Curcumin carbon dots as well as preparation method and application thereof

Abstract

The invention relates to the technical field of preparation of curcumin carbon dots, in particular to a curcumin carbon dot as well as a preparation method and application thereof. Curcumin and citric acid are mixed according to a specific mass ratio and calcined at 120-210 DEG C under the protection of inert gas, so that the nano material with excellent water solubility and curcumin active structure is successfully constructed. The preparation level is high, the reaction time is shortened, the process controllability is high, and the yield is improved; in an application level, the obtained curcumin carbon dots have relatively strong scavenging capacity on hydroxyl radicals, can effectively relieve oxidative stress caused by uranium exposure, and can remarkably improve kidney and multiple organ injuries caused by uranium in an animal model; the invention provides a brand-new nano treatment scheme for solving the problems that the existing uranium poisoning treatment medicine is poor in targeting property and limited in repair effect.

Description

Technical Field

[0001] This invention relates to the field of curcumin carbon dot preparation technology, specifically to a curcumin carbon dot, its preparation method, and its application. Background Technology

[0002] Curcumin carbon dots are zero-dimensional nanomaterials with fluorescence properties, typically smaller than 10 nanometers in size, formed through a carbonization process using natural curcumin as the main carbon source precursor. This type of material aims to combine the inherent bioactivity of curcumin (such as antioxidant and anti-inflammatory properties) with the excellent water solubility, biocompatibility, and ease of functionalization of carbon nanomaterials, thereby overcoming the problems encountered in the practical application of curcumin raw materials.

[0003] Currently, the most common method for preparing curcumin carbon dots in existing technologies is the hydrothermal method. This method is usually carried out in a high-temperature and high-pressure reactor. The reaction cycle is long (usually more than 8 to 12 hours), energy consumption is high, and the uniformity of reaction conditions (such as temperature and pressure) is difficult to control precisely. This results in large fluctuations in the quality and performance of different batches of products, which seriously restricts the feasibility of its large-scale production and clinical application.

[0004] Uranium, a chemically toxic and radioactive heavy metal, can cause severe tissue damage in the human body, particularly irreversible toxicity to the kidneys, and can also affect multiple organs such as the liver and spleen. The pathological mechanism of uranium poisoning is complex, involving multiple factors including direct cytotoxicity, oxidative stress damage, and inflammatory responses. Currently, clinical treatments for uranium poisoning are very limited, mainly relying on traditional heavy metal chelating agents (such as dimercaprol and EDTA). However, these drugs suffer from poor targeting, high nephrotoxicity risk, the need for early administration, and limited effectiveness in repairing existing tissue damage. There are currently no reports on the use of curcumin carbon dots in the preparation of drugs to prevent and treat uranium-induced damage. Summary of the Invention

[0005] This application addresses the technical problems of existing curcumin carbon dot preparation processes (such as hydrothermal methods), including long reaction cycles, high energy consumption, poor batch stability, and the lack of efficient drugs capable of repairing tissue damage in the field of uranium poisoning prevention and treatment. It provides a curcumin carbon dot, its preparation method, and its applications. Curcumin and citric acid are mixed at a specific mass ratio and calcined at 120℃–210℃ for a short time (2–4 hours) under inert gas protection, successfully constructing nanomaterials with both excellent water solubility and curcumin's active structure. In terms of preparation, the reaction time is shortened, the process is highly controllable, and the yield is increased to approximately 50%. In terms of application, the obtained curcumin carbon dots can effectively scavenge superoxide anions and reactive oxygen species in cells, maintain mitochondrial membrane potential stability, significantly alleviate oxidative stress induced by uranium exposure, and significantly improve uranium-induced kidney and multi-organ damage in animal models. This provides a novel nanotherapy strategy to solve the problems of poor targeting and limited repair effects of existing uranium poisoning treatments.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] The first aspect of the present invention provides a method for preparing curcumin carbon dots, comprising the following steps: mixing curcumin with citric acid, calcining the mixture in a tube furnace under inert gas protection, and obtaining the curcumin carbon dots after cooling.

[0008] Furthermore, the mass ratio of curcumin to citric acid is 1:(0.2-0.5).

[0009] Furthermore, the inert gas is nitrogen or argon, and the gas flow rate is 50 mL / min-100 mL / min.

[0010] Furthermore, the heating rate of the calcination reaction is 5℃ / min-10℃ / min.

[0011] Furthermore, the calcination reaction temperature is 120℃-210℃, and the calcination time is 2h-4h.

[0012] A second aspect of the present invention provides a method for preparing curcumin carbon dots as described above.

[0013] A third aspect of the present invention provides the application of the curcumin carbon dots described above or the curcumin carbon dots prepared by the above preparation method in the preparation of a drug for preventing and treating uranium-induced damage.

[0014] Furthermore, the application of curcumin carbon dots in the preparation of drugs to prevent uranium-induced damage.

[0015] A fourth aspect of the present invention provides a medicament for preventing uranium-induced damage, wherein the active ingredient is the curcumin carbon dots described above or the curcumin carbon dots prepared by the above preparation method.

[0016] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0017] This invention provides a curcumin carbon dot, its preparation method, and its application. Curcumin and citric acid are mixed at a specific mass ratio and calcined at 120℃–210℃ for a short time (2–4 hours) under inert gas protection, successfully constructing a nanomaterial possessing both excellent water solubility and the active structure of curcumin. In terms of preparation, the reaction time is shortened, the process is highly controllable, and the yield is increased to approximately 50%. In terms of application, the obtained curcumin carbon dots exhibit strong scavenging ability against hydroxyl radicals and can effectively alleviate oxidative stress induced by uranium exposure. In animal models, they significantly improve uranium-induced kidney and multi-organ damage, providing a novel nanotherapy strategy to address the problems of poor targeting and limited repair effects of existing uranium poisoning treatments. Attached Figure Description

[0018] Figure 1 The structural characterization diagram of curcumin carbon dots; Figure 1 In the figure, 'a' represents the TEM images, appearance images, and Tyndall effect of curcumin carbon dots at different calcination temperatures. Figure 1 b in the image represents the infrared characterization of curcumin and each curcumin carbon dot. Figure 1 c in the image represents the UV characterization of curcumin and its carbon dots. Figure 1 In the figure, d represents the XRD characterization of curcumin and each curcumin carbon point.

[0019] Figure 2 This is a graph showing the effect of curcumin carbon dots on cell viability under uranium exposure.

[0020] Figure 3 This study aimed to assess the scavenging effects of curcumin carbon dots on intracellular superoxide anions and reactive oxygen species, as well as their role in maintaining mitochondrial stability. Figure 3 In the figure, 'a' represents the DCF, DHE, and JC-1 fluorescence images of HK-2 cells exposed to 600 μM uranium after treatment with curcumin, CCDs-120, and CCDs-210; Figure 3 In this context, b represents the quantitative value of DCF fluorescence intensity for each group; Figure 3 In this context, 'c' represents the quantitative value of DHE fluorescence intensity for each group. Figure 3 In the figure, d represents the ratio of fluorescence intensity of JC-1 polymers (J-aggregates) to JC-1 monomers (monomers) in each group.

[0021] Figure 4 A graph showing the protective effect of curcumin carbon dots against uranium-induced kidney damage in vivo; Figure 4In the figure, 'a' represents the serum liver and kidney function (Crea, Urea), inflammatory markers (TNF-α, IL-6, IL-1β), and oxidative stress markers (SOD, GSH, MDA) of the curcumin and CCDs-120 and CCDs-210 groups. Figure 4 In the image, b represents HE, PAS staining, and TEM images of kidney tissue from the curcumin, CCDs-120, and CCDs-210 groups.

[0022] Figure 5 This is a graph showing the ameliorative effect of curcumin carbon dots on uranium-induced pathological damage to multiple organ tissues. Detailed Implementation

[0023] The present invention will now be described in detail with reference to the accompanying drawings.

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0025] The first aspect of this embodiment provides a method for preparing curcumin carbon dots, comprising the following steps: mixing curcumin with citric acid, calcining the mixture in a tube furnace under inert gas protection, and obtaining the curcumin carbon dots after cooling.

[0026] In some embodiments, the mass ratio of curcumin to citric acid is 1:(0.2-0.5). Reasonably controlling the mass ratio of curcumin to citric acid can better ensure the water solubility, stability, and effectiveness in preventing uranium-induced damage of the curcumin carbon point product. For example, the mass ratio of curcumin to citric acid is 1:0.2. The mass ratio of curcumin to citric acid is 1:0.3. The mass ratio of curcumin to citric acid is 1:0.4. Or, the mass ratio of curcumin to citric acid is 1:0.5.

[0027] In some embodiments, the inert gas is nitrogen or argon, and the gas flow rate is 50 mL / min to 100 mL / min. For example, the gas flow rate is 50 mL / min, 60 mL / min, 70 mL / min, 80 mL / min, or 90 mL / min, 100 mL / min.

[0028] In some embodiments, the heating rate of the calcination reaction is 5°C / min to 10°C / min. For example, the heating rate of the calcination reaction is 5°C / min, 6°C / min, 7°C / min, 8°C / min, 9°C / min, or 10°C / min.

[0029] In some embodiments, the calcination reaction temperature is 120℃-210℃, and the calcination time is 2h-4h. For example, the calcination reaction temperature is 120℃, 130℃, 140℃, 150℃, 160℃, 170℃, 180℃, 190℃, 200℃, or 210℃. The calcination reaction time is, for example, 2h, 3h, or 4h. Studies have found that the calcination reaction temperature and time are key factors affecting product performance. Reasonable control of the calcination process parameters can better ensure the water solubility, stability, and uranium-induced damage prevention effect of curcumin carbon point products.

[0030] The second aspect of this embodiment provides curcumin carbon dots prepared by the above-described method for preparing curcumin carbon dots.

[0031] The third aspect of this embodiment provides the application of the curcumin carbon dots described above or the curcumin carbon dots prepared by the above preparation method in the preparation of drugs for preventing and treating uranium-induced damage.

[0032] In some embodiments, the use of curcumin carbon dots in the preparation of drugs for preventing uranium-induced damage.

[0033] The fourth aspect of this embodiment provides a drug for preventing uranium-induced damage, wherein the active ingredient is the curcumin carbon dots described above or the curcumin carbon dots prepared by the above preparation method.

[0034] To better understand the above technical solutions, the following more detailed embodiments are provided for further explanation.

[0035] Example 1

[0036] Curcumin and citric acid were mixed at a mass ratio of 1:0.3 and calcined in a tube furnace under nitrogen protection (gas flow rate of 50 mL / min). The heating rate was 10 °C / min, the calcination temperature was 120 °C, and the calcination time was 4 h. After cooling, curcumin carbon dots were obtained.

[0037] Example 2

[0038] Curcumin and citric acid were mixed at a mass ratio of 1:0.3 and calcined in a tube furnace under nitrogen protection (gas flow rate of 50 mL / min). The heating rate was 10 °C / min, the calcination temperature was 150 °C, and the calcination time was 4 h. After cooling, curcumin carbon dots were obtained.

[0039] Example 3

[0040] Curcumin and citric acid were mixed at a mass ratio of 1:0.3 and calcined in a tube furnace under nitrogen protection (gas flow rate of 50 mL / min). The heating rate was 10 °C / min, the calcination temperature was 180 °C, and the calcination time was 4 h. After cooling, curcumin carbon dots were obtained.

[0041] Example 4

[0042] Curcumin and citric acid were mixed at a mass ratio of 1:0.3 and calcined in a tube furnace under nitrogen protection (gas flow rate of 50 mL / min). The heating rate was 10 °C / min, the calcination temperature was 210 °C, and the calcination time was 4 h. After cooling, curcumin carbon dots were obtained.

[0043] The curcumin carbon dots prepared in Examples 1-4 were characterized in structure and tested in performance.

[0044] Weigh out the uncalcined curcumin raw material as a comparative example (hereinafter referred to as free curcumin).

[0045] Preparation and characterization of curcumin carbon dots

[0046] like Figure 1 As shown, the prepared carbon dots exhibit a gradual color change from orange-yellow to brown with increasing calcination temperature, significantly improved water solubility, and a strong Tyndall effect. TEM characterization results show that the carbon dots have uniform particle size (2-4 nm) and good dispersion, with a distinct lattice structure. Infrared, ultraviolet, and XRD characterizations confirm the successful synthesis of the carbon dots.

[0047] In vitro uranium protection and antioxidant activity

[0048] like Figure 2 The effect of curcumin carbon dot concentration after calcination at different temperatures on the viability of TCMK-1 cells exposed to 600 μM uranium is shown. At concentrations of 1.25 and 2.5 μg / mL, the anti-uranium activity of carbon dots was significantly higher than that of the free curcumin group, with CCDs-120 and CCDs-210 showing the best effects. CCDs-210 also exhibited good anti-uranium activity at concentrations of 5 and 10 μg / mL.

[0049] like Figure 3 As shown, based on the CCK-8 results, CCDs-120 and CCDs-210 were selected for subsequent experiments. The applicant further discovered that CCDs-120 and CCDs-210 can effectively remove ROS generation and alleviate uranium-induced oxidative stress, demonstrating the great potential of curcumin carbon dots in the treatment of uranium-induced kidney injury.

[0050] In vivo uranium prevention effect

[0051] like Figure 4As shown, in vivo results (liver and kidney function, oxidative stress indicators, and inflammatory indicators) showed that both free curcumin and curcumin carbon dots could improve uranium-induced kidney damage, but the carbon dot group was more effective, and CCDs-210 was significantly better than CCDs-120.

[0052] like Figure 5 As shown, the major organ H&E results indicate that uranium causes significant damage not only to the kidneys but also to the heart, liver, spleen, and lungs. Both free curcumin and curcumin carbon dots significantly improved uranium-induced organ damage, but the carbon dot group was still more effective, and CCDs-210 was significantly superior to CCDs-120.

[0053] This invention successfully constructs nanomaterials possessing both excellent water solubility and the active structure of curcumin by mixing curcumin and citric acid in a specific mass ratio and calcining them at 120℃–210℃ for a short time (2–4 hours) under inert gas protection. In terms of preparation, the reaction time is shortened, the process is highly controllable, and the yield is increased to approximately 50%. In terms of application, the obtained curcumin carbon dots have a strong scavenging ability against hydroxyl radicals and can effectively alleviate oxidative stress induced by uranium exposure. In animal models, it significantly improves uranium-induced kidney and multi-organ damage, providing a novel nanotherapy strategy to address the problems of poor targeting and limited repair effects of existing uranium poisoning treatments.

[0054] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing curcumin carbon dots, characterized in that, Includes the following steps: Curcumin and citric acid are mixed and calcined in a tube furnace under inert gas protection. After cooling, the curcumin carbon dots are obtained.

2. The method for preparing curcumin carbon dots according to claim 1, characterized in that, The mass ratio of curcumin to citric acid is 1:(0.2-0.5).

3. The method for preparing curcumin carbon dots according to claim 1, characterized in that, The inert gas is nitrogen or argon, and the gas flow rate is 50 mL / min-100 mL / min.

4. The method for preparing curcumin carbon dots according to any one of claims 1-3, characterized in that, The heating rate of the calcination reaction is 5℃ / min-10℃ / min.

5. The method for preparing curcumin carbon dots according to claim 4, characterized in that, The calcination reaction temperature is 120℃~210℃.

6. The method for preparing curcumin carbon dots according to claim 5, characterized in that, The calcination time is 2 to 4 hours.

7. Curcumin carbon dots prepared by the method described in any one of claims 1-6.

8. The application of curcumin carbon dots according to claim 7 or curcumin carbon dots prepared by any of the preparation methods according to claims 1-6 in the preparation of drugs for preventing and treating uranium-induced damage.

9. The application according to claim 8, characterized in that, Application of curcumin carbon dots in the preparation of drugs to prevent uranium-induced damage.

10. A drug for preventing uranium-induced damage, characterized in that, Its active ingredient is the curcumin carbon dots as described in claim 7 or the curcumin carbon dots prepared by any of the preparation methods described in claims 1-6.

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