Medical gel dressing for wound repair and preparation process thereof
By improving the konjac glucomannan gel dressing with cross-linking agents and antibacterial structures, the problems of insufficient moisture absorption and antibacterial properties were solved, achieving a highly efficient wound repair effect.
Patent Information
- Application Number
- CN202511278927.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-09
- Publication Date
- 2025-11-14
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Existing konjac glucomannan gel dressings are insufficient in terms of moisture absorption and antibacterial properties to meet the requirements for use on large-area wounds, and traditional dry dressings tend to stick to the wound, prolonging healing time and increasing the risk of scarring.
Using aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate as substrates, a highly cross-linked gel is formed through a cross-linking agent. This combines the antibacterial structure of oleanolic acid with the quaternary ammonium cation of sodium hyaluronate to enhance the gel's liquid absorption and antibacterial properties.
It improves the stability and absorbency of gel dressings, enhances antibacterial properties, shortens wound healing time, prevents infection, and promotes wound repair.
Smart Images
Figure SMS_1
Abstract
Description
Technical Field
[0001] This invention relates to the field of materials technology, specifically to a medical gel dressing for wound repair and its preparation process. Background Technology
[0002] The skin, the largest organ in the human body, plays a crucial role in regulating body temperature and transmitting information about the external environment, such as pain and heat. Injury to the skin can cause varying degrees of harm. Skin injuries are inevitable in daily life, and wound healing is a lengthy and complex process. Therefore, functional wound dressings are needed to accelerate wound healing. Traditional dry dressings, such as gauze, tend to stick to the wound and cannot maintain a moist environment, leading to prolonged healing time and an increased risk of scar hyperplasia. Therefore, the development of intelligent dressings that combine moisturizing, antibacterial, and healing-promoting functions has become a clinical necessity.
[0003] Hydrogel dressings are biocompatible, easy to remove and replace, and simple to use, making them a research hotspot in recent years and gradually being widely used in clinical practice. Among many gel dressing matrices, biomass macromolecules such as konjac glucomannan have the effect of promoting coagulation and wound growth, and are therefore often used as medical dressing base materials. However, pure konjac glucomannan gel dressings do not have antibacterial properties, and their moisture absorption is difficult to meet the requirements for use on large-area wounds. Therefore, the development of konjac glucomannan-based hydrogel dressings with excellent comprehensive properties such as antibacterial properties is of great significance for their further application. Summary of the Invention
[0004] In order to solve the problems mentioned in the background art, the purpose of this invention is to provide a medical gel dressing for wound repair and its preparation process.
[0005] The objective of this invention can be achieved through the following technical solutions: A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: Aldehyde-based konjac glucomannan 40-50 parts; 10-15 parts of sodium aldehyde hyaluronic acid; Crosslinking agent 1.5-5 parts; 150-200 parts of deionized water.
[0006] As a further aspect of the present invention, the aldehyde-based konjac glucomannan is prepared by the following method: Add dextran to deionized water and stir until homogeneous. Then add sodium periodate to the resulting mixture. After the addition is complete, place the mixture in the dark and stir at room temperature for 12-24 hours. Then add diethylene glycol to quench the mixture and continue stirring for 1-2 hours. Dialyze the mixture for 2-3 days and then freeze-dry it to obtain aldehyde-based konjac glucomannan.
[0007] As a further aspect of the present invention, the aldehyde-based sodium hyaluronate is prepared by the following method: Step S1: Add sodium hyaluronate to an aqueous ethanol solution with a volume fraction of 50-60%. After the addition is complete, stir mechanically to mix evenly and place in an ice bath environment. Then add the functionalizing agent to the resulting mixed solution. After the addition is complete, remove from the ice bath and stir at a temperature of 30-40℃ for 3-6 hours. Then evaporate to remove the solvent and separate the product to obtain functionalized sodium hyaluronate. Step S2: Add functionalized sodium hyaluronate to an ethanol aqueous solution with a volume fraction of 60-70%, stir and mix until a uniform mixture is formed, then add 3-dimethylaminobenzaldehyde to the mixture. After the addition is complete, raise the temperature to 70-80℃ at a heating rate of 5-10℃ / min, keep it at this temperature for 6-12 hours, centrifuge the product, and purify it to obtain aldehyde-based sodium hyaluronate.
[0008] As a further aspect of the present invention, in step S1, the functionalizing agent is 2-bromobutyryl bromide or 4-bromobutyryl chloride.
[0009] In the above technical solution, firstly, a functionalizing agent is used to functionalize sodium hyaluronate to obtain sodium hyaluronate containing halogen substituents in its structure, namely functionalized sodium hyaluronate. Then, under high temperature conditions, the halogen substituents undergo a quaternization reaction with the tertiary amino group in the structure of 3-dimethylaminobenzaldehyde, thereby achieving the purpose of simultaneously introducing quaternary ammonium salt functional groups and aldehyde groups into the structure of sodium hyaluronate, and obtaining aldehyde-based sodium hyaluronate.
[0010] As a further aspect of the present invention, the crosslinking agent is prepared by the following method: Halogenated oleanolic acid derivatives and anhydrous ethanol are added to the polymerization reactor. After the addition is complete, nitrogen gas is introduced to purge the air, and stirring is started. After a homogeneous mixture is formed, the chain elongating agent is added to the mixture. After the addition is complete, heating is started, and the temperature is raised to 60-70℃. The mixture is kept at this temperature and stirred for 3-6 hours. Then, an acid-binding agent is added to the polymerization reactor. After the addition is complete, the mixture is kept at this temperature and stirred for 12-16 hours. The solvent is evaporated and removed, the material is cooled and discharged, and the product is collected. After purification, the crosslinking agent can be obtained.
[0011] As a further aspect of the present invention, the halo-oleanolic acid derivative is prepared by the following method: Oleanolic acid was added to acetone. After the addition was complete, stirring was started to form a homogeneous mixture. Then, the accelerator and condensing agent were added to the mixture. After the addition was complete, the mixture was stirred at room temperature for 1-2 hours. Then, bis(2-chloroethyl)amine hydrochloride was added, and the temperature was raised to 30-40°C and kept at this temperature for 4-6 hours. The solvent was then evaporated to remove the product, which was collected and purified to obtain the halogenated oleanolic acid derivative.
[0012] As a further embodiment of the present invention, the accelerator is N-hydroxysuccinimide or 4-dimethylaminopyridine; the condensing agent is dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.
[0013] The chain elongating agent is any one of 1,8-diamino-3,6-dioxaoctane, 1,11-diamino-3,6,9-trioxaundecane, or 3,6,9,12-tetraoxatetradecane-1,14-diamine.
[0014] In the above technical solution, the active carboxyl substituent in the oleanolic acid structure can undergo an amidation reaction with the secondary amine group in the bis(2-chloroethyl)amine hydrochloride structure under the action of an accelerator and a condensing agent, thereby obtaining a halooleanolic acid derivative containing two equivalent halogen substituents in its structure. Under the action of an acid-binding agent, the halogen substituent can undergo a continuous substitution reaction with the active amino group in the chain elongator structure to obtain a macromolecular crosslinking agent with an alternating linkage structure. By controlling the ratio of the halooleanolic acid derivative to the chain elongator, the end of the obtained crosslinking agent structure can be made to be an active amino group.
[0015] As a further aspect of the present invention, the molar ratio of the halo-oleanolic acid derivative and the chain elongating agent is 1:1.1-1.2.
[0016] A process for preparing a medical gel dressing for wound repair includes the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 50-60℃ and stir continuously for 30-60 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0017] In the above technical solution, through heating and mixing, the active amino groups at both ends of the crosslinking agent can undergo Schiff base crosslinking with the aldehyde functional groups in the structure of aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate, thereby making konjac glucomannan and sodium hyaluronate a highly crosslinked gel.
[0018] The beneficial effects of this invention are: This invention utilizes a cross-linking agent to interconnect the various raw materials in a gel dressing. On one hand, this highly cross-linked gel exhibits superior stability and mechanical properties, overcoming the instability issues associated with using konjac glucomannan alone as a gel dressing. Furthermore, the increased cross-linking degree further enhances the gel's porosity, positively impacting its absorbency. On the other hand, the cross-linking agent possesses an alternating linkage structure containing the natural antibacterial structure oleanolic acid. This structure can inactivate bacteria by disrupting their structure and interfering with key metabolic processes, thus exhibiting excellent antibacterial activity and endowing the gel dressing with superior antibacterial properties. The ether bonds within the cross-linking agent structure possess strong hydrophilicity, enhancing the gel dressing's absorbency and improving its ability to absorb wound exudate. In addition, this invention uses sodium hyaluronate, containing a quaternary ammonium cationic antibacterial agent, as the base material for the gel dressing. This synergistic effect with oleanolic acid significantly improves the antibacterial properties of the gel dressing, preventing bacterial erosion and wound infection, and mitigating the impact on wound healing speed.
[0019] This invention uses biomass konjac glucomannan and sodium hyaluronate as gel substrates, which have good biocompatibility and can adhere closely to the wound. It can not only effectively protect the wound, but also keep the wound moist, accelerate epithelial cell migration, shorten healing time, and promote rapid wound healing.
[0020] Of course, any product implementing this invention does not necessarily need to achieve all of the advantages described above at the same time. Detailed Implementation
[0021] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0022] Preparation Example 1 Preparation of aldehyde-based konjac glucomannan: 1.2g of dextran was added to deionized water and stirred until homogeneous. Then, 0.5g of sodium periodate was added to the resulting mixture. After the addition was complete, the mixture was placed in the dark and stirred at room temperature for 18 hours. Then, 2.5mL of diethylene glycol was added to quench the mixture, and stirring was continued for 1 hour. The mixture was then dialyzed for 3 days and then freeze-dried to obtain aldehyde-based konjac glucomannan.
[0023] Preparation Example 2 Preparation of sodium aldehyde hyaluronic acid: Step S1: Add 1.5g of sodium hyaluronate to a 60% (v / v) aqueous ethanol solution. After the addition is complete, stir mechanically to mix evenly and place in an ice bath environment. Then add 0.6g of 4-bromobutyryl chloride to the resulting mixed solution. After the addition is complete, remove from the ice bath and stir at 35°C for 4 hours. Then evaporate to remove the solvent and separate the product to obtain functionalized sodium hyaluronate. Step S2: Add 1g of functionalized sodium hyaluronate to a 70% (v / v) aqueous ethanol solution and stir until a homogeneous mixture is formed. Then add 0.3g of 3-dimethylaminobenzaldehyde to the mixture. After the addition is complete, raise the temperature to 80℃ at a rate of 10℃ / min and keep it at that temperature for 9 hours. Centrifuge the product and purify it to obtain aldehyde-based sodium hyaluronate.
[0024] Preparation Example 3 The crosslinking agent is prepared using the following method: Step A: Add 0.6g of oleanolic acid to acetone. After the addition is complete, start stirring to form a homogeneous mixture. Then add 0.1g of 4-dimethylaminopyridine and 0.3g of dicyclohexylcarbodiimide to the mixture. After the addition is complete, stir at room temperature for 1 hour. Then add 0.23g of bis(2-chloroethyl)amine hydrochloride and raise the temperature to 35°C. Keep it at this temperature for 6 hours. Evaporate to remove the solvent, collect the product, and purify it to obtain the halo-oleanolic acid derivative. Step B: Add 0.5g of halooleanolic acid derivative and anhydrous ethanol to the polymerization reactor. After the addition is complete, purge with nitrogen to purge air and start stirring. After a homogeneous mixture is formed, add 0.14g of 1,8-diamino-3,6-dioxaoctane to the mixture. After the addition is complete, start heating and keep stirring at 65°C for 4 hours. Then add 0.05g of triethylamine to the polymerization reactor. After the addition is complete, continue stirring at 65°C for 16 hours. Evaporate the solvent, cool down and discharge the product. Collect the product and purify it to obtain the crosslinking agent.
[0025] Example 1 A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: 40 parts of aldehyde-based konjac glucomannan; 10 parts of sodium aldehyde hyaluronic acid; 1.5 parts of crosslinking agent; 150 portions of deionized water.
[0026] The preparation process of medical gel dressings is characterized by comprising the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 60°C and stir continuously for 40 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0027] The preparation method of aldehyde-based konjac glucomannan is described in Preparation Example 1; the preparation method of aldehyde-based sodium hyaluronate is described in Preparation Example 2; the preparation method of crosslinking agent is described in Preparation Example 3, and the following are all the same.
[0028] Example 2 A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: 45 parts of aldehyde-based konjac glucomannan; 12 parts of sodium aldehyde hyaluronate; Crosslinking agent 4; 180 portions of deionized water.
[0029] The preparation process of medical gel dressings is characterized by comprising the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 60°C and stir continuously for 40 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0030] Example 3 A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: 50 parts of aldehyde-based konjac glucomannan; 15 parts of sodium aldehyde hyaluronic acid; 5 parts crosslinking agent; 200 portions of deionized water.
[0031] The preparation process of medical gel dressings is characterized by comprising the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 60°C and stir continuously for 40 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0032] Comparative Example 1 A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: 45 parts of aldehyde-based konjac glucomannan; 12 parts of sodium aldehyde hyaluronate; Ethylenediamine 4; 180 portions of deionized water.
[0033] The preparation process of medical gel dressings is characterized by comprising the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add ethylenediamine to the precursor solution. After the addition is complete, raise the temperature to 60°C and stir continuously for 40 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0034] Comparative Example 2 A medical gel dressing for wound repair, made from the following raw materials measured in parts by weight: 45 parts of aldehyde-based konjac glucomannan; 12 parts sodium hyaluronate; Crosslinking agent 4; 180 portions of deionized water.
[0035] The preparation process of medical gel dressings is characterized by comprising the following steps: Step 1: Add aldehyde-based konjac glucomannan and sodium hyaluronate to deionized water, and mix thoroughly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 60°C and stir continuously for 40 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.
[0036] Test case a. Moisture absorption performance test: Gel dressings with a mass of w were selected from the examples and comparative examples, and immersed in PBS at a controlled temperature of 37°C. After 1 hour, they were removed, gently blotted dry with filter paper, and then quickly weighed and recorded as mass W. The swelling rate of each gel dressing was calculated using the formula [(Ww) / w]×100% to evaluate the moisture absorption performance of the gel dressings. b. Antibacterial performance test: The antibacterial properties of each gel dressing were tested according to the antibacterial efficacy test method (General Chapter 1121) of the Pharmacopoeia of the People's Republic of China (2020 edition). Staphylococcus aureus was selected as the test bacteria, tryptic soy agar medium was selected as the culture medium, and the amount of gel dressing added was 10%. The antibacterial rate was calculated by the formula [(initial colony count - colony count after culture) / initial colony count] × 100%. The test results are shown in the table below: Table 1 - Test Results
[0037] Analysis and testing results show that the gel dressing prepared in this embodiment of the invention has good moisture absorption and antibacterial properties, which can meet the requirements for use in medical dressings.
[0038] Replacing the crosslinking agent with a conventional ethylenediamine crosslinking agent reduces the ether bond content in the gel molecular chain and eliminates the oleanolic acid antibacterial structure, resulting in a significant decrease in both the moisture absorption and antibacterial properties of the gel dressing. Replacing aldehyde-based sodium hyaluronate with conventional sodium hyaluronate, on the one hand, prevents the formation of a crosslinking structure, leading to a decrease in the porosity of the gel dressing and a substantial reduction in moisture absorption; on the other hand, the absence of quaternary ammonium cationic antibacterial groups also negatively impacts the antibacterial properties of the gel dressing.
[0039] This document uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of these embodiments are merely to aid in understanding the method and core ideas of the present invention, including the best mode, and to enable any person skilled in the art to practice the present invention, including manufacturing and using any device or system, and implementing any combined method. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the scope of protection of the claims. The scope of protection of this patent is defined by the claims and may include other embodiments that can be conceived by those skilled in the art. If these other embodiments have structural elements similar to those expressed in the claims, or if they include equivalent structural elements that are not substantially different from those expressed in the claims, then these other embodiments should also be included within the scope of the claims.
[0040] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A medical gel dressing for wound repair, characterized in that, It is made from the following raw materials, measured in parts by weight: Aldehyde-based konjac glucomannan 40-50 parts; 10-15 parts of sodium aldehyde hyaluronic acid; Crosslinking agent 1.5-5 parts; 150-200 parts of deionized water.
2. The medical gel dressing for wound repair according to claim 1, characterized in that, The aldehyde-based konjac glucomannan was prepared using the following method: Add dextran to deionized water and stir until homogeneous. Then add sodium periodate to the resulting mixture. After the addition is complete, place the mixture in the dark and stir at room temperature for 12-24 hours. Then add diethylene glycol to quench the mixture and continue stirring for 1-2 hours. Dialyze the mixture for 2-3 days and then freeze-dry it to obtain aldehyde-based konjac glucomannan.
3. The medical gel dressing for wound repair according to claim 1, characterized in that, The aldehyde-based sodium hyaluronate is prepared using the following method: Step S1: Add sodium hyaluronate to an aqueous ethanol solution with a volume fraction of 50-60%. After the addition is complete, stir mechanically to mix evenly and place in an ice bath environment. Then add the functionalizing agent to the resulting mixed solution. After the addition is complete, remove from the ice bath and stir at a temperature of 30-40℃ for 3-6 hours. Then evaporate to remove the solvent and separate the product to obtain functionalized sodium hyaluronate. Step S2: Add functionalized sodium hyaluronate to an ethanol aqueous solution with a volume fraction of 60-70%, stir and mix until a uniform mixture is formed, then add 3-dimethylaminobenzaldehyde to the mixture. After the addition is complete, raise the temperature to 70-80℃ at a heating rate of 5-10℃ / min, keep it at this temperature for 6-12 hours, centrifuge the product, and purify it to obtain aldehyde-based sodium hyaluronate.
4. The medical gel dressing for wound repair according to claim 3, characterized in that, In step S1, the functionalizing agent is 2-bromobutyryl bromide or 4-bromobutyryl chloride.
5. A medical gel dressing for wound repair according to claim 1, characterized in that, The crosslinking agent is prepared using the following method: Halogenated oleanolic acid derivatives and anhydrous ethanol are added to the polymerization reactor. After the addition is complete, nitrogen gas is introduced to purge the air, and stirring is started. After a homogeneous mixture is formed, the chain elongating agent is added to the mixture. After the addition is complete, heating is started, and the temperature is raised to 60-70℃. The mixture is kept at this temperature and stirred for 3-6 hours. Then, triethylamine is added to the polymerization reactor. After the addition is complete, the mixture is kept at this temperature and stirred for 12-16 hours. The solvent is evaporated to remove the product, the product is cooled and discharged, and the product is collected. After purification, the crosslinking agent can be obtained.
6. A medical gel dressing for wound repair according to claim 5, characterized in that, The halo-substituted oleanolic acid derivative was prepared by the following method: Oleanolic acid was added to acetone. After the addition was complete, stirring was started to form a homogeneous mixture. Then, the accelerator and condensing agent were added to the mixture. After the addition was complete, the mixture was stirred at room temperature for 1-2 hours. Then, bis(2-chloroethyl)amine hydrochloride was added, and the temperature was raised to 30-40°C and kept at this temperature for 4-6 hours. The solvent was then evaporated to remove the product, which was collected and purified to obtain the halogenated oleanolic acid derivative.
7. A medical gel dressing for wound repair according to claim 6, characterized in that, The accelerator is N-hydroxysuccinimide or 4-dimethylaminopyridine; the condensing agent is dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.
8. A medical gel dressing for wound repair according to claim 5, characterized in that, The chain elongating agent is any one of 1,8-diamino-3,6-dioxaoctane, 1,11-diamino-3,6,9-trioxaundecane, or 3,6,9,12-tetraoxatetradecane-1,14-diamine.
9. A medical gel dressing for wound repair according to claim 5, characterized in that, The molar ratio of the halogenated oleanolic acid derivative to the chain elongator is 1:1.1-1.
2.
10. A preparation process for a medical gel dressing for wound repair as described in claim 1, characterized in that, Includes the following steps: Step 1: Add aldehyde-based konjac glucomannan and aldehyde-based sodium hyaluronate to deionized water, and mix evenly by mechanical stirring to form a precursor solution; The second step is to add the crosslinking agent to the precursor solution. After the addition is complete, raise the temperature to 50-60℃ and stir continuously for 30-60 minutes. Then, stop heating and allow it to cool naturally to obtain the gel dressing.