5:

A new type of drug for preventing postoperative abdominal adhesion, including the following raw materials by weight: 52 parts of PLA nanoparticles, 35 parts of honokiol, and 30 parts of hyaluronic acid.

Example 6:

Please refer to Figure 1. This embodiment provides a new method for preparing a drug for preventing postoperative abdominal adhesion, which includes the following steps:

S1. Preparation of nanomaterials: Nanomaterials are prepared based on PLA nanoparticles and honokiol;

S2. Preparation of extracellular matrix metalloenzyme-responsive hydrogel: synthesize nanomaterials and sodium hyaluronate to finally prepare extracellular matrix metalloenzyme-responsive hydrogel.

Example 7:

This example is based on the drugs prepared in Examples 1-7. It is intended to further verify the technical effects of the present invention through in vivo animal experiments and in vitro cell experiments, thereby providing new drugs for the prevention and treatment of postoperative abdominal adhesions, and further enriching the formation mechanism of postoperative abdominal adhesions. ;

(1) The role and mechanism of Sirt3 in postoperative abdominal adhesion:

① Establishment of mouse postoperative abdominal adhesion model and adhesion scoring:

The cecum scraping and rubbing method was used to create a model. The method is as follows: After the mouse is successfully anesthetized, place it in a supine position, remove the midline opening of the abdomen, which is about 2cm long, lift out the cecum, and rub the intestinal wall with dry gauze about 30 times until it reaches a needle-like bleeding point. The same method is used. Rub the abdominal wall until bleeding, place the damaged cecum and abdominal wall relative to each other, and close the abdomen layer by layer. At different time points after the operation (days 1, 3, 5, 7, and 14 after the operation), the rats are anesthetized again, and the rats are taken. An inverted "U"-shaped incision was made in the lower abdomen. The degree of adhesion is scored using Nair's scoring system: no adhesion between the abdominal wall and the cecum is scored as 0 points; an adhesion band between the abdominal wall and the cecum or between the cecum and the cecum is scored as 1 point; there is an adhesion band between the abdominal wall and the cecum or between the abdominal organs. Two adhesion bands are scored as 2 points; two or more adhesion bands between the abdominal wall and cecum or between abdominal organs are scored as 3 points; the cecum is directly adhered to the abdominal wall, the adhesions are dense, and the adhesion bands cannot be evaluated, and the adhesion bands cannot be evaluated are scored as 4 points; The mouse adhesion-free rate is the total number of mice in each group of mice that have no adhesion. The present invention has matured to construct this model. Please refer to Figure 3 for details;

②Construct Sirt3 gene knockout mice:

C57BL/6N-Sirt3em1cyagen has already been constructed and molded, which can be purchased and then propagated and identified in our laboratory;

③Expression of Sirt3 in postoperative abdominal adhesion tissue:

A mouse postoperative abdominal adhesion model was created by cecal scraping. The mice were sacrificed on the 1st, 3rd, 5th, and 10th day after surgery, and the normal peritoneum and peritoneal tissue from the corresponding adhesion site were harvested. The tissue was further subjected to immunohistochemical staining. Immunofluorescence staining (keratin 19-labeled peritoneal mesothelial cells and Sirt3 were immunofluorescently stained at the same time) to detect the expression of Sirt3 in peritoneal tissue and peritoneal mesothelial cells at different time periods;

④ To detect the effect and molecular mechanism of Sirt3 knockout on postoperative abdominal adhesion formation in mice

The normal group of mice, the C57BL/6N-Sirt3 control group, and the C57BL/6N-Sirt3 gene knockout mice were modeled using the cecal scraping method, and the effect of knocking out Sirt3 on the formation of adhesions in mice was tested through Nair's scoring system. The effects of knocking out Sirt3 on inflammatory response, fibrosis and peritoneal repair in mice were detected through HE staining, Sirius red staining, immunohistochemical staining for α-SMA/CK19, immunofluorescence staining for ROS, and ELISA for MDA/SOD/GSH;

(2) Honokiol reduces the formation of postoperative abdominal adhesions by activating Sirt3 to inhibit oxidative stress response (please refer to the first technical roadmap in the present invention, namely Figure 4):

①Animal model and grouping: The cecal scraping method was used to create a model, and 40 rats were randomly divided into 5 groups, with 8 rats in each group. The sham operation group only underwent laparotomy, and the control group underwent cecal scraping method to create a model. The sodium hyaluronate group used sodium hyaluronate gel to smear the damaged wounds, and the high and low honokiol treatment groups were given different doses of honokiol after surgery. The rats were killed after 7 days, and the rats in different groups were evaluated by Nair's score. Abdominal adhesions, and remove peritoneal adhesion tissue or normal peritoneal tissue for further testing;

② Inflammation response detection: Use HE staining to detect tissue morphology and inflammatory response, and further use ELISA to detect IL-6, IL-1β, TGF-β1, etc. in the adhesion tissue to clarify the tissue inflammatory response;

③ Detection of oxidative stress-related indicators: The level of reactive oxygen species in the tissue is detected by ROS staining on frozen sections, and the levels of MDA, GSH, SOD, etc. in the adhesion tissue are further detected by ELISA;

④ Detect the expression of Sirt3 in the tissue through immunohistochemical staining, and further detect the peritoneal repair status through immunohistochemical staining for CK19;

⑤Construct and culture the human peritoneal mesothelial cell stromal strain HMrSV5, and detect the protective effect of peritoneal mesothelial cells on H2O2-induced oxidative stress damage after the action of honokiol, including flow cytometry to detect cell apoptosis and oxidative stress. Stimulus-related levels of ROS/MDA/GSH/SOD, etc., Westernbolt detection of apoptosis-related protein levels, and further detection of Sirt3 expression;

(3) Research on the effect and mechanism of sodium hyaluronate-coated PLA honokiol nanohydrogel on inhibiting postoperative abdominal adhesion formation and its mechanism (please refer to the second technical roadmap in the present invention, namely Figure 5):

①Material synthesis: First, honokiol is prepared into nanoparticles by coating it with PLA, and then its physical properties are further tested, including cytotoxicity, solubility, release rate, etc.; the prepared PLA is further coated with sodium hyaluronate gel. Prepare the nanoparticles into hydrogels and detect the release rate of honokiol in the material, material toxicity, stiffness, etc.;

② In vivo animal experiments to detect the biological effects of new materials: 48 rats were randomly divided into 6 groups. The sham operation group only underwent abdominal opening surgery, the control group used cecal scraping method to create a model without any treatment, and the sodium hyaluronate group used hyaluronic acid The sodium acid treatment and honokiol treatment groups were treated with honokiol, the PLA-coated honokiol treatment group was treated with PLA honokiol particles dissolved in water, and the hydrogel group was treated with synthetic enzyme-responsive hydrogel. Glue treatment, the same as above, the mice were sacrificed after 7 days, and the adhesion formation was evaluated using Nair's score, and peritoneal tissue was further taken for the next step of testing;

③Detection of inflammatory response: Same as before;

④ Detection of oxidative stress related indicators: Same as before;

⑤ Detection of oxidative stress related indicators: Same as before;

⑥Detect the expression of Sirt3 in the tissue through immunohistochemical staining, and further detect the peritoneal repair status through immunohistochemical staining for CK19;

⑦ Material degradation and toxicity testing: Bury the synthesized hydrogel material under the skin, and detect the degradation of the hydrogel after different periods of time. The liver and spleen of different groups of rats were taken from the material group and the control group, and liver toxicity was detected by HE staining;

⑧Cell biology experiments: Culture the human peritoneal mesothelial cell interstitial strain HMrSV5, and use different concentrations of enzyme-degraded hydrogels and PLA-coated honokiol particles to detect the effect of the new material on the peritoneal mesentery after H2O2-induced oxidative stress damage. The protective effect of skin cell oxidation, including cell apoptosis, cellular oxidative stress, etc.;

At present, most methods for postoperative abdominal adhesions are mainly based on simple physical barrier isolation, and their effects are effective. The main reason is that the role of peritoneal repair in adhesion formation is ignored, especially the role of peritoneal mesothelial cell repair; the present invention The theory is proposed that adding honokiol, a drug that promotes peritoneal repair, on the basis of sodium hyaluronate hydrogel isolation will help prevent the formation of postoperative abdominal adhesions at different levels and through different mechanisms. Currently, there are few relevant Research report, this is the theoretical innovation of the present invention;

Although there are numerous studies on the role and mechanism of new materials in the prevention and treatment of postoperative abdominal adhesions, relevant drugs based on the Sirt3 target have not yet been reported; in addition, PLA-coated honokiol nanomaterials and hyaluronic acid There are few studies on the application of sodium hydrogel in postoperative abdominal adhesion. The present invention combines two new materials in order to promote the orderly repair of the peritoneum. There are no relevant reports on this method so far. This is the innovation of the method of the present invention. ;

The formation of postoperative abdominal adhesions is a complex biological process involving many molecular mechanisms. In this study, we preliminarily explored the role of Sirt3 in the formation of postoperative abdominal adhesions, especially its role in reducing oxidative stress damage. There are currently no relevant reports. This is the innovation of the molecular mechanism of the present invention;

Economic benefits of the invention:

Postoperative abdominal adhesion is a common complication after surgery. Preventing postoperative abdominal adhesion is a necessary step after almost all abdominal operations. Currently, commonly used drugs to prevent the formation of postoperative abdominal adhesion have limited effects. The present invention intends to develop a new Drugs for preventing postoperative abdominal adhesions will have a broad market and substantial economic benefits if they can be successfully applied clinically.

Social benefits of the invention:

Postoperative abdominal adhesions occur in almost all patients after abdominal surgery. Postoperative abdominal adhesions can cause a series of related complications, including chronic abdominal pain, female infertility, intestinal obstruction, constipation and difficulty in reoperation, etc. These complications The development of the disease will not only increase the patient's surgical pain, but also increase additional medical expenses and pose a serious threat to people's health; therefore, the present invention intends to explore the formation mechanism of postoperative abdominal adhesions and develop a new drug to prevent postoperative abdominal adhesions, aiming to Reducing the pain of patients after abdominal surgery and increasing their sense of social belonging after abdominal surgery have important social significance and application prospects;

Analysis of the promotion and application prospects of the present invention:

The incidence of postoperative abdominal adhesion is extremely high, and the complications caused cause a series of pain to patients. Therefore, it is necessary to actively explore its prevention and treatment methods. Preventing postoperative abdominal adhesions after abdominal surgery is almost a necessary link, so the implementation of the present invention has important social significance. If the present invention is successfully implemented, it will help develop new drugs for preventing postoperative abdominal adhesions and has broad application prospects.

Finally, it should be noted that the above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, it is still The technical solutions described in the foregoing embodiments may be modified, or some of the technical features may be equivalently replaced. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims (4)

1. A new type of drug for preventing postoperative abdominal adhesion, which is characterized in that it includes the following raw materials in parts by weight: 20-50 parts of PLA nanoparticles, 15-35 parts of honokiol, and 10-30 parts of sodium hyaluronate. 2. A new type of drug for preventing postoperative abdominal adhesion according to claim 1, characterized in that it includes the following raw materials in parts by weight: 30-40 parts of PLA nanoparticles, 20-30 parts of honokiol, and 15-25 parts of sodium hyaluronate. 3. A novel drug for preventing postoperative abdominal adhesion according to claim 2, characterized in that it includes the following raw materials in parts by weight: 35 parts of PLA nanoparticles, 25 parts of honokiol, and 20 parts of sodium hyaluronate. 4. The method for preparing a novel drug for preventing postoperative abdominal adhesion according to any one of claims 1-3, characterized in that it includes the following steps: S1. Preparation of nanomaterials: Nanomaterials are prepared based on PLA nanoparticles and honokiol; S2. Preparation of extracellular matrix metalloenzyme-responsive hydrogel: synthesize nanomaterials and sodium hyaluronate to finally prepare extracellular matrix metalloenzyme-responsive hydrogel.