Rare-earth-based growth factor ReO-Ac, hydrocolloid dressing and preparation method of rare-earth-based growth factor ReO-Ac
By using the rare earth-based growth factor ReO@Ac in wound healing dressings, the problem of difficult to effectively utilize rare earth elements and eliminate free radicals in the prior art is solved, and efficient wound healing and tissue repair are achieved.
Patent Information
- Application Number
- CN202411604380.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-12
- Publication Date
- 2025-02-18
AI Technical Summary
The prior art is difficult to effectively utilize the antibacterial, anti-inflammatory and cell proliferation and differentiation properties of rare earth elements during wound healing, and lacks dressings that can eliminate free radicals for a long time.
Rare earth-based growth factor ReO@Ac is prepared by reacting rare earth nitrate compounds with acetic acid-sodium acetate buffer at a temperature of 100°C-150°C and fixed in a hydrocolloid dressing to form antioxidant and radical scavenging properties dressing.
The dressing has good biocompatibility and moisturizing properties, and can eliminate free radicals for a long time, promote wound healing, improve tissue repair speed, and reduce potential allergic reactions to the skin.
Smart Images
Figure CN119454752A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of liquid dressings, and in particular relates to a rare earth-based growth factor ReO@Ac and a hydrocolloid dressing and a preparation method thereof. Background Art
[0002] In daily life, skin tissue damage or defects caused by various external factors and chronic diseases can lead to wounds of varying sizes. Timely and effective trauma treatment cannot be ignored to avoid severe ulcers or even life-threatening consequences due to external bacterial infection. Over time, many changes have occurred in the methods of wound treatment. As a common material for wound treatment, medical dressings can help control bleeding, prevent infection, absorb secretions, and accelerate wound healing after loading various functional substances. With the development of medicine, the theory of moist wound healing has been proposed and widely studied and recognized. The main purpose of these dressings is to create a moist, sterile environment on the wound surface, which can enhance the activity of macrophages and fibroblasts, thereby increasing epithelial regeneration and relieving pain and itching caused by dryness during the healing process.
[0003] Rare earth elements are a group of metal elements with special chemical and physical properties. Their application in medicine is mainly due to their antibacterial, anti-inflammatory and cell proliferation and differentiation promoting abilities. Rare earth elements can interact with biomacromolecules such as proteins, affecting cell signal transduction pathways and thus regulating cell behavior. In wound management, these properties of rare earth elements can be used to reduce the risk of infection and promote wound healing.
[0004] A large number of rare earth element toxicology studies have shown that rare earth hydrates can change, modify and enhance the biological activity of rare earths to a great extent. They are substances with lower toxicity, and are less toxic than most organic synthetic compounds or transition metal hydrates. Rare earth metal elements are widely used in the medical field in anti-thrombotic drugs, burn drugs, anti-inflammatory and bactericidal drugs, anti-atherosclerosis, radionuclides and anti-tumor drugs, as well as analgesics and hypoglycemic drugs, but there are no reports on their use in the field of medical dressings. Rare earth-based growth factor hydrocolloid dressings are based on the expansion and optimization of the functions of existing dressings. This dressing can enable rare earth functional materials to continue to play a role at the wound site by fixing rare earth nanoparticles on the dressing material, thereby providing a microenvironment that is more conducive to wound healing.
[0005] In summary, rare earth elements have high chemical activity and coordination properties, and can be used to synthesize rare earth complexes with antibacterial properties. These complexes can interact with bacteria, destroy their cell walls, cell membranes, and intracellular DNA, proteins, and enzymes, thereby inhibiting the growth and reproduction of bacteria. In addition, rare earth elements doped into antibacterial materials can also produce synergistic antibacterial effects with other antibacterial agents, reducing the dosage of other antibacterial agents and obtaining composite antibacterial materials with stronger antibacterial ability.
[0006] Rare earth growth factor functional materials can clean and repair inflammatory factors at the wound healing surface of the human body, destroy most of the peptide bonds and hydrogen bonds in the peptidoglycan of inflammatory factors, cause the disintegration of the cross-linked network structure, and achieve the purpose of cleaning inflammatory factors. Summary of the invention
[0007] In view of this, the present invention aims to overcome the defects in the prior art and proposes a rare earth-based growth factor and a hydrocolloid dressing and a preparation method thereof. The hydrocolloid dressing of the present invention has good biocompatibility and moisturizing properties, thereby contributing to wound healing to achieve better trauma treatment effects.
[0008] To achieve the above object, the technical solution of the present invention is achieved as follows:
[0009] In a first aspect, the present invention provides a rare earth-based growth factor ReO@Ac, which is prepared by reacting a reaction solution including a rare earth nitrate compound solution and a buffer solution as raw materials at a temperature of 100°C-150°C, wherein the buffer solution includes acetic acid, sodium acetate and a solvent, and the mass ratio of sodium acetate to acetic acid is (0.5-2):1.
[0010] Preferably, the concentration of the rare earth nitrate compound in the reaction solution is 0.1-0.2 mol / L.
[0011] Preferably, the mass concentration of the buffer solution is 25%-50%.
[0012] Preferably, the rare earth nitrate compound is one or more of lanthanum nitrate hexahydrate, cerium nitrate hexahydrate, gadolinium nitrate hexahydrate, and yttrium nitrate hexahydrate.
[0013] Preferably, the solvent is deionized water or an organic solvent. Further, the organic solvent is one or more of dimethyl sulfoxide, dimethylformamide, and acetone.
[0014] In a second aspect, the present invention also provides a method for preparing the rare earth-based growth factor ReO@Ac, comprising the following steps:
[0015] The rare earth nitrate compound is dissolved in a solvent and mixed with a buffer solution, and reacted at a temperature of 100°C-150°C for 12-18 hours. After the reaction is completed, the excess unreacted impurities are removed by centrifugation to obtain the rare earth-based growth factor ReO@Ac.
[0016] In a third aspect, the present invention provides a hydrocolloid dressing prepared using the above-mentioned rare earth-based growth factor.
[0017] In a fourth aspect, the present invention provides a method for preparing the above-mentioned hydrocolloid dressing, which specifically comprises the following steps:
[0018] (1) Adding a polyisobutylene raw material to a kneader at 120-160° C. and stirring for 30-60 minutes, then lowering the temperature to room temperature, adding a polycationic compound, a polyanionic compound and a neutral polymer and stirring for 30-60 minutes, wherein the mass fraction of the polyisobutylene is 30%, the mass fraction of the polycationic compound is 15%, the mass fraction of the polyanionic compound is 20%, and the mass fraction of the neutral polymer is 35%.
[0019] (2) adding 1% to 2% by weight of the rare earth growth factor in the total raw materials of step (1) and stirring until dissolved, taking out the material after the stirring is completed, and cooling it naturally to form a gel block;
[0020] (3) Cut the rubber block and sandwich it between release papers, vulcanize it at 100-120° C. for 30-120 seconds, and cut it into the required size to obtain the final hydrocolloid dressing product.
[0021] Compared with the prior art, the present invention has the following advantages:
[0022] (1) The present invention uses rare earth compounds as precursors and uses acetic acid-sodium acetate buffer solution to regulate the pH of the reaction environment, which can affect the surface charge and solubility of cerium oxide particles, thereby further controlling the particle size and morphology of the particles, and controlling the growth rate and final particle size of the cerium oxide particles. In addition, the -COOH group is introduced into the rare earth growth factor system through reaction to modify the rare earth oxide. The introduced -COOH group will change the hydrophilicity and solubility of the rare earth oxide, thereby improving the biocompatibility of the material.
[0023] (2) The reaction solution of the present invention is subjected to high-speed centrifugation to remove impurities, and then subjected to high-temperature calcination to form a rich lamellar structure. The synthesized rare earth growth factor dressing has antioxidant and free radical scavenging properties and can effectively promote wound healing.
[0024] (3) The present invention synthesizes a rare earth growth factor capable of improving tissue repair ability by introducing rare earth elements. The factor has the characteristics of self-regeneration, optimization of absorption environment and simulation of enzyme activity, and can continuously remove various free radicals that are not conducive to wound healing. When removing free radicals, only the valence state of rare earth ions is converted, and no change in crystal structure occurs. Therefore, free radicals can be removed in a long-term and lasting manner, providing a favorable environment for the wound to absorb nutrients, improving the absorption efficiency of nutrients in the tissue repair process, and improving the overall speed of human tissue repair.
[0025] (4) The hydrocolloid dressing containing rare earth-based growth factors prepared by the present invention can provide a suitable moist environment for the wound, which helps to promote the formation of granulation tissue. Compared with traditional dressings, the new dressing will not leave sticky gel on the wound surface when removed, which makes it easier to observe changes in the wound and reduces potential allergic reactions to the skin. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 This is the infrared characterization test image of CO@Ac. DETAILED DESCRIPTION
[0027] Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the experimental methods, unless otherwise specified, are all conventional methods.
[0028] The present invention will be described in detail below with reference to the embodiments.
[0029] Example 1 Preparation and Synthesis of Rare Earth-Based Growth Factor CO@Ac
[0030] Weigh 168 g of cerium nitrate hexahydrate and dissolve it in 1.0 L of deionized water. Stir thoroughly to completely dissolve the cerium nitrate hexahydrate. Then weigh 300 g of CH3COONa and 300 g of CH3COOH and add 1.1 L of deionized water. Stir evenly in a three-necked flask to obtain an acetic acid-sodium acetate buffer solution. Slowly add the acetic acid-sodium acetate buffer solution to the cerium nitrate solution and heat under reflux in an oil bath at 100°C for 12 h.
[0031] After the reaction is completed, the reaction solution is allowed to stand for 6 hours, the upper clarified liquid is directly poured out, and the bottom suspension is centrifuged. The centrifuge is used for high-speed centrifugation at 10000rpm / 10min to remove excess unreacted impurities, and then the precipitate after centrifugation is immediately collected to obtain the rare earth-based growth factor CO@Ac.
[0032] Example 2 Preparation and Synthesis of Rare Earth-Based Growth Factor LO@Ac
[0033] Weigh 90.9 g of lanthanum nitrate hexahydrate and dissolve it in 1.0 L of deionized water. Stir thoroughly to completely dissolve the lanthanum nitrate hexahydrate. Then weigh 550 g of CH3COONa and 550 g of CH3COOH and add 1.1 L of deionized water to obtain an acetic acid-sodium acetate buffer solution. Slowly add it to the cerium nitrate solution and heat under reflux in an oil bath at 100°C for 12 h.
[0034] After the reaction is completed, the reaction solution is allowed to stand for 10 hours, the upper clarified liquid is directly poured out, and the bottom suspension is centrifuged. The centrifuge is used for high-speed centrifugation at 10000rpm / 10min to remove excess unreacted impurities, and then the precipitate after centrifugation is immediately collected to obtain the rare earth-based growth factor LO@Ac.
[0035] Example 3 Preparation and Synthesis of Rare Earth-Based Growth Factor YO@Ac
[0036] Weigh 168 g of yttrium nitrate hexahydrate and dissolve it in 1.0 L of deionized water. Stir thoroughly to completely dissolve the yttrium nitrate hexahydrate. Then weigh 183.3 g of CH3COONa and 183.3 g of CH3COOH and add 1.1 L of deionized water to obtain an acetic acid-sodium acetate buffer solution. Slowly add it to the cerium nitrate solution and heat under reflux in an oil bath at 100°C for 12 h.
[0037] After the reaction is completed, the reaction solution is allowed to stand for 10 hours, the upper clarified liquid is directly poured out, and the bottom suspension is centrifuged. The centrifuge is used for high-speed centrifugation at 10000rpm / 10min to remove excess unreacted impurities, and then the precipitate after centrifugation is immediately collected to obtain the rare earth-based growth factor YO@Ac.
[0038] Comparative Example 1
[0039] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the buffer solution only includes 300 g of CH3COONa, and the prepared material is the rare earth-based growth factor CO@Ac-1.
[0040] Comparative Example 2
[0041] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the buffer solution only includes 300 g of CH3COOH, and the prepared material is the rare earth-based growth factor CO@Ac-2.
[0042] Comparative Example 3
[0043] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the mass of cerium nitrate hexahydrate is 46 g, and the prepared material is the rare earth-based growth factor CO@Ac-3.
[0044] Comparative Example 4
[0045] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the mass of cerium nitrate hexahydrate is 273 g, and the prepared material is the rare earth-based growth factor CO@Ac-4.
[0046] Comparative Example 5
[0047] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the buffer solution includes 80 g of CH3COONa and 300 g of CH3COOH, and the prepared material is the rare earth-based growth factor CO@Ac-5.
[0048] Comparative Example 6
[0049] The preparation method of the rare earth-based growth factor in this comparative example is basically the same as that in Example 1, except that the buffer solution includes 610 g of CH3COONa and 300 g of CH3COOH, and the prepared material is the rare earth-based growth factor CO@Ac-6.
[0050] Test Example 1 Salicylic Acid Colorimetric Method for Testing the Active Oxygen Scavenging Capacity of Rare Earth-Based Growth Factors
[0051] 16 mg of sodium salicylate was weighed and added to 10 mL of deionized water, mixed evenly for later use; 50 mg of ferrous sulfate heptahydrate was weighed and added to 9 mL of deionized water, mixed evenly for later use; then 1 mL of 1.5% H2O2 was added to the ferrous sulfate heptahydrate solution and reacted for 10 min to obtain active oxygen; the rare earth-based growth factor material prepared in Examples 1-3 and Comparative Examples 1-6 was added to the reaction system at 1% to react with the active oxygen; and the absorbance at 510 nm was tested by an ultraviolet spectrophotometer at 0 min, 60 min and 120 min after the rare earth growth factor material was mixed with the active oxygen; since salicylic acid reacts with active oxygen to generate a colored product, the absorbance value can reflect the content of active oxygen in the system; therefore, the active oxygen scavenging ability of the material can be evaluated according to the change in absorbance.
[0052] The test results of the UV spectrophotometer at 0min, 60min and 120min after the rare earth-based growth factor material was mixed with the active oxygen are shown in Table 1. As can be seen from the table, the absorbance at 510nm of the blank group without any rare earth material added increased significantly with the extension of time, proving that the content of active oxygen in the environment is gradually increasing. Compared with the blank group, the absorbance at 510nm of the three groups of samples with the addition of rare earth-based growth factor materials decreased to varying degrees, and tended to decrease with the extension of time. The best effect was the CO@Ac material, which could effectively remove all active oxygen in the environment after mixing with active oxygen, and could inhibit the generation of active oxygen in the environment for a long time.
[0053] Table.1 Absorbance at OD510nm after materials were exposed to active oxygen for different time
[0054] Grouping 0min 60min 120min Blank Group 0.602 0.707 0.813 CO@Ac 0.026 0.023 0.009 LO@Ac 0.303 0.212 0.079 YO@Ac 0.397 0.203 0.107 CO@Ac-1 0.561 0.525 0.474 CO@Ac-2 0.527 0.504 0.503 CO@Ac-3 0.528 0.529 0.519 CO@Ac-4 0.605 0.533 0.468 CO@Ac-5 0.627 0.531 0.492 CO@Ac-6 0.570 0.574 0.502
[0055] Test Example 2 IR Characterization of CO@Ac
[0056] pass Figure 1 It can be seen from the IR curve of CO@Ac material that 1410cm -1 The CO stretching vibration absorption peak in the carboxyl group is 1544 cm -1 The CC in-plane bending vibration absorption peak is 1720cm -1 The C=O stretching vibration absorption peak in the carboxyl group is 2930 cm -1 The antisymmetric stretching vibration absorption peak of methyl CH is 3380cm -1 The absorption peak at the antisymmetric stretching vibration of methyl CH proves that the -COOH group in acetic acid has been introduced into the CO@Ac system through the reaction. The cerium oxide is modified by the method of the present invention, and the introduced -COOH group will change the hydrophilicity and solubility of the cerium oxide and improve the biocompatibility of the material.
[0057] Application Example Preparation of Hydrocolloid Dressing
[0058] First, add the hydrocolloid raw material polyisobutylene when the kneader temperature is stable at 150°C, adjust the speed to 300rpm and stir for 30 minutes, then lower the temperature to room temperature, add the remaining additives and stir for 30 minutes. The additives include polycationic compounds, polyanionic compounds and neutral polymer components mixed together. The mass fraction of polyisobutylene is 30%, the mass fraction of polycationic compounds is 15%, the mass fraction of polyanionic compounds is 20%, and the mass fraction of neutral polymers is 35%. Then slowly add 1% of rare earth-based growth factor CO@Ac and stir until the rare earth particles basically disappear. During this period, a shovel is used to peel off the particles stuck to the outer wall and the shaft. After stirring, take out the material and cool it naturally to form a rubber block. Finally, cut the rubber block into small rubber blocks of about 9g, sandwich them between release papers, vulcanize them at 110°C for 30 seconds, and cut them into the required size to obtain the final rare earth-based growth factor hydrocolloid dressing product.
[0059] The present invention prepares a rare earth-based growth factor ReO@Ac, which can continuously remove various free radicals that are not conducive to wound healing. When removing free radicals, only the valence state of rare earth ions is converted, and no change in the crystal structure occurs. Therefore, free radicals can be removed in a long-lasting manner, providing a favorable environment for the wound to absorb nutrients. Adding it to a hydrocolloid dressing can improve the absorption efficiency of nutrients in the tissue repair process and improve the overall speed of human tissue repair.
[0060] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims
1. A rare earth-based growth factor ReO@Ac, characterized in that: The method is prepared by reacting a reaction solution including a rare earth nitrate compound solution and a buffer solution as raw materials at a temperature of 100°C-150°C, wherein the buffer solution includes acetic acid, sodium acetate and a solvent, and the mass ratio of the sodium acetate to the acetic acid is (0.5-2):
1.
2. The rare earth-based growth factor ReO@Ac according to claim 1, characterized in that: The concentration of the rare earth nitrate compound in the reaction solution is 0.1-0.2 mol / L.
3. The rare earth-based growth factor ReO@Ac according to claim 1, characterized in that: The mass concentration of the buffer solution is 25%-50%.
4. The rare earth-based growth factor ReO@Ac according to claim 1, characterized in that: The rare earth nitrate compound is one or more of lanthanum nitrate hexahydrate, cerium nitrate hexahydrate, gadolinium nitrate hexahydrate, and yttrium nitrate hexahydrate.
5. The rare earth-based growth factor ReO@Ac according to claim 1, characterized in that: The solvent is deionized water or an organic solvent.
6. The rare earth-based growth factor ReO@Ac according to claim 5, characterized in that: The organic solvent is one or more of dimethyl sulfoxide, N,N-dimethylformamide and acetone.
7. The method for preparing the rare earth-based growth factor ReO@Ac according to any one of claims 1 to 6, characterized in that: The steps include: The rare earth nitrate compound is dissolved in a solvent and mixed with a buffer solution, and reacted at a temperature of 100°C-150°C for 12-18 hours. After the reaction is completed, the excess unreacted impurities are removed by centrifugation to obtain the rare earth-based growth factor ReO@Ac.
8. A hydrocolloid dressing prepared using the rare earth-based growth factor ReO@Ac as described in any one of claims 1 to 6.
9. The method for preparing the hydrocolloid dressing according to claim 8, characterized in that: The specific steps include: (1) adding a polyisobutylene raw material to a kneader at 120-160° C. and stirring for 30-60 minutes, then lowering the temperature to room temperature, adding a polycationic compound, a polyanionic compound and a neutral polymer and stirring for 30-60 minutes, wherein the mass fraction of the polyisobutylene is 30%, the mass fraction of the polycationic compound is 15%, the mass fraction of the polyanionic compound is 20%, and the mass fraction of the neutral polymer is 35%; (2) adding 1% to 2% by weight of the rare earth growth factor ReO@Ac in the total raw materials of step (1) and stirring until dissolved, taking out the material after the stirring is completed, and cooling it naturally to form a gel block; (3) Cut the rubber block and sandwich it between release papers, vulcanize it at 100-120° C. for 30-120 seconds, and cut it into the required size to obtain the final hydrocolloid dressing product.