Functional rare earth growth factor as well as preparation method and application thereof

Abstract

The invention provides a functional rare earth growth factor and a preparation method and application thereof, the rare earth growth factor comprises PEG-MoS2 and nano cerium oxide particles CeO2-NPs in a mass ratio of 1: (0.2-5), the PEG-MoS2 is a solid phase material with the surface modified with PEG, and the solid phase material is MoS2. The two materials of PEG-MoS2 and CeO2NPs are compounded, the rare earth growth factor obtained after compounding can effectively remove active oxygen existing in a wound, and the wound healing rate is effectively increased.

Description

Technical Field

[0001] The invention belongs to the field of medical materials, and in particular relates to a functional rare earth growth factor and a preparation method and application thereof. Background Art

[0002] With the development of modern medicine, wound management has evolved from simple covering protection to a complex treatment process involving multiple aspects such as promoting cell proliferation, reducing inflammation and accelerating tissue regeneration. In this context, wound dressings came into being. The skin wound healing process involves platelets, inflammatory cells, epithelial cells, keratinocytes, fibroblasts, multiple cytokines, growth factors and other bioactive molecules, as well as interactions with extracellular matrix (ECM) components mediated by integrin receptors and adhesion molecules. In acute wounds, the healing process is controlled by these growth factors, cytokines and chemokines, which induce the reconstruction of skin barrier function through the healing process. Usually, inflammatory cells infiltrate the wound site to produce a proteolytic environment, leading to a long-term upregulation of proinflammatory cytokines and chemokines, thereby inhibiting the normal progress of wound healing. This environment causes the degradation and sequestration of growth factors and cytokines at the wound site, inhibiting the healing of the wound surface.

[0003] Growth factors play a vital role in the process of wound healing. They can stimulate cell growth and differentiation, and accelerate various stages of wound healing, such as hemostasis, inflammation, proliferation, re-epithelialization and remodeling. However, traditional growth factor aqueous solutions are easily lost during use and have a short half-life. Rare earth growth factor dressing is an advanced medical dressing that combines rare earth elements and growth factors. It can not only maintain an ideal moist environment for the wound, but also promote cell proliferation and wound healing by releasing growth factors. The development of this dressing is based on the modern wound management concept, namely the moist healing theory, which believes that the speed and quality of wound healing can be significantly improved under appropriate temperature and humidity.

[0004] The unpaired electrons in the 4f electron layer of rare earth elements make them highly chemically active and coordinated. This property enables rare earth elements to interact with bacteria and destroy their cell walls, cell membranes, and intracellular DNA, proteins, and enzymes, thereby hindering the life activities of bacteria and inhibiting their growth and reproduction. Develop rare earth growth factor dressings with antibacterial effects. 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.

[0005] By combining the unique properties of rare earth elements with the biological activity of growth factors, rare earth growth factor dressings are developed, which are expected to bring revolutionary progress in the field of wound treatment. The antibacterial and anti-inflammatory effects of rare earth elements and their influence on cell signaling pathways, coupled with the ability of growth factors to regulate cell behavior, make this dressing have great potential in promoting wound healing, reducing inflammatory responses and improving tissue regeneration efficiency. Summary of the invention

[0006] In view of this, the present invention aims to overcome the defects in the prior art and proposes a functional rare earth growth factor and a preparation method and application thereof.

[0007] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0008] In the first aspect, the present invention provides a functional rare earth growth factor, which includes PEG-MoS2 and nano-cerium oxide particles CeO2-NPs in a mass ratio of 1: (0.2-5), wherein PEG-MoS2 is a solid phase material with polyethylene glycol (PEG) modified on the surface, and the solid phase material is MoS2.

[0009] Preferably, the preparation method of PEG-MoS2 comprises the following steps: using PEG as a surface modification material, modifying the surface of MoS2 with polyethylene glycol by a heterogeneous solid-liquid reaction under heating reflux conditions to finally obtain PEG-MoS2.

[0010] Preferably, the preparation method of PEG-MoS2 comprises the following steps:

[0011] Take a molybdenum source compound and thiourea, add polyethylene glycol and a solvent, then heat to 80-100°C, and continue heating, reflux and stirring for 12-24 hours under this condition. After the reaction is completed, dry and grind to obtain a powder material PEG-MoS2.

[0012] Preferably, the molybdenum source compound is one or a mixture of two or more of ammonium molybdate, molybdenum pentachloride, and molybdenum oxide;

[0013] Preferably, the mass ratio of the molybdenum source compound to thiourea is 1:(1-4).

[0014] Preferably, the volume ratio of the polyethylene glycol to the solvent is 1:(10-20).

[0015] Preferably, the solvent is deionized water.

[0016] Preferably, the preparation method of the nano cerium oxide particles CeO2-NPs comprises the following steps: adding a cerium source compound to a buffer solution to obtain a reaction solution, performing a hydrothermal reaction at 180-220°C after the reaction solution is completely dissolved, and after the reaction is completed, allowing the reaction solution to stand and centrifuge, collecting the precipitate after centrifugation, and obtaining nano cerium oxide particles CeO2-NPs.

[0017] Preferably, the concentration of the cerium source compound in the reaction solution is 0.05-0.1 mol / L.

[0018] Preferably, the cerium source compound is one or a mixture of two or more of ammonium cerium nitrate, cerium chloride heptahydrate, cerium chloride, and cerium carbonate.

[0019] Preferably, the buffer solution is an aqueous solution containing sodium acetate and acetic acid, and the amount of sodium acetate and acetic acid added to the buffer solution is 1-3g of acetic acid per 1g of sodium acetate, that is, the mass ratio of sodium acetate to acetic acid is 1:(1-3). One of the purposes of the aqueous solution of sodium acetate and acetic acid is to adjust the pH, and the particle size of the cerium oxide particles can be adjusted by adjusting the pH.

[0020] Preferably, the mass concentration of the buffer solution is 30%-50%.

[0021] In a second aspect, the present invention also provides a method for preparing the above-mentioned functional rare earth growth factor, comprising the following steps:

[0022] S1: Preparation of PEG-MoS2: Take a molybdenum source compound and thiourea, add polyethylene glycol and a solvent, then heat up, and continue heating and reflux stirring at 80-100°C for 12-24 hours. After the reaction is completed, dry and grind to obtain a powder material PEG-MoS2;

[0023] S2: Preparation of CeO2-NPs:

[0024] The cerium source compound is added to the buffer solution, and after the mixed solution is completely dissolved, a hydrothermal reaction is carried out at 180-220° C. After the reaction is completed, the reaction solution is allowed to stand and centrifuged, and the precipitate after centrifugation is collected to obtain nano-cerium oxide particles CeO2-NPs;

[0025] S3: Preparation of functional rare earth growth factors:

[0026] PEG-MoS2 and CeO2 NPs were mixed and ground, and functional rare earth growth factors were obtained after grinding.

[0027] In a third aspect, the present invention further provides a medical dressing, wherein the dressing contains the above-mentioned functional rare earth growth factor.

[0028] Preferably, the added amount of the functional rare earth growth factor is 0.5%-1.0%.

[0029] In a fourth aspect, the present invention further provides a method for preparing the above-mentioned medical dressing, which specifically comprises the following steps:

[0030] (1) dissolving the sodium carboxymethyl cellulose solution and the polyvinyl alcohol solution at a constant temperature, and the dissolved solution is determined as solution A;

[0031] (2) taking rubber and paraffin oil and adding 0.5% to 1.0% by weight of a functional rare earth growth factor material, and then stirring and dissolving, the resulting mixed solution is solution B;

[0032] (3) Pour solution B into solution A and stir continuously to fully mix the two. Adjust the total dosage of the mixed solution, add a mixture of sodium bicarbonate and citric acid, and heat and stir.

[0033] (4) After the solution of step (3) is cooled, it is applied to an anti-adhesive film and subjected to a freeze-thaw cycle to obtain a medical dressing.

[0034] Compared with the prior art, the present invention has the following advantages:

[0035] (1) The rare earth cerium element in the functional rare earth growth factor of the present invention has high biological activity. The nano rare earth cerium oxide prepared by the hydrothermal method has a smaller particle size distribution range, increases fat solubility and solubility, strengthens the penetration ability of cell membranes, and improves the bioavailability of drugs. In addition, the rare earth growth factor material 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, resulting in the disintegration of the cross-linked network structure, thereby achieving the purpose of cleaning inflammatory factors.

[0036] (2) The present invention compounds the two materials of synthesized PEG-MoS2 and CeO2-NPs. The rare earth growth factor obtained after compounding can effectively remove the active oxygen present in the wound and effectively improve the wound healing rate.

[0037] (3) The size of the rare earth growth factor material prepared by the present invention is controlled to be about 500-1400nm, which can enhance the proliferation and migration of keratinocytes and fibroblasts, and accelerate the migration and tube-forming ability of vascular endothelial cells. After the rare earth growth factor is made into a dressing, it has antioxidant and free radical scavenging properties, and can promote wound healing well. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is the particle size test result of the rare earth growth factor material of Example 1 of the present invention. DETAILED DESCRIPTION

[0039] 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.

[0040] The present invention will be described in detail below with reference to the embodiments.

[0041] Example 1

[0042] (1) Preparation of PEG-MoS2

[0043] Weigh 20g of ammonium molybdate and 36.5g of thiourea, add 400mL of deionized water and 20mL of PEG-400, then heat to 100°C, set a condenser above the three-necked flask, pass running cold water, and stir continuously at 100°C for 18h. After the reaction is completed, transfer the reaction solution to a crystallization dish, dry and concentrate it at 80°C to a solid, and grind it in a mortar to obtain the final powder material PEG-MoS2.

[0044] (2) Preparation of cerium oxide nanoparticles CeO2 NPs

[0045] Preparation of nano-cerium oxide material CeO2-NPs by hydrothermal hydrolysis of ammonium cerium nitrate: Weigh 2.74g of ammonium cerium nitrate and add it to a buffer solution composed of sodium acetate (15g), acetic acid (15g) and deionized water (70mL). After the mixed solution is completely dissolved, transfer it to a hydrothermal reactor. After the hydrothermal reactor is completely sealed, place the reactor in an electric blast oven, set the oven temperature to 220°C, and continue the reaction at this temperature for 12 hours. After the reaction is completed, let the reaction solution stand for 6-10 hours and then cool to room temperature. Open the hydrothermal reactor and centrifuge the reaction solution. The centrifuge is centrifuged at 10000rpm / 10min to remove excess unreacted impurities. Then, the precipitate after centrifugation is immediately collected to obtain cerium oxide nanoparticles CeO2-NPs.

[0046] (3) Compounding of rare earth growth factor CeO2-MoS2 (mass ratio is 1:2)

[0047] PEG-MoS2 and CeO2-NPs were weighed at a mass ratio of 1:2, and then the two powders were ground together using a mortar to obtain rare earth growth factor CeO2-MoS2 material.

[0048] Example 2

[0049] The preparation method of the rare earth growth factor of this embodiment is basically the same as that of Example 1, except that: in step (1), the molybdenum source compound is molybdenum pentachloride, the addition amount is 36.5 g, and the deionized water is 200 mL; in step (2), the cerium source compound is cerium chloride heptahydrate, the addition amount is 1.30 g, and the acetic acid is 30 g; in step (3), the mass ratio of PEG-MoS2 to CeO2-NPs is 1:1.

[0050] Example 3

[0051] The preparation method of the rare earth growth factor of this embodiment is basically the same as that of Example 1, except that: in step (1), the molybdenum source compound is molybdenum oxide, the addition amount is 10 g, and the addition amount of thiourea is 40 g; in step (2), the cerium source compound is cerium carbonate, the addition amount is 3.22 g, acetic acid is 30 g, and deionized water is 20 mL; in step (3), the mass ratio of PEG-MoS2 to CeO2-NPs is 1:3.

[0052] Example 4

[0053] The preparation method of the rare earth growth factor in this embodiment is basically the same as that in Example 1, except that the mass ratio of PEG-MoS2 to CeO2-NPs is 1:4.

[0054] Example 5

[0055] The preparation method of the rare earth growth factor in this embodiment is basically the same as that in Example 1, except that the mass ratio of PEG-MoS2 to CeO2-NPs is 1:5.

[0056] Example 6

[0057] The preparation method of the rare earth growth factor in this embodiment is basically the same as that in Example 1, except that the mass ratio of PEG-MoS2 to CeO2-NPs is 1:0.2.

[0058] Comparative Example 1

[0059] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that the mass ratio of PEG-MoS2 to CeO2-NPs is 1:0.1.

[0060] Comparative Example 2

[0061] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that the mass ratio of PEG-MoS2 to CeO2-NPs is 1:6.

[0062] Comparative Example 3

[0063] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that the nano cerium oxide particles are unmodified commercially available nano cerium oxide particles purchased from Shandong Desheng New Materials Co., Ltd., and the prepared material is recorded as CeO2-MoS2 (A).

[0064] Comparative Example 4

[0065] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that: in the synthesis process of CeO2-NPs, the amount of ammonium cerium nitrate used is 1.53 g, and the prepared material is recorded as CeO2-MoS2 (B).

[0066] Comparative Example 5

[0067] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that: in the synthesis process of CeO2-NPs, the amount of ammonium cerium nitrate used is 4.22 g, and the prepared material is recorded as CeO2-MoS2(C).

[0068] Comparative Example 6

[0069] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that during the synthesis of CeO2-NPs, the amount of sodium acetate added is 1 g, and the obtained material is recorded as CeO2-MoS2 (D).

[0070] Comparative Example 7

[0071] The preparation method of the rare earth growth factor in this comparative example is basically the same as that in Example 1, except that during the synthesis of CeO2-NPs, the amount of sodium acetate added is 15 g, and the obtained material is recorded as CeO2-MoS2 (E).

[0072] Test Example 1 Salicylic Acid Colorimetric Method for Testing the Active Oxygen Scavenging Ability of Rare Earth Growth Factor

[0073] 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 taken and added to the ferrous sulfate heptahydrate solution for reaction for 10 min to obtain active oxygen; the rare earth growth factor materials according to Examples 1 to 6 and Comparative Examples 1 to 7 were added to the reaction system at the same concentration to react with the active oxygen; and the absorbance at 510 nm was tested by an ultraviolet spectrophotometer at 0 min and 60 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.

[0074] The test results of the UV spectrophotometer at 0min and 60min after the rare earth growth factor material and the active oxygen were mixed 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, and compared with the blank group, the absorbance at 510nm of the samples added with rare earth growth factor materials decreased to varying degrees, and tended to decrease with the extension of time. The best effect was the CeO2-MoS2 material obtained by compounding at a mass ratio of 1:2, which can inhibit the generation of active oxygen in the environment for a long time.

[0075] Table 1 Absorbance of rare earth growth factor materials at an ultraviolet wavelength of 510 nm after contact with active oxygen for different time periods

[0076]

[0077]

[0078] Test Example 2 Particle size test of CeO2-MoS2 material

[0079] The rare earth growth factor material prepared in Example 1 was analyzed for particle size using a Malvern particle size tester. The results are as follows: Figure 1 As shown, the particle size distribution range is mainly around 1 μm, and it has antioxidant and free radical scavenging properties, can well promote wound healing, and meets the requirements as a growth factor dressing.

[0080] Application Example 1

[0081] First, a solution containing 10% sodium carboxymethyl cellulose (CMC-Na) and 8% polyvinyl alcohol (PVA) was prepared, and dissolved at a constant temperature of 80°C. After dissolution, 60 parts were taken as solution A, and rubber and paraffin oil were taken in a ratio of 1:2.5, and 30 parts of the mixture of the two were taken, and 1.0% of the functional rare earth growth factor prepared in Example 1 was added, and then stirred continuously, and the rubber was dissolved in the paraffin oil to obtain a mixed solution of the two as solution B. The B solution was quickly poured into the A solution, and the two were stirred continuously to fully mix, and the total dosage of the mixed solution was adjusted, and 5 parts of a mixture of sodium bicarbonate and citric acid (molar ratio 2:1) were added, and stirred at 120°C for 20 minutes. After the solution was slightly cooled, an appropriate amount was applied to a 10cm×10cm anti-adhesive film, with a weight of about 10g / piece, and frozen in a refrigerator at -26°C for 12h, and thawed at room temperature for 12h, that is, a complete freeze-thaw cycle, to obtain a medical dressing.

[0082] Application Example 2

[0083] The difference from Application Example 1 is that 0.5% by weight of the functional rare earth growth factor prepared in Example 1 is added.

[0084] 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 functional rare earth growth factor, characterized in that: The rare earth growth factor comprises PEG-MoS2 and nano-cerium oxide particles CeO2-NPs in a mass ratio of 1:(0.2-5), wherein the PEG-MoS2 is a solid phase material with polyethylene glycol modified on the surface, and the solid phase material is MoS2.

2. The functional rare earth growth factor according to claim 1, characterized in that: The preparation method of PEG-MoS2 comprises the following steps: using polyethylene glycol as a surface modification material, modifying the surface of MoS2 with polyethylene glycol through a heterogeneous solid-liquid reaction under heating reflux conditions, and finally obtaining PEG-MoS2.

3. The functional rare earth growth factor according to claim 2, characterized in that: The preparation method of the PEG-MoS2 comprises the following steps: Take a molybdenum source compound and thiourea, add polyethylene glycol and a solvent, then heat and continue heating under reflux and stirring at 80-100°C for 12-24 hours, wait for the reaction to be completed, dry and grind to obtain a powder material PEG-MoS2; Preferably, the molybdenum source compound is one or a mixture of two or more of ammonium molybdate, molybdenum pentachloride, and molybdenum oxide; Preferably, the mass ratio of the molybdenum source compound to thiourea is 1:(1-4); Preferably, the volume ratio of the polyethylene glycol to the solvent is 1:(10-20); Preferably, the solvent is deionized water.

4. The functional rare earth growth factor according to claim 1, characterized in that: The preparation method of nano cerium oxide particles CeO2-NPs comprises the following steps: adding a cerium source compound to a buffer solution to obtain a reaction solution, performing a hydrothermal reaction at 180-220° C. after the reaction solution is completely dissolved, standing and centrifuging after the reaction is completed, and collecting the precipitate after centrifugation to obtain nano cerium oxide particles CeO2-NPs; Preferably, the concentration of the cerium source compound in the reaction solution is 0.05-0.1 mol / L; Preferably, the cerium source compound is one or a mixture of two or more of ammonium cerium nitrate, cerium chloride heptahydrate, and cerium carbonate.

5. The functional rare earth growth factor according to claim 4, characterized in that: The buffer solution is an aqueous solution containing sodium acetate and acetic acid, and the mass ratio of sodium acetate to acetic acid in the buffer solution is 1:(1-3).

6. The functional rare earth growth factor according to claim 4, characterized in that: The mass concentration of the buffer solution is 30%-50%.

7. A method for preparing the functional rare earth growth factor according to any one of claims 1 to 6, characterized in that: The steps include: S1: Preparation of PEG-MoS2: Take a molybdenum source compound and thiourea, add polyethylene glycol and a solvent, then heat up, and continue heating under reflux and stirring at 80-100°C for 12-24 hours. After the reaction is completed, dry and grind to obtain a powder material PEG-MoS2; S2: Preparation of CeO2-NPs: The cerium source compound is added to the buffer solution, and after the mixed solution is completely dissolved, a hydrothermal reaction is carried out at 180-220° C. After the reaction is completed, the mixture is allowed to stand and centrifuged, and the precipitate after centrifugation is collected to obtain nano-cerium oxide particles CeO2-NPs; S3: Preparation of functional rare earth growth factors: PEG-MoS2 and CeO2-NPs are mixed and ground to obtain functional rare earth growth factors.

8. A medical dressing, comprising the functional rare earth growth factor according to any one of claims 1 to 6.

9. The medical dressing according to claim 8, characterized in that: The added mass of the functional rare earth growth factor is 0.5%-1.0%.

10. A method for preparing the medical dressing according to claim 8 or 9, characterized in that: The steps include: (1) dissolving the sodium carboxymethyl cellulose solution and the polyvinyl alcohol solution at a constant temperature, and the dissolved solution is determined as solution A; (2) taking rubber and paraffin oil and adding the functional rare earth growth factor, and then stirring and dissolving, the obtained mixed solution is solution B; (3) Pour solution B into solution A and stir continuously to fully mix the two. Adjust the total dosage of the mixed solution and add a mixture of sodium bicarbonate and citric acid and heat and stir. (4) After the solution of step (3) is cooled, it is applied to an anti-adhesive film and subjected to a freeze-thaw cycle to obtain a medical dressing.

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