Mucous membrane protuberance agent for submucosal separation and preparation method and application of mucous membrane protuberance agent

Abstract

The invention relates to a mucous membrane uplift agent for submucosal separation as well as a preparation method and application thereof. The mucous membrane uplift agent contains a gelatinizing agent, recombinant collagen and poloxamer. The mucous membrane uplift agent provided by the invention is a liquid with relatively low viscosity at room temperature, is beneficial to injection and has a temperature-sensitive phase change effect, and after the mucous membrane uplift agent is injected under the mucous membrane of an affected part of a patient, a liquid injection substance is quickly converted into a gel state under the influence of temperature, and the fluidity is reduced, so that the accumulation of the uplift agent is facilitated, and the uplift height of the mucous membrane is increased; and a safer operation space is created for the digestive tract mucosa dissection operation. The mucous membrane protuberance agent has degradability, so that the wound surface after the diseased mucous membrane is cut off can not be additionally treated, and the residual gel can be degraded or fall off after a certain period of time; meanwhile, the formed gel has a certain wound surface protection capability before falling off or degradation, and can provide protection for the wound surface within a certain time.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and in particular to a mucosal lifting agent for submucosal layer separation, and a preparation method and application thereof. Background Art

[0002] Endoscopic mucosal dissection (ESD) / endoscopic mucosal resection (EMR) refers to a minimally invasive technique that completely dissects / removes the diseased mucosa from the submucosa under an endoscope. Early gastrointestinal lesions are mainly located in the mucosa and submucosa. Since ESD / EMR can remove larger lesions with a complete lesion resection rate of over 90%, and it can also obtain pathological diagnostic samples, ESD / EMR has become the main diagnosis and treatment method for early gastrointestinal lesions.

[0003] Conventional ESD / EMR procedures typically involve injecting air or glucose solution into the submucosal layer to separate the mucosa and elevate the lesion. However, due to the fluidity of the injected material, this approach can easily cause morphological changes in the elevated area during surgery, such as a lowering of the elevation. Alternatively, the injected material can be lost during wound incision, leading to loss of the elevated effect. This can hinder surgical progress and increase surgical risk.

[0004] In recent years, some medical devices used to assist with mucosal separation procedures, such as mucosal separation fluids, have typically exhibited low viscosity, easily escaping from the dissection wound or wound surface. Furthermore, they often lack protective properties or require additional procedures or fixatives to achieve their intended purpose. This results in a longer recovery period for patients, impacting their quality of life. Furthermore, these additional procedures increase the number of surgical steps, prolonging the procedure time and increasing surgical risk.

[0005] CN114949377A discloses a submucosal injection solution and its use in preparing an adjuvant for endoscopic submucosal dissection. By selecting a solvent and a PDLLA-PEG-PDLLA triblock copolymer of specific types and concentrations, the submucosal injection solution has good injectability, and the injection resistance does not significantly affect the entire submucosal injection operation process. After submucosal injection, the mucosa at the injection site is significantly elevated, and a liquid cushion is well formed, which does not show a significant decrease over time, and has good safety.

[0006] In summary, providing a preparation for assisting mucosal separation during ESD / EMR surgery has become one of the urgent problems to be solved in this field. Summary of the Invention

[0007] To solve the above technical problems, the present invention provides a mucosal lifting agent for submucosal separation surgery, a preparation method and an application thereof. The mucosal lifting agent is a liquid with low viscosity at room temperature, which is conducive to injection. After being injected into the submucosal layer, it forms a hydrogel in situ at body temperature, providing a more stable lifting effect.

[0008] To achieve this object, the present invention adopts the following technical solutions:

[0009] In a first aspect, the present invention provides a mucosal lifting agent for submucosal layer separation, wherein the mucosal lifting agent contains a gelling agent, recombinant collagen and poloxamer.

[0010] The present invention is based on the purpose of improving surgical operation procedures, improving surgical efficiency, simplifying related operating procedures, reducing surgical difficulty and reducing the risk of additional trauma, and provides a mucosal lifting agent for submucosal separation. The mucosal lifting agent is a liquid with low viscosity at room temperature, which is conducive to injection. After being injected into the submucosal layer, it forms a hydrogel in situ at body temperature, providing a more stable lifting effect. In addition, the mucosal lifting agent is degradable, and the wound surface after resection of the diseased mucosa does not need additional treatment. The residual gel will degrade or fall off after a certain period of time, so it can also be used for wounds that require titanium clip closure. The remaining hydrogel provides a more suitable environment for wound recovery within a certain period of time, which is beneficial to the proliferation of wound cells, promotes wound repair, and shortens the course of the disease.

[0011] Preferably, the gelling agent includes any one of sodium hyaluronate, sodium polyglutamate, polylysine hydrochloride or sodium alginate, or a combination of at least two thereof.

[0012] Preferably, the molecular weight of the gelling agent is 200-1800 kDa (for example, 200 kDa, 300 kDa, 500 kDa, 750 kDa, 1000 kDa, 1250 kDa, 1500 kDa or 1800 kDa, etc.).

[0013] Preferably, the recombinant collagen includes any one of type I recombinant collagen, type II recombinant collagen or type III recombinant collagen, or a combination of at least two of them.

[0014] Preferably, the poloxamer comprises poloxamer 407 and / or poloxamer 188.

[0015] Preferably, the mucosal lifting agent contains, by mass percentage, 0.1% to 2% (for example, 0.1%, 0.2%, 0.5%, 0.7%, 1%, 1.2%, 1.5%, 1.7% or 2%) of a gelling agent, 0.1% to 1% (for example, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9% or 1%) of recombinant collagen, and 15% to 25% (for example, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25%) of poloxamer.

[0016] Preferably, the mucosal lifting agent contains sodium hyaluronate, type I recombinant collagen, type III recombinant collagen and poloxamer 407.

[0017] The sodium hyaluronate, type I recombinant collagen, and type III recombinant collagen in the present invention exhibit a synergistic effect. The composition and ratio of these substances influence the adhesion of the mucosal uplifting agent to the submucosa after gelation and also influence the phase transition temperature. Within the mass percentage range provided by the present invention, a mucosal uplifting agent with good adhesion and the ability to undergo a phase transition at body temperature can be obtained.

[0018] Preferably, the mucosal lifting agent contains, by weight percentage, 0.1% to 2% (for example, 0.1%, 0.2%, 0.5%, 0.7%, 1%, 1.2%, 1.5%, 1.7% or 2%) of sodium hyaluronate, 0.1% to 0.5% (for example, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45% or 0.5%) of hydroxypropyl ethyl ester ... Type I recombinant collagen, 0.1% to 0.5% (for example, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45% or 0.5%, etc.) type III recombinant collagen and 15% to 25% (for example, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25%, etc.) poloxamer 407.

[0019] Preferably, the mucosal lifting agent further contains a colorant.

[0020] The present invention adds a colorant to the mucosal lifting agent, so that the operator can better observe and confirm the location of the lesion area, which is convenient for intraoperative operation.

[0021] Preferably, the colorant comprises methylene blue and / or sodium indigo disulfonate.

[0022] Preferably, the content of the colorant in the mucosal protrusion agent is 0.01% to 0.1% by mass (for example, it can be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09% or 0.1%, etc.).

[0023] Preferably, the mucosal lifting agent contains, by weight percentage, 0.1% to 2% (for example, 0.1%, 0.2%, 0.5%, 0.7%, 1%, 1.2%, 1.5%, 1.7% or 2%) sodium hyaluronate, 0.1% to 0.5% (for example, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45% or 0.5%) type I recombinant collagen, 0.1% to 0.5% (for example, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45% or 0.5%) type I recombinant collagen, 0.5%, etc.) type III recombinant collagen, 15% to 25% (for example, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25%, etc.) poloxamer 407, 0.01% to 0.1% (for example, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09% or 0.1%, etc.) colorant and 0.5% to 2% (for example, 0.5%, 0.75%, 1%, 1.25%, 1.5%, 1.75% or 2%, etc.) sodium chloride, and the balance is water.

[0024] In a second aspect, the present invention provides a method for preparing the mucosal lifting agent according to the first aspect, the preparation method comprising the following steps:

[0025] (1) stirring and mixing the gelling agent solution and the poloxamer solution;

[0026] (2) adding recombinant collagen, dissolving it and stirring it to obtain the mucosal lifting agent.

[0027] Preferably, the gelling agent solution in step (1) further contains a colorant.

[0028] Preferably, step (2) further comprises adding sodium chloride, dissolving it and stirring to mix it.

[0029] Preferably, the stirring temperature is 18-25°C (for example, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C or 25°C, etc.).

[0030] The preparation method of the mucosal lifting agent provided by the present invention can effectively improve the dissolution efficiency and solution uniformity of the product and prevent gelation or agglomeration during the process.

[0031] Preferably, the preparation method specifically comprises the following steps:

[0032] (1) Dissolve poloxamer at 4-10°C to prepare stock solution A;

[0033] (2) Dissolve the gelling agent and colorant at 4-10°C to prepare stock solution B;

[0034] (3) Stir and mix stock solution A and stock solution B at 18-25°C;

[0035] (4) adding recombinant collagen, dissolving and stirring to mix evenly, and finally adding sodium chloride, dissolving and stirring evenly to prepare the mucosal lifting agent.

[0036] In a third aspect, the present invention provides a method for forming a gel of the mucosal lifting agent as described in the first aspect, the method comprising placing the mucosal lifting agent at an environment of 30 to 40°C (for example, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C or 40°C, etc.).

[0037] In a fourth aspect, the present invention provides a thermosensitive hydrogel, which is prepared by the following steps: injecting the mucosal lifting agent described in the first aspect into the submucosal layer of the digestive tract to form a hydrogel in situ at body temperature.

[0038] Preferably, the digestive tract includes any one of the esophagus, stomach or intestine, or a combination of at least two of them.

[0039] In a fifth aspect, the present invention provides use of the mucosal lifting agent as described in the first aspect or the temperature-sensitive hydrogel as described in the fourth aspect in the preparation of a preparation for assisting endoscopic mucosal dissection or endoscopic mucosal resection.

[0040] The mucosal lifting agent provided by the present invention can be mass-produced by conventional pharmaceutical equipment and can be applied to ESD / EMR surgery for early gastrointestinal cancer, submucosal tumor resection, and protection of refractory ulcer wounds.

[0041] Other specific point values within the above numerical ranges can be selected and will not be described in detail here.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] The mucosal lifting agent provided by the present invention creates a more convenient environment for doctors to operate during gastrointestinal mucosal resection, reduces the probability of accidents caused by doctors' misoperation, reduces the risk of accidents during surgery, and improves the safety level of surgery. The mucosal lifting agent has a thermosensitive phase change effect. After being injected into the submucosal membrane of the patient's affected part, the liquid injection is affected by the temperature and quickly changes to a gel state, reducing fluidity, which is conducive to the accumulation of the lifting agent, increases the height of the mucosal lifting, and creates a safer operating space for surgery. When the mucosa raised by this product is removed, the internal lifting fluid will not be lost due to the incision of the mucosa, resulting in a reduction in the lifting height, effectively reducing the risk of accidental injury to the patient caused by misoperation during the operation. DETAILED DESCRIPTION

[0044] To further illustrate the technical means and effects of the present invention, the present invention is further described below with reference to the following examples. It should be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention.

[0045] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0046] Preparation Example 1

[0047] This preparation example provides a method for preparing a mucosal lifting agent for submucosal layer separation, comprising the following steps:

[0048] (1) Dissolve poloxamer at 6°C to prepare stock solution A, and store in a refrigerator for later use.

[0049] (2) Dissolve the gelling agent in an environment of 6°C, add the colorant to make the stock solution B, and refrigerate for storage until use.

[0050] (3) Add stock solution A and stock solution B into a constant temperature stirring kettle and stir and mix at 22°C.

[0051] (4) adding recombinant collagen, dissolving and stirring evenly, and finally adding sodium chloride, dissolving and stirring evenly to prepare the mucosal lifting agent.

[0052] Preparation Example 2

[0053] This preparation example provides a method for preparing a mucosal lifting agent for submucosal layer separation surgery, comprising the following steps: adding a gelling agent, recombinant collagen, poloxamer, a colorant, and sodium chloride into water, and stirring and mixing at 22°C.

[0054] Example 1

[0055] In this example, the method provided in Preparation Example 1 was used to prepare a mucosal lifting agent for submucosal layer separation. The mucosal lifting agent contained 1% sodium hyaluronate, 0.3% type I recombinant collagen, 0.3% type III recombinant collagen, 20% poloxamer 407, 0.05% colorant and 1% sodium chloride, with the balance being water.

[0056] Example 2

[0057] In this example, the method provided in Preparation Example 1 was used to prepare a mucosal lifting agent for submucosal layer separation. The mucosal lifting agent contained 0.1% sodium hyaluronate, 0.5% type I recombinant collagen, 0.1% type III recombinant collagen, 25% poloxamer 407, 0.01% colorant and 2% sodium chloride, with the balance being water.

[0058] Example 3

[0059] In this example, the method provided in Preparation Example 1 was used to prepare a mucosal lifting agent for submucosal layer separation. The mucosal lifting agent contained 2% sodium hyaluronate, 0.1% type I recombinant collagen, 0.5% type III recombinant collagen, 15% poloxamer 407, 0.1% colorant and 0.5% sodium chloride, with the balance being water.

[0060] Example 4

[0061] This embodiment provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that sodium hyaluronate is replaced with an equal amount of sodium alginate.

[0062] Example 5

[0063] This example provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that type I recombinant collagen is replaced with an equal amount of type II recombinant collagen.

[0064] Example 6

[0065] This example provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that type III recombinant collagen is replaced with an equal amount of type II recombinant collagen.

[0066] Example 7

[0067] This embodiment provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that type I recombinant collagen is not added, and the proportion of type I recombinant collagen is proportionally distributed to sodium hyaluronate and type III recombinant collagen.

[0068] Example 8

[0069] This embodiment provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that type III recombinant collagen is not added, and the proportion of type III recombinant collagen is proportionally distributed to sodium hyaluronate and type I recombinant collagen.

[0070] Example 9

[0071] This embodiment provides a mucosal lifting agent for submucosal layer separation, which differs from Example 1 only in that the mass percentage of Poloxamer 407 is 12%.

[0072] Example 10

[0073] This embodiment provides a mucosal lifting agent for submucosal layer separation, which differs from Example 1 only in that the mass percentage of Poloxamer 407 is 28%.

[0074] Example 11

[0075] This example provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that it is prepared using the method provided in Preparation Example 2.

[0076] Comparative Example 1

[0077] This comparative example provides a mucosal lifting agent for submucosal layer separation surgery, which differs from Example 1 only in that type I recombinant collagen and type III recombinant collagen are not added, and the proportions thereof are allocated to sodium hyaluronate.

[0078] Comparative Example 2

[0079] This comparative example provides a mucosal lifting agent for submucosal layer separation, which differs from Example 1 only in that poloxamer 407 is not added, and the remaining substances in the mucosal lifting agent are distributed in proportion.

[0080] Test Example 1

[0081] In this test, the mucosal elevating agent solutions prepared in the Examples and Comparative Examples were heated in a thermostatic heater at a temperature of 30-40°C, with each 1°C temperature node defined as a specific temperature. The solution was heated for 5 minutes at each temperature node and then removed from the heater to observe whether gelation occurred. When the gel completely stopped flowing, that temperature node was recorded as the phase transition temperature for the formulation. If the phase transition temperature was less than 30°C, it was recorded as <30°C. If no phase transition occurred at 40°C, it was recorded as >40°C. The test results are shown in Table 1.

[0082] Test Example 2

[0083] In this test example, the mucosal uplifting agent solution obtained by the embodiment and the comparative example is loaded into a disposable syringe, and a pig stomach is used as a test sample. First, the pig stomach is soaked in a physiological saline with a pH of 7 at 37°C and kept at a constant temperature for 10 minutes to allow the pig stomach sample to be evenly heated to human body temperature. Insert the syringe needle into the submucosal layer of the pig stomach, push in about 1 mL of the uplifting agent, and make the mucosa uplift, and continue to soak in a constant temperature physiological saline at 37°C for 3 minutes to fully gel. Then use dissecting scissors to cut off the mucosa of the uplifted part along the edge of the uplift, rinse the wound surface of the peeled mucosa with 37°C physiological saline for 30 minutes, and observe whether the hydrogel layer falls off in a large area. If it falls off in a large area, it is recorded as poor adhesion, a small amount of shedding is recorded as medium adhesion, and only almost no shedding is recorded as strong adhesion. The test results are shown in Table 1.

[0084] Table 1

[0085] Group Phase transition temperature (℃) Adhesion Example 1 About 35℃ powerful Example 2 About 33℃ powerful Example 3 About 34℃ powerful Example 4 About 30℃ powerful Example 5 About 33℃ powerful Example 6 About 33℃ powerful Example 7 About 31℃ powerful Example 8 About 31℃ powerful Example 9 Greater than 40℃ weak Example 10 Less than 30℃ powerful Example 11 About 33℃ middle Comparative Example 1 About 31℃ middle Comparative Example 2 Greater than 40℃ weak

[0086] As can be seen from Table 1:

[0087] (1) Comparing Example 1 with Examples 4-8 and Comparative Example 1, it can be seen that the present invention synergistically improves the adhesion ability of the gel by compounding sodium hyaluronate, type I recombinant collagen, and type III recombinant collagen. The adhesion ability of the gel without adding recombinant collagen is significantly reduced.

[0088] In addition, the ratio of sodium hyaluronate, type I recombinant collagen, and type III recombinant collagen also affects the phase transition temperature of the gel, maintaining the phase transition temperature within the body temperature range, which is suitable for the application environment of mucosal lifting agents in submucosal layer separation surgery;

[0089] (2) Comparing Example 1 with Examples 9-10 and Comparative Example 2, it can be seen that the present invention adjusts the phase transition temperature of the mucosal lifting agent by adding poloxamer and further adjusting its addition amount. Too much or too little addition will affect its phase transition temperature. The amount of poloxamer also affects the adhesion ability of the gel.

[0090] (3) Comparing Example 1 with Example 11, it can be seen that the preparation method provided by the present invention can effectively improve the dissolution efficiency and solution uniformity of the product. The product of Example 11 showed local agglomeration during the preparation process, and the uniformity of the product after complete gelation was poor and the adhesion ability was weak.

[0091] Test Example 3

[0092] This test example tests the gel protection effect of the mucosal lifting agent solutions provided in Example 1 and Example 4 under different pH digestive tract environments. The sample preparation and testing methods are carried out with reference to Test Example 2, and artificial gastric juice with pH = 2, physiological saline with pH = 7, and PBS solution with pH = 7.4 are prepared respectively. The wound surface is rinsed with the prepared solution to observe whether the hydrogel layer has fallen off over a large area. The test results show that the protective effect under a pH of 2 environment is about 3-48h (the protective effect of Example 1 is about 3-6h, and the protective effect of Example 4 can reach 24-48h), the protective effect under a pH of 7 environment is about 24-48h, and the protective effect under a pH of 7.4 environment is about 12-24h.

[0093] In summary, the present invention provides a mucosal lifting agent for submucosal layer separation surgery, which is a liquid with low viscosity at room temperature, is conducive to injection, and has a temperature-sensitive phase change effect. After being injected into the submucosal membrane of the patient's affected area, the liquid injection is quickly transformed into a gel state under the influence of temperature, reducing fluidity, thereby facilitating the accumulation of the lifting agent, increasing the height of the mucosal lifting, and creating a safer operating space for gastrointestinal mucosal dissection surgery.

[0094] The applicant declares that the above is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the scope of protection and disclosure of the present invention.

Claims

1. A mucosal lifting agent for submucosal layer separation, characterized in that: The mucosal lifting agent contains a gelling agent, recombinant collagen and poloxamer.

2. The mucosal lifting agent according to claim 1, characterized in that The gelling agent includes any one of sodium hyaluronate, sodium polyglutamate, polylysine hydrochloride or sodium alginate, or a combination of at least two thereof; Preferably, the molecular weight of the gelling agent is 200 to 1800 kDa; Preferably, the recombinant collagen includes any one of type I recombinant collagen, type II recombinant collagen or type III recombinant collagen, or a combination of at least two thereof; Preferably, the poloxamer comprises poloxamer 407 and / or poloxamer 188.

3. The mucosal lifting agent according to claim 1 or 2, characterized in that Calculated by mass percentage, the mucosal lifting agent contains 0.1% to 2% of gelling agent, 0.1% to 1% of recombinant collagen and 15% to 25% of poloxamer.

4. The mucosal lifting agent according to any one of claims 1 to 3, characterized in that The mucosal lifting agent contains sodium hyaluronate, type I recombinant collagen, type III recombinant collagen and poloxamer 407; Preferably, the mucosal lifting agent contains, by weight percentage, 0.1% to 2% sodium hyaluronate, 0.1% to 0.5% type I recombinant collagen, 0.1% to 0.5% type III recombinant collagen and 15% to 25% poloxamer 407.

5. The mucosal lifting agent according to any one of claims 1 to 4, characterized in that The mucosal elevating agent also contains a colorant; Preferably, the colorant comprises methylene blue and / or sodium indigo disulfonate; Preferably, the content of the colorant in the mucosal lifting agent is 0.01% to 0.1% by mass.

6. The mucosal lifting agent according to any one of claims 1 to 5, characterized in that Calculated by mass percentage, the mucosal lifting agent contains 0.1% to 2% sodium hyaluronate, 0.1% to 0.5% type I recombinant collagen, 0.1% to 0.5% type III recombinant collagen, 15% to 25% poloxamer 407, 0.01% to 0.1% colorant and 0.5% to 2% sodium chloride, with the balance being water.

7. A method for preparing the mucosal lifting agent according to any one of claims 1 to 6, characterized in that: The preparation method comprises the following steps: (1) stirring and mixing the gelling agent solution and the poloxamer solution; (2) adding recombinant collagen, dissolving and stirring to obtain the mucosal lifting agent; Preferably, the gelling agent solution in step (1) further contains a colorant; Preferably, step (2) further comprises adding sodium chloride, dissolving it and stirring to mix it; Preferably, the stirring temperature is 18-25°C.

8. A method for forming a gel of the mucosal lifting agent according to any one of claims 1 to 6, characterized in that: The gelling method comprises: placing the mucosal elevating agent in an environment of 30-40°C.

9. A thermosensitive hydrogel, characterized in that The thermosensitive hydrogel is prepared by the following steps: injecting the mucosal lifting agent according to any one of claims 1 to 6 into the submucosal layer of the digestive tract to form a hydrogel in situ at body temperature; Preferably, the digestive tract includes any one of the esophagus, stomach or intestine, or a combination of at least two of them.

10. Use of the mucosal lifting agent according to any one of claims 1 to 6 or the thermosensitive hydrogel according to claim 9 in the preparation of a preparation for assisting endoscopic mucosal dissection or endoscopic mucosal resection.