Gel for covering digestive tract wounds and preparation method thereof

Abstract

The invention discloses gel for digestive tract wound covering and a preparation method thereof, and belongs to the technical field of gel materials, the gel comprises the following components by weight: 0.01%-0.5% of cationic polysaccharide, 0.5%-20% of a film forming component, and 79.5%-99.5% of an auxiliary material. The gel can be used as a physical barrier to be adhered to the surface of a digestive tract when aiming at a wound surface generated in an endoscopic surgery, so that the flushing of digestive juice in the digestive tract to the wound surface is effectively prevented, the adhesion is avoided, the long-term slow release of the cationic polysaccharide is maintained, the wound healing is promoted, and the bleeding is quickly stopped.

Description

Technical Field

[0001] This invention relates to the field of gel materials technology, and in particular to gels for covering gastrointestinal wounds and methods for preparing them. Background Technology

[0002] Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become routine minimally invasive treatments for early-stage gastrointestinal tumors and large polyps. Although they avoid the major trauma of traditional open surgery, they still create wounds on the inner wall of the digestive tract. Timely and good healing of these wounds is crucial for preventing postoperative complications and promoting rapid patient recovery.

[0003] Current clinical wound management methods often include conservative drug treatment and metal clip closure: Conservative drug treatment mainly uses high-dose proton pump inhibitors combined with gastric mucosal protectants. Although it can relieve gastric acid erosion, it is a systemic medication and cannot provide local physical protection for the wound. The wound is still exposed to food residue, digestive juice flushing, and friction from gastrointestinal peristalsis, which can easily lead to adverse consequences such as delayed healing and bleeding. Metal clip closure is only suitable for small perforations or clear bleeding points. It is difficult to completely close large, irregularly shaped, wrinkled, or corner-shaped superficial wounds, and the clipping operation may cause secondary tissue damage.

[0004] Compared to the two methods mentioned above, gel-based materials have natural advantages for wound treatment. They can form a physical barrier at the wound site, achieving localized targeted protection, adapting to wounds of different sizes and shapes, eliminating the need for mechanical clamping, and avoiding the risk of secondary injury. However, existing gels (such as cyanoacrylate tissue adhesives) are mostly limited to adhesion and hemostasis, lacking the ability to actively promote tissue regeneration and repair. Therefore, there is a need in this field to develop a novel digestive tract wound covering material that achieves both effective isolation and protection of the wound and active promotion of repair, meeting the urgent clinical need for rapid and safe healing of digestive tract wounds. Summary of the Invention

[0005] The present invention aims to overcome the shortcomings of existing technologies where gels cannot promote rapid healing of digestive tract wounds, and provides a gel for covering digestive tract wounds and its preparation method.

[0006] To achieve the above objectives, the technical solution of the present invention is: to provide a gel for covering digestive tract wounds, comprising the following components by weight percentage, Cationic polysaccharides: 0.01%~0.5%; Film-forming component: 0.5%~20%; Auxiliary materials: 79.5%~99.5%.

[0007] In one embodiment, the cationic polysaccharide conforms to one or more of the following formulas (I) to (IV). (I) (II) (III) (IV) Formula (I) is a polycationic polysaccharide composed of polysaccharide molecules with (1→6) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (II) is a polycationic polysaccharide composed of polysaccharide molecules with (1→4) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (III) is a polycationic polysaccharide composed of polysaccharide molecules with (1→3) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (IV) is a polycationic polysaccharide composed of polysaccharide molecules with (1→2) glycosidic bonds as the main chain grafted with polyamine compounds. R6 is selected from hydrogen atoms or (V); R7 is selected from protected or unprotected amino groups; R8 is selected from either a hydrogen atom or R6.

[0008] In one embodiment, the molecular weight of the cationic polysaccharide is 40-120 kDa.

[0009] In one embodiment, the film-forming component includes one or more of polyvinyl alcohol, poloxamer series polymers, cellulose, ethyl cellulose, or hydroxypropyl methylcellulose.

[0010] In one embodiment, the excipient comprises the following components by weight percentage: Moisturizer 0.5%~10%; Chelating agent 0.05%~0.5%; Phosphate 0.01%~0.5%; Water for injection: 68.5%–99%.

[0011] In one embodiment, the humectant includes one or more of glycerol or propylene glycol.

[0012] In one embodiment, the chelating agent comprises disodium ethylenediaminetetraacetate.

[0013] In one embodiment, the phosphate includes one or more of sodium monohydrogen phosphate or sodium dihydrogen phosphate.

[0014] In one embodiment, the pH value of the gel is 7.0-7.4.

[0015] This invention also provides a method for preparing a gel for covering digestive tract wounds, comprising the following steps: Step S1: Mix the film-forming components, moisturizer, chelating agent, phosphate and water for injection evenly and completely dissolve to form material A; Step S2: Add the cationic polysaccharide to material A, stir evenly to obtain material B; Step S3: Fill material B into a bottle, seal and package it, and then sterilize it by irradiation to obtain a gel for covering digestive tract wounds.

[0016] In summary, this invention provides a gel for covering digestive tract wounds and a method for preparing the same. The gel comprises cationic polysaccharides, film-forming components, chelating agents, phosphates, and humectants. For wounds generated during laparoscopic surgery, the gel can act as a physical barrier to adhere to the surface of the digestive tract, effectively preventing digestive juices from scouring the wound, avoiding adhesions, and maintaining the long-term slow release of cationic polysaccharides, thus promoting wound healing and rapid hemostasis.

[0017] To make the above-mentioned features and advantages of the invention more apparent and understandable, specific embodiments are described below, and detailed descriptions are provided in conjunction with the accompanying drawings. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the gel preparation process for covering digestive tract wounds in this invention.

[0019] Figure 2 This is a comparative graph showing the results of the gel used for covering digestive tract wounds in this invention in promoting wound healing time.

[0020] Figure 3 The image shows the results of the gel used in this invention for covering gastrointestinal wounds reducing postoperative bleeding after intestinal surgery. Detailed Implementation

[0021] To make the objectives and technical solutions of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0022] To address the current lack of effective wound dressings for promoting surgical wound healing in laparoscopic surgery, this invention provides a gel for covering gastrointestinal wounds, the gel comprising the following components by weight percentage: Cationic polysaccharides: 0.01%~0.5%; Film-forming components: 0.5%~20%; Auxiliary materials: 79.5%~99.5%.

[0023] The cationic polysaccharide has a molecular weight of 40-120 kDa. It is a positively charged polycationic polysaccharide obtained by reacting a polysaccharide with a polyamine compound. The cationic polysaccharide conforms to one or more of the following formulas (I) to (IV). (I) (II) (III) (IV) Formula (I) is a polycationic polysaccharide composed of polysaccharide molecules with (1→6) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (II) is a polycationic polysaccharide composed of polysaccharide molecules with (1→4) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (III) is a polycationic polysaccharide composed of polysaccharide molecules with (1→3) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (IV) is a polycationic polysaccharide composed of polysaccharide molecules with (1→2) glycosidic bonds as the main chain grafted with polyamine compounds. R6 is selected from hydrogen atoms or (V); R7 is selected from protected or unprotected amino groups; R8 is selected from either a hydrogen atom or R6.

[0024] The film-forming component includes one or more of polyvinyl alcohol, poloxamer series polymers, cellulose, ethyl cellulose, or hydroxypropyl methyl cellulose.

[0025] The excipients comprise the following components by weight percentage: Moisturizer: 0.5%~10%; Chelating agent: 0.05%~0.5%; Phosphate: 0.01%~0.5%; Water for injection: 68.5%~99%; The humectant includes one or more of glycerol or propylene glycol; The chelating agent includes disodium ethylenediaminetetraacetate; The phosphate includes one or more of sodium monohydrogen phosphate or sodium dihydrogen phosphate.

[0026] The pH value of the gel is 7.0-7.4.

[0027] This invention uses water for injection as a sterile dispersion medium to achieve uniform dispersion and dissolution of all components. A humectant maintains the moisture content and water-holding capacity of the gel system, ensuring the continuity and integrity of the gel barrier. A chelating agent, by complexing trace metal ions within the system and the digestive tract environment, inhibits the destructive effect of metal ions on the gel, enhances the physicochemical stability of the gel in the dynamic digestive tract environment, reduces the potential irritation of the wound site by free metal ions, and lowers the risk of inflammatory reactions. Phosphate, as a physiological pH buffer component, regulates and maintains the pH value of the gel system. Simultaneously, the film-forming agent selected in this invention possesses excellent film-forming properties, biocompatibility, and delivery capability to endoscopic instruments, helping to construct a continuous, moist, and dynamic physical barrier on the surface of the digestive tract wound. This effectively blocks the erosion of digestive juices, the mechanical stimulation of food residues, and the friction of digestive tract peristalsis, providing a stable local microenvironment for wound healing.

[0028] In addition, cationic polysaccharides are introduced into the gel system as a repair-promoting active component to promote the healing process of gastrointestinal mucosal epithelial wounds and make up for the limitation of existing gel materials that only provide single isolation.

[0029] This invention also provides a method for preparing a gel for covering gastrointestinal wounds, such as... Figure 1 As shown, the specific steps are as follows: Step S1: Mix the film-forming components, moisturizer, chelating agent, phosphate and water for injection evenly and completely dissolve to form material A; Step S2: Add the cationic polysaccharide to material A, stir evenly to obtain material B; Step S3: Fill material B into a bottle, seal and package it, and then sterilize it by irradiation to obtain a gel for covering digestive tract wounds.

[0030] The following detailed description, in conjunction with specific embodiments, provides a further explanation of the gel for covering digestive tract wounds of the present invention and its preparation method.

[0031] Example 1 This embodiment uses the following steps to prepare a gel for covering gastrointestinal wounds: Step S1: Mix 0.5% to 20% of the film-forming component, 0.1% to 1% of the humectant, 0.01% to 0.5% of the chelating agent, 0.01% to 0.5% of the phosphate, and 68.5% to 99% of the water for injection evenly until all components are completely dissolved to form material A. (2) Add 0.01% to 0.5% cationic polysaccharide by mass to material A, stir evenly to obtain material B; (3) Pour material B into a bottle, seal and package it, and then sterilize it by irradiation to obtain a gel for covering digestive tract wounds.

[0032] Example 2 Verify the therapeutic effect of the gel of the present invention for covering gastrointestinal wounds on a rat endoscopic biopsy wound model. Establishing a rat endoscopic biopsy wound model Adult female SD rats were selected, weighed and recorded, and randomly divided into groups of 10 rats each. Before the experiment, the rats were fasted for 12 hours (with free access to water) and anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3 mL / 100g).

[0033] Prepare the endoscope system. Disinfect the lens with gauze soaked in 70% alcohol and lubricate the colonoscope with paraffin oil. Connect the air syringe filled with air to the instrument channel of the colonoscope. During insertion, the air should not be injected too quickly or too much. It is appropriate to inject 1 mL of air each time, with a total volume of 2-3 mL. Observe the degree of abdominal distension of the rat during air injection.

[0034] Anesthetized rats were placed in a supine position and fixed on a clean operating table. A disposable 3 mL pipette was used to repeatedly flush the intestines with saline solution through the anus to remove feces. After exposing the rat's anus, a colonoscope was inserted through the anus. With the intestinal wall visualized, the endoscope was advanced along the lumen, gently sliding and reaching the splenic flexure at the terminal colon, where the intestinal mucosa was clearly visible. Biopsy forceps were inserted through the operating channel. Under direct vision, the open jaws of the biopsy forceps were aligned with the target mucosal area, and the angle between the forceps and the intestinal wall was adjusted to approximately 90 degrees to ensure that the mucosa and part of the submucosal tissue could be harvested. Active bleeding from the wound surface should be visible, indicating successful model establishment.

[0035] Drug administration To investigate the effect of the gel used for covering digestive tract wounds in this invention on colonic wounds in rats, rats were grouped as follows: Blank control group: 400 μL of normal saline was applied to the wound area before drug administration; Blank matrix group: 400 μL of the dressing prepared by the film-forming components and excipients of this invention was applied to the wound area during drug administration; The technical group of this invention: When administering the medication, apply 400 μL of the gel provided by this invention for covering gastrointestinal wounds to the wound area; After treatment, the rats were placed in a warm, bright, and comfortable environment to await their recovery. Colonoscopy was performed every two days to observe the healing of the colonic wound. The time to complete wound healing was recorded, and the mean healing time and standard deviation (SD) were calculated. Statistical results are as follows: Figure 2 In a rat model treated with the gel for covering digestive tract wounds according to the present invention, the wound healing process was significantly accelerated, and the healing period was the shortest among the test groups. These results indicate that the gel for covering digestive tract wounds provided by the present invention can effectively promote the repair process of digestive tract wounds.

[0036] Example 3 Verify the intervention effect of the gel of the present invention for covering gastrointestinal wounds on postoperative bleeding in intestinal wounds. The surgical experiment was performed according to the protocol described in Example 2. 24 hours after the operation, fecal occult blood in rat feces was measured using a fecal occult blood qualitative detection kit (o-toluidine method).

[0037] Simultaneously collect and test fecal samples. Use a toothpick to pick up a small amount of feces (10-50 mg) and smear it onto a white porcelain plate. Add 0.1 mL of colorimetric solution A to evenly cover the smeared sample; add 0.1 mL of colorimetric solution B to the area where solution A was added, immediately start timing and observe the color change; interpret the results within 2 minutes. If a blue color appears within 2 minutes, it indicates the presence of hemoglobin (Hb) in the feces or a positive fecal occult blood test, and score according to Table 1.

[0038] Table 1 Color Changes and Interpretation Criteria in Fecal Occult Blood Detection The scores were statistically analyzed, and the results are as follows: Figure 3 The results showed that the gel used for covering digestive tract wounds in this invention can promote rapid hemostasis of wounds after laparoscopic surgery.

[0039] In summary, this invention provides a gel for covering digestive tract wounds and a method for preparing the same. The gel comprises cationic polysaccharides, film-forming components, chelating agents, phosphates, and humectants. For wounds generated during laparoscopic surgery, the gel can act as a physical barrier to adhere to the surface of the digestive tract, effectively preventing digestive juices from scouring the wound, avoiding adhesions, and maintaining the long-term slow release of cationic polysaccharides, thus promoting wound healing and rapid hemostasis.

[0040] Although the present invention has been disclosed above by way of embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make some modifications and refinements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A gel for covering wounds in the digestive tract, characterized in that, Includes the following components by weight percentage, Cationic polysaccharides: 0.01%~0.5%; Film-forming component: 0.5%~20%; Auxiliary materials: 79.5%~99.5%.

2. The gel for covering digestive tract wounds as described in claim 1, characterized in that, The cationic polysaccharide conforms to one or more of the following formulas (I) to (IV): （Ⅰ） （Ⅱ） （Ⅲ） （Ⅳ） Formula (I) is a polycationic polysaccharide composed of polysaccharide molecules with (1→6) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (II) is a polycationic polysaccharide composed of polysaccharide molecules with (1→4) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (III) is a polycationic polysaccharide composed of polysaccharide molecules with (1→3) glycosidic bonds as the main chain grafted with polyamine compounds; Formula (IV) is a polycationic polysaccharide composed of polysaccharide molecules with (1→2) glycosidic bonds as the main chain grafted with polyamine compounds. R6 is selected from hydrogen atoms or (V); R7 is selected from protected or unprotected amino groups; R8 is selected from either a hydrogen atom or R6.

3. The gel for covering digestive tract wounds as described in claim 2, characterized in that, The molecular weight of the cationic polysaccharide is 40-120 kDa.

4. The gel for covering digestive tract wounds as described in claim 3, characterized in that, The film-forming component includes one or more of polyvinyl alcohol, poloxamer series polymers, cellulose, ethyl cellulose, or hydroxypropyl methyl cellulose.

5. The gel for covering digestive tract wounds as described in claim 3, characterized in that, The excipients comprise the following components by weight percentage: Moisturizer 0.5%~10%; Chelating agent 0.05%~0.5%; Phosphate 0.01%~0.5%; Water for injection: 68.5%–99%.

6. The gel for covering digestive tract wounds as described in claim 4, characterized in that, The humectant includes one or more of glycerol or propylene glycol.

7. The gel for covering digestive tract wounds as described in claim 4, characterized in that, The chelating agent includes disodium ethylenediaminetetraacetate.

8. The gel for covering digestive tract wounds as described in claim 4, characterized in that, The phosphate includes one or more of sodium monohydrogen phosphate or sodium dihydrogen phosphate.

9. The gel for covering digestive tract wounds as described in claim 4, characterized in that, The pH value of the gel is 7.0-7.

4.

10. A method for preparing a gel for covering gastrointestinal wounds, comprising the preparation of the gel described in any one of claims 1-9, characterized in that, Includes the following steps, Step S1: Mix the film-forming components, moisturizer, chelating agent, phosphate and water for injection evenly and completely dissolve to form material A; Step S2: Add the cationic polysaccharide to material A, stir evenly to obtain material B; Step S3: Fill material B into a bottle, seal and package it, and then sterilize it by irradiation to obtain a gel for covering digestive tract wounds.

Images