A tissue sealing system for digestive tract anastomosis protection and ESD wound isolation and a method of using the same
Patent Information
- Application Number
- CN202611078835.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-07-20
- Publication Date
- 2026-09-25
AI Technical Summary
[0023]1 .一种适用于内镜黏膜下剥离术术后创面隔离保护的的高粘附水凝胶能完全贴合各种复杂的创口形态，如不规则形状、大小不一，甚至多发性的微小创口，能实现理想的全方位隔离术后伤口。
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Figure CN122805865A_ABST
Abstract
Description
Technical Field
[0001] Endoscopic submucosal dissection (ESD) has become the standard minimally invasive technique for treating superficial gastrointestinal tumors. Its advantages include complete resection of the lesion in a single procedure, accurate pathological staging, and preservation of organ function. However, the artificial ulcers formed after ESD can lead to various adverse events, with delayed bleeding being one of the most common complications, occurring in 4.1%-8.5% of gastric ESD cases. Esophageal ESD also carries significant risks such as stricture, delayed bleeding, and perforation. Currently, clinical management of the wound after ESD mainly includes hemostatic clipping and double-layer suturing techniques. However, existing closure techniques have limitations, including complex operation, long processing time, limited effectiveness in closing large wounds, and leakage may still occur after clipping.
[0002] Anastomotic leakage (AL) is one of the most common and serious complications following gastrointestinal surgery. The incidence of AL after radical esophagectomy can reach 11%, with a related mortality rate of approximately 13%; in the esophageal cancer patient population, this incidence ranges from 4.94% to 23.17%, with a mortality rate as high as 5% to 41.6%. The incidence of AL after gastrectomy is 2.1% to 14.6%, with a mortality rate as high as 50%. In colorectal surgery, the incidence of AL is 5% to 12.3%, with a rate as high as 17.4%. AL can not only lead to fatal pelvic infections and sepsis, but also often results in the failure of sphincter-preserving surgery, ultimately requiring patients to undergo permanent colostomy.
[0003] Against this backdrop, there is a clear clinical need and sufficient scientific basis for a tissue sealing system for the protection of digestive tract anastomoses and the isolation of ESD wounds. Summary of the Invention
[0004] The purpose of this invention is to provide a tissue sealing system for gastrointestinal anastomosis protection and ESD wound isolation, and a method for preparing the same. This hydrogel possesses excellent adhesion, mechanical strength, and biocompatibility, making it suitable for gastrointestinal anastomosis protection and ESD wound isolation.
[0005] To achieve the above objectives, the present invention adopts the following technical solution.
[0006] A highly adhesive, tensile-resistant in-situ molding hydrogel suitable for lung parenchyma resection wounds, comprising a first component, a second component, a first component buffer, and a second component buffer. The first component is dissolved in a first component buffer to form a first solution; the second component is dissolved in a second component buffer to form a second solution. The first and second solutions react to form a hydrogel. The first component is either 8-arm-PEG-SG or DA-8-arm-PEG-SG; the second component is either trilysine, polyethyleneimine, or 8-arm-PEG-NH2 (HCl) or a combination thereof; the first component buffer is either phosphate buffer or water; and the second component buffer is either borate buffer or water.
[0007] Furthermore, the molecular weight of 8-arm-PEG-SG is between 4-20 kDa, and the molecular weight of DA-8-arm-PEG-SG is between 4-20 kDa.
[0008] Furthermore, the molecular weight of 8-arm-PEG-NH2(HCl) is between 4 and 20 kDa.
[0009] Furthermore, the molecular weight of trilysine is between 1 and 5 kDa.
[0010] Furthermore, the molecular weight of polyethyleneimine is between 1 and 5 kDa.
[0011] Furthermore, the mass-to-volume ratio between the first component and the first component buffer is 1:1.
[0012] Furthermore, when the first component buffer is phosphate buffer, the concentration of the phosphate buffer is 10-40 mmol / L.
[0013] Furthermore, the mass-to-volume ratio of the second component to the second component buffer is 1:1.
[0014] Furthermore, when the second component buffer is a borate buffer, the concentration of the borate buffer is 35-85 mmol / L.
[0015] It should be noted that the preparation method of DA-8-arm-PEG-SG here is as follows: 1 M 8-arm-PEG-SG and 1 M dopamine (DA) hydrochloride are pre-dissolved and mixed in a sample tube. Grafting reaction is carried out through the spontaneous reaction of the amino group of DA with 8-arm-PEG-SG. After an appropriate reaction time, the mixture is dried to obtain the DA-8-arm-PEG-SG polymer.
[0016] A method for using a highly adhesive hydrogel suitable for lung parenchymal resection wounds includes the following steps: S1, Dissolve the first component uniformly in the first component buffer solution; S2, Dissolve the second component uniformly in the second component buffer solution; S3 involves spraying the first and second components alternately and evenly onto the tissue in a 1:1 ratio to form a sheet-like hydrated and sealing hydrogel, thereby preventing lung leakage.
[0017] A tissue sealing system for protecting gastrointestinal anastomoses and isolating ESD wounds includes a first component, a second component, a first component buffer, and a second component buffer. The first component is dissolved in a first component buffer solution to form a first component solution; the second component is dissolved in a second component buffer solution to form a second component solution. The first and second component solutions react to form a hydrogel. The first component is one of 8-arm-PEG-SG, 4-arm-PEG-SG, and 4-arm-PEG-SS; the second component is one or a mixture of trilysine, polyethyleneimine, 8-arm-PEG-NH2 (HCl), and ε-polylysine; the buffer for the first component is phosphate buffer or water; and the buffer for the second component is borate buffer or water.
[0018] Furthermore, the molecular weights of 8-arm-PEG-SG, 4-arm-PEG-SG, and 4-arm-PEG-SS are between 4-20 kDa.
[0019] Furthermore, the molecular weight of 8-arm-PEG-NH2(HCl) is between 4 and 20 kDa.
[0020] Furthermore, the molecular weight of trilysine is between 1 and 5 kDa; the molecular weight of polyethyleneimine is between 1 and 5 kDa; and the molecular weight of ε-polylysine is between 1 and 5 kDa.
[0021] A method for preparing a tissue sealing system for gastrointestinal anastomosis protection and ESD wound isolation, characterized by comprising the following steps: S1, Dissolve the first component uniformly in the first component buffer solution to obtain the first component solution; S2, the second component is uniformly dissolved in the second component buffer solution to obtain the second component solution; S3, the first component solution and the second component solution are mixed in a 1:1 ratio, and a hydrogel is formed by the reaction to obtain the tissue sealing system.
[0022] Compared with the prior art, the beneficial effects of the present invention are as follows.
[0023] 1. A highly adhesive hydrogel suitable for wound isolation and protection after endoscopic submucosal dissection can completely conform to various complex wound morphologies, such as irregular shapes, different sizes, and even multiple micro-wounds, and can achieve ideal all-round isolation of postoperative wounds.
[0024] 2. The hydrogels are made of degradable materials during preparation, which ensures that they degrade in vivo and reduces clinical risks. Attached Figure Description
[0025] Figure 1 Image showing hydrogel sprayed onto the intestines.
[0026] Figure 2 This is a scanning electron microscope image of the hydrogel.
[0027] Figure 3 HE-stained sections were implanted into hydrogel muscle 4 weeks later. Detailed Implementation
[0028] First, the ratio and concentration of different components were adjusted to obtain the preparation effect of hydrogels in different embodiments, and their performance was studied.
[0029] Example 1: Weigh 1 gram of 8-arm-PEG-SG (molecular weight 20 kDa) and dissolve it in 1 ml of sterile water to prepare a first component solution; weigh 0.3 gram of trilysine (molecular weight 0.4 kDa) and dissolve it in 1 ml of sterile water to prepare a second component solution. Mix the liquid containing the first component and the liquid containing the second component in equal proportions; Example 2: Weigh 1 gram of 4-arm-PEG-SG (molecular weight 20 kDa) and dissolve it in 1 ml of sterile water to prepare a first component solution; weigh 0.1 gram of trilysine (molecular weight 0.4 kDa) and dissolve it in 1 ml of sterile water to prepare a second component solution. Mix the liquid containing the first component and the liquid containing the second component in equal proportions; Example 3: Weigh 1 gram of 4-arm-PEG-SS (molecular weight 20 kDa) and dissolve it in 1 ml of phosphate buffer (10 mmol / L) to prepare the first component solution; weigh 1.3 gram of 8-arm-PEG-NH2(HCl) (molecular weight 20 kDa) and dissolve it in 1 ml of sterile water to prepare the second component solution. Mix the solutions containing the first component and the second component in equal proportions; Example 4: Weigh 1 gram of 8-arm-PEG-SG (molecular weight 20 kDa) and dissolve it in 1 ml of phosphate buffer (10 mmol / L) to prepare the first component solution; weigh 0.3 gram of trilysine (molecular weight 0.4 kDa) and dissolve it in 1 ml of borate buffer (35 mmol / L) to prepare the second component solution. Mix the solutions containing the first and second components in equal proportions; Example 5: Weigh 1 gram of 4-arm-PEG-SG (molecular weight 20 kDa) and dissolve it in 1 ml of phosphate buffer (40 mmol / L) to prepare the first component solution; weigh 0.3 gram of ε-polylysine (molecular weight 0.4 kDa) and dissolve it in 1 ml of borate buffer (75 mmol / L) to prepare the second component solution. Mix the solutions containing the first and second components in equal proportions; Example 6: Weigh 1 gram of 4-arm-PEG-SS (molecular weight 20 kDa) and dissolve it in 1 ml of sterile water to prepare the first component solution; weigh 1.3 gram of 8-arm-PEG-NH2(HCl) (molecular weight 20 kDa) and dissolve it in 1 ml of borate buffer (85 mmol / L) to prepare the second component solution. Mix the solutions containing the first component and the second component in equal proportions; The present invention will now be described in detail with reference to the accompanying drawings and embodiments. Performance analysis of the above embodiments 1. Hydrogel degradation cycle test Take 0.5g of hydrogel, dry the sample to constant weight under room temperature and vacuum conditions before degradation, then immerse it in the degradation solution, and record the quality test of the process using an electronic balance at fixed times (2, 4, 8, 12, 16 weeks).
[0030] 2. Hydrogel swelling performance test Swelling studies were performed in phosphate-buffered saline (PBS) buffer (pH 7.4). After gelation, the initial height of the hydrogel was measured and defined as H. a The hydrogel was then immersed in PBS for 24 hours. After removing excess water from the surface, the sample was removed and its height was measured, which was defined as H. b The swelling ratio is calculated using Formula 1: (1) 3. Hydrogel fracture strength test A hole approximately 0.16 cm (+0.02 cm) in diameter was punched in a fresh pig casing. The gel product of this invention was applied to this hole to form a hydrogel of a specified thickness. Pressure was applied from below the casing using a phosphate buffer solution with a pH of 7.4 until the gel ruptured. The maximum pressure reading was recorded using a digital reader connected to a sensor. The rupture strength results are shown in Table 1. The data shows that the rupture strength of this sealing gel far exceeds the physiological pressure of holding one's breath or coughing, indicating that it possesses excellent mechanical properties and can be applied to the lungs.
[0031] 4. Hydrogel impermeability test Take a fresh pigskin and make a hole with a diameter of about 0.16 cm (+0.02 cm). Apply the gel product of this invention to the hole, add sterile water under the pigskin and apply pressure until the gel breaks. Record the maximum pressure.
[0032] 5. Gel formation time test Mix the liquid containing the first component and the liquid containing the second component in equal proportions and spray them into a small bottle. Pour the bottle over and observe its flow. Record the hydrogel formation time.
[0033] The experimental data are shown in Table 1. Table 1. Mechanical Strength Data of Hydrogels
[0034] For cell and animal experiments, the precursor solution is sterilized by filtration through a 0.2 μm filter.
[0035] Hydrogel morphology analysis and animal experimental characterization data are illustrated in Example 4. Weigh 1 part of 8-arm-PEG-SG (molecular weight 20 kDa) and dissolve it in 1 ml of phosphate buffer to prepare the first component solution; weigh 0.3 parts of trilysine (molecular weight 0.4 kDa) and dissolve it in 1 ml of borate buffer to prepare the second component solution. Mix the solutions containing the first and second components in equal proportions; 6. Hydrogel morphology analysis After the hydrogel formed by spraying is dehydrated with alcohol (30%-100%), it is then photographed with a scanning electron microscope.
[0036] 7. Rabbit muscle implantation experiment New Zealand rabbits were used for experimental purposes. Each rabbit was implanted with 3-4 test samples. After implantation, the condition of the implantation site, the general condition of the animals, and their behavior were closely observed. Four weeks after implantation, the rabbits were euthanized, and changes in normal tissue structures at all implantation sites were examined. Muscle tissue blocks were excised, fixed in formalin, and after tissue fixation, the implants were removed. The tissue was dehydrated with ethanol, cleared with xylene, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE).
Claims
1. A tissue sealing system for protecting digestive tract anastomoses and isolating ESD wounds, characterized in that: Includes a first component, a second component, a first component buffer, and a second component buffer; The first component is dissolved in a first component buffer solution to form a first component solution; the second component is dissolved in a second component buffer solution to form a second component solution. The first and second component solutions react to form a hydrogel. The first component is one of 8-arm-PEG-SG, 4-arm-PEG-SG, and 4-arm-PEG-SS; the second component is one or a mixture of trilysine, polyethyleneimine, 8-arm-PEG-NH2 (HCl), and ε-polylysine; the buffer for the first component is phosphate buffer or water; and the buffer for the second component is borate buffer or water.
2. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: The molecular weights of 8-arm-PEG-SG, 4-arm-PEG-SG, and 4-arm-PEG-SS are between 4-20 kDa.
3. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: The molecular weight of 8-arm-PEG-NH2(HCl) is between 4 and 20 kDa.
4. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: The molecular weight of trilysine is between 1 and 5 kDa; the molecular weight of polyethyleneimine is between 1 and 5 kDa; the molecular weight of ε-polylysine is between 1 and 5 kDa.
5. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: The mass-to-volume ratio of the first component to the first component buffer is 1:
1.
6. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: When the first component buffer is phosphate buffer, the concentration of phosphate buffer is 10-40 mmol / L.
7. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: The mass-to-volume ratio of the second component to the second component buffer is 1:
1.
8. The digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to claim 1, characterized in that: When the second component buffer is a borate buffer, the concentration of the borate buffer is 35-85 mmol / L.
9. A method for preparing a digestive tract anastomosis protection and ESD wound isolation tissue sealing system according to any one of claims 1-8, characterized in that: Includes the following steps: S1, Dissolve the first component uniformly in the first component buffer solution to obtain the first component solution; S2, the second component is uniformly dissolved in the second component buffer solution to obtain the second component solution; S3, the first component solution and the second component solution are mixed in a 1:1 ratio, and a hydrogel is formed by the reaction to obtain the tissue sealing system.