Use of cobalt phosphide in preparation of drugs for relieving inflammation
By preparing photothermally responsive hollow polyhedral cobalt phosphide nanoparticles, the problem of difficult ROS removal in existing technologies has been solved, enabling effective treatment of inflammatory diseases such as psoriasis, and exhibiting highly efficient anti-inflammatory and antibacterial effects.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- XIAMEN UNIV
- Filing Date
- 2024-12-31
- Publication Date
- 2026-06-30
AI Technical Summary
Existing technologies are insufficient to effectively eliminate reactive oxygen species (ROS), leading to persistent flare-ups of inflammatory diseases such as psoriasis. Furthermore, conventional treatments have side effects and allergic reactions, making it difficult to meet clinical needs.
Hollow polyhedral cobalt phosphide nanoparticles with photothermal response possess enzyme-like catalytic activities such as peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD). They can be used to prepare anti-inflammatory drugs, scavenge various reactive oxygen species, inhibit bacterial growth through photothermal properties, and promote tissue repair.
Cobalt phosphide nanoparticles significantly scavenge ROS, inhibit inflammatory responses, improve inflammatory conditions such as psoriasis, restore normal tissue healing, and possess good antibacterial ability and biosafety, providing a new approach to anti-inflammatory treatment.
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Figure CN122297518A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical preparations, and more particularly to the use of cobalt phosphide in the preparation of anti-inflammatory drugs. Background Technology
[0002] Psoriasis is a common chronic inflammatory skin disease characterized by dry, itchy skin, erythema, and silvery scales. Its histopathological features primarily include thickening of the stratum corneum and extensive infiltration of inflammatory cells at the dermal-epidermal junction, accompanied by vasodilation. Psoriasis is often accompanied by various complications, such as cardiovascular disease, arthritis, and depression, severely impacting patients' physical health and quality of life. Current conventional treatments for psoriasis, such as corticosteroids, vitamin D analogs, and calcineurin inhibitors, while effective to some extent, may cause side effects and allergic reactions with long-term use, making them insufficient to fully meet current clinical needs.
[0003] Reactive oxygen species (ROS) are a class of highly chemically active oxidizing substances, including superoxide anions, hydrogen peroxide, and hydroxyl radicals. ROS not only regulate cell proliferation, differentiation, and apoptosis as signaling molecules, but also play a central regulatory role in inflammatory signal transduction. At physiological concentrations, ROS are crucial for regulating cellular redox signals and maintaining normal cellular processes. However, in the epithelial immune microenvironment (EIME), the psoriatic inflammatory cascade is closely related to an imbalance in ROS regulation among keratinocytes (KCs) and immune cells. When ROS production exceeds the scavenging capacity of the antioxidant system, oxidative stress is triggered, disrupting the dynamic balance of the EIME and leading to persistent inflammation.
[0004] Given the harmful effects of excessive ROS, developing therapeutic strategies targeting ROS clearance has become an important means of alleviating inflammation. In recent years, nanozymes have shown significant potential in the treatment of inflammatory diseases due to their diverse enzymatic activities, such as rheumatoid arthritis, Parkinson's disease, and wound healing in diabetes. Nanozymes effectively clear ROS through superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)-like activities. Simultaneously, their nanomaterial properties can enhance drug absorption and diffusion at the skin barrier, prolonging drug retention time at the target site. However, current therapeutic methods for ROS clearance are relatively limited, making effective ROS regulation difficult. Therefore, developing a safe and highly effective therapeutic drug to clear ROS is crucial for solving the challenges in psoriasis treatment. Summary of the Invention
[0005] The purpose of this invention is to address the aforementioned problems in the prior art and provide an application of cobalt phosphide in the preparation of anti-inflammatory drugs. This invention synthesizes photothermally responsive hollow polyhedral cobalt phosphide nanoparticles, which possess enzyme-like catalytic activities such as peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD), as well as the ability to scavenge hydroxyl radicals (·OH), making them a broad-spectrum ROS scavenger. This material not only significantly alleviates inflammatory responses but also inhibits bacterial growth at the site of inflammatory wounds through its excellent photothermal properties and accelerates tissue repair by promoting local oxygen production. Therefore, this invention is expected to effectively improve inflammatory conditions and restore normal wound healing.
[0006] To achieve the above objectives, the present invention adopts the following technical solution:
[0007] An application of cobalt phosphide in the preparation of anti-inflammatory drugs, wherein the cobalt phosphide is used to prepare anti-inflammatory drugs by virtue of its broad-spectrum reactive oxygen species scavenging ability and photothermal properties.
[0008] The inflammations mentioned include psoriasis, lupus, hepatitis, nephritis, arthritis, pneumonia, and pancreatitis.
[0009] The cobalt phosphide has a hollow polyhedral structure, such as a dodecahedral structure.
[0010] The method for preparing cobalt phosphide includes the following steps:
[0011] 1) Co(NO3)2·6H2O and 2-methylimidazole were separately dispersed in methanol solution, mixed, heated and stirred, and then collected and washed after standing to obtain the precursor;
[0012] 2) Place the precursor obtained in step 1) in a tube furnace and carbonize it under a protective atmosphere. Place the carbonized sample and NaH2PO2 at opposite ends of the crucible, heat it under a protective atmosphere, and then seal it for phosphating.
[0013] In step 1), the heating and stirring temperature is 24~70℃, and the time is 0.5~24h.
[0014] In step 2), the carbonization conditions are 400~800℃ for 0.5~4h.
[0015] In step 2), the phosphating conditions are 350~700℃ for 0.5~6 h.
[0016] In step 2), the mass ratio of sample to NaH2PO2 is 1:0.5~30.
[0017] In step 2), the mass ratio of Co(NO3)2·6H2O to 2-methylimidazole is 1:0.1~10.
[0018] Compared with the prior art, the beneficial effects achieved by the technical solution of this invention are:
[0019] The cobalt phosphide of this invention has high activity of multiple antioxidant enzymes, including POD, CAT and SOD enzyme-like catalytic activity, and can scavenge various reactive oxygen species, including hydroxyl radicals, superoxide anions and hydrogen peroxide.
[0020] Furthermore, cobalt phosphide exhibits a photothermal conversion efficiency of up to 68%, and its antibacterial activity, utilizing the photothermal effect, reaches over 90% under photothermal irradiation conditions at a dosage of 300 μg / ml. Moreover, under near-infrared light irradiation, the antioxidant enzyme activity of CoP is also enhanced, especially POD enzyme, with a 1.5-fold increase in activity at 50 μg / mL CoP.
[0021] At the cellular level, CoP exhibits protective capabilities against oxidative damage to macrophages and keratinocytes in the inflammatory microenvironment, including RAW264.7 mouse monocytes / macrophages and HaCaT immortalized human keratinocytes. Notably, when 808 nm near-infrared light irradiation is incorporated into the intracellular CoP-catalyzed ROS scavenging reaction, it further promotes the clearance of intracellular reactive oxygen species. Combined with immunofluorescence staining, ELISA, and RT-qPCR, CoP was found to have an inhibitory effect on inflammatory factors (such as TNF-α and IL-6).
[0022] Meanwhile, the anti-inflammatory mechanism of CoP was demonstrated through macrophage polarization experiments. In in vivo experiments, at a dose of 6 mg / kg, this nanoparticle drug group could improve the erythema, scaling, and stratum corneum thickening caused by vasodilation and inflammation in the subcutaneous layer of psoriasis on the back of mice, thereby alleviating the progression of psoriasis.
[0023] In summary, the cobalt phosphide of this invention exhibits different enzyme-like activities, excellent photothermal conversion properties, good antibacterial ability, good ability to scavenge intracellular reactive oxygen species and inflammatory factors, good biosafety, and anti-inflammatory properties. It can effectively exert anti-inflammatory effects, providing new ideas for improving anti-inflammatory treatment in clinical practice, especially in the application of anti-psoriasis treatment, and has important reference value and application prospects. Attached Figure Description
[0024] Figure 1 These are scanning electron microscope (SEM) images and transmission electron microscope (TEM) images of Example 1.
[0025] Figure 2 The SOD-like activity and corresponding [specific activity] of Example 2 Clearance rate; among which, Figure 2 The left figure shows the change of NBT characteristic absorption over time at different CoP concentrations. Figure 2The right figure shows the changes in characteristic absorption of NBT at different CoP concentrations at the 5th minute, and the calculated values are as follows: Clearance rate.
[0026] Figure 3 This refers to the CAT-like activity and corresponding H2O2 scavenging efficiency of Example 2; wherein, Figure 3 The left figure shows the oxygen content measured by gas chromatography. Figure 3 The figure on the right shows the H2O2 removal efficiency calculated based on gas chromatography data at different CoP concentrations.
[0027] Figure 4 This is a graph showing the peroxidase (POD) activity detection in Example 2, with the vertical axis representing the absorption of oxidized TMB.
[0028] Figure 5 It is Example 2 Clearing the activity map and detecting electron spin resonance (ESR) under different CoP concentrations. Signal strength.
[0029] Figure 6 This is a graph showing the photothermal properties of CoP under 808 nm laser irradiation in Example 3; where, Figure 6 The top left image shows thermal images of CoP solutions of different concentrations under 808nm laser irradiation. Figure 6 The top right image is... Figure 6 The data representation of the top left image Figure 6 The lower left figure shows the heating period (600s) and cooling period (600~1200s) of a 200μg / ml CoP solution under 808nm laser irradiation. Figure 6 The lower right figure shows the cycling diagram of a 200 μg / ml CoP solution under 808nm laser irradiation or without irradiation, demonstrating the thermal stability of CoP nanozymes.
[0030] Figure 7 This is a graph showing the photothermal antibacterial performance of CoP in Example 3.
[0031] Figure 8 It is aimed at Figure 7 The data statistics are presented as follows.
[0032] Figure 9 This is the effect of the photothermal properties of CoP on enzyme catalytic activity in Example 3; wherein, Figure 9 The left figure shows the POD-like enzyme activity of CoP under different CoP concentrations in the absence and presence of NIR light. Figure 9 The middle figure shows the ·OH scavenging ability of CoP under different CoP concentrations in the absence and presence of NIR light. Figure 9 The right figure shows the effect of different CoP concentrations on the effects of no NIR illumination and NIR illumination. Clearance rate.
[0033] Figure 10 This is the safety result of RAW267.4 macrophages and CoP at the HaCaT level in Example 4.
[0034] Figure 11 This is Example 4, which describes the RT-qPCR detection of inflammatory factors; wherein, Figure 11 The left figure shows the TNF-α expression level under the influence of CoP. Figure 11 The middle figure shows the expression level of IL-6 under the influence of CoP. Figure 11 The right figure shows the expression level of IL-8 mRNA under the action of CoP. The data shows that the expression of inflammatory factors is downregulated under the action of CoP.
[0035] Figure 12 This is a diagram showing the therapeutic effect of the mouse model of psoriasis in Example 5; wherein, Figure 12 The left image shows the subjective skin scores of mice in four groups: IMQ, IMQ+HA, IMQ+HA+CoP, and IMQ+HA+CoP+NIR. Figure 12 The right figure shows the changes in average body weight of mice in four groups: IMQ, IMQ+HA, IMQ+HA+CoP, and IMQ+HA+CoP+NIR.
[0036] Figure 13 This is a graph showing significant changes associated with psoriasis in the histopathological analysis of Example 5.
[0037] Figure 14 This is an immunohistochemical (IHC) staining image from Example 5.
[0038] Figure 15 This is a graph showing the mRNA expression levels of inflammatory factors detected by RT-qPCR in Example 5.
[0039] Figure 16 This is a biosafety evaluation diagram for Example 5. Detailed Implementation
[0040] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention and are not intended to limit the scope of protection of the present invention. In practical applications, the improvements and adjustments made by those skilled in the art based on the present invention still fall within the scope of protection of the present invention.
[0041] This invention first prepares CoP and then applies it in the biomedical field, mainly including its application in cell and animal models, specifically including the following:
[0042] Cellular applications: Evaluating the effects of cobalt phosphide on different cell types, including cytotoxicity, uptake efficiency, and its antioxidant and anti-inflammatory biological effects. Its intracellular biological activity can be analyzed through various cell experiments, such as the CCK-8 assay, flow cytometry, immunofluorescence staining, and ELISA.
[0043] Applications in animal models: Cobalt phosphide is used to study its therapeutic effects, mechanisms, and biosafety in animal models such as mice. Its therapeutic potential is tested using disease models (such as psoriasis), and its anti-inflammatory and antioxidant effects are analyzed at the gene and protein levels using techniques such as histology, immunohistochemistry, qPCR, and flow cytometry.
[0044] Biocompatibility and biosafety assessment: Using methods such as hemolysis test, histological staining, and ICP-MS, the residual metal and potential toxicity of cobalt phosphide in vivo were detected, and its biocompatibility and safety were assessed.
[0045] Example 1
[0046] The preparation steps of CoP in this embodiment include the following:
[0047] (1) 2.212 g of Co(NO3)2·6H2O was dispersed in 50 mL of methanol to prepare solution A, and 5.272 g of 2-methylimidazole was dispersed in 50 mL of methanol to prepare solution B. Solution A was quickly poured into solution B and stirred at 60 °C for 2 h. After standing overnight, the product was collected and washed to obtain ZIF-67 precursor.
[0048] (2) The ZIF-67 precursor obtained in step (1) was placed in a tube furnace and carbonized at 600℃ for 2 h under Ar protective atmosphere. The carbonized sample and NaH2PO2 were weighed and placed at both ends of the crucible with a mass ratio of 1:20. The end with NaH2PO2 was placed upstream. After heating to 400℃ under Ar, the vent and outlet were sealed and kept at 3 h for phosphating. After cooling to room temperature, the dodecahedral CoP was collected.
[0049] Figure 1 In the image, A is a scanning electron microscope (SEM) image of CoP. Figure 1 Image B in the image is a transmission electron microscope (TEM) image. The results show that the prepared CoP is relatively uniform with an average diameter of ≈300 nm and exhibits a regular dodecahedral morphology. These results indicate that phosphating calcination can successfully transform the ZIF-67 precursor into hollow CoP polyhedra without destroying the morphology.
[0050] Example 2
[0051] Investigation of the activities of various enzymes and photothermal properties of cobalt phosphide.
[0052] Figure 2 For CoP's SOD-like activity and corresponding Sweep rate. The effect of CoP on NBT photoreduction was evaluated by measuring the inhibition rate of NBT photoreduction. The scavenging ability was assessed. Riboflavin, cysteine, NBT, and CoP were dissolved in PBS at pH 7.4. The mixture was then irradiated under an LED screen for 5 minutes. After illumination, the reduction of NBT to the blue product at the 560 nm absorption peak was quantitatively determined using a spectrophotometer. The results showed that with increasing CoP concentration, the absorbance value decreased significantly, indicating that the SOD-like activity of CoP increased, contributing to a higher inhibition rate. Figure 2 The Control group is the PBS group.
[0053] Figure 3 This is a CAT-like activity profile of CoP. Evaluation was performed by measuring generated oxygen (O2) using gas chromatography, and illustrated by directly monitoring the change in the characteristic absorbance of H2O2 at 240 nm using a UV-Vis-NIR spectrophotometer. O2 bubbles were immediately observed upon the addition of CoP to H2O2, and the dissolved oxygen content increased significantly over time. Furthermore, the consumption of H2O2 was monitored using its characteristic absorption peak at 240 nm. The characteristic absorbance of CoP decreased significantly, demonstrating CoP's excellent H2O2 elimination ability. The Kc of CoP with the H2O2 substrate is also shown. m and V max 2.49 mM and This indicates that CoP has a strong affinity for H2O2. Kinetic analysis shows that CoP has a better affinity for the H2O2 substrate than natural CAT (K2O2). m ≈28.8mm).
[0054] Figure 4 To detect the peroxidase (POD) activity of CoP, natural 3,5,3',5'-tetramethylbenzidine (TMB, 1.5 mM) was typically used. The POD activity of CoP was studied in PBS buffer (pH = 4) containing 4 mM H₂O₂. As the reaction proceeded, the generated blue product reached its maximum absorbance at 652 nm. Changes in absorbance were continuously recorded using a spectrophotometer to assess the enzymatic activity of POD and the Kt of CoP to the substrate H₂O₂. m The value is 0.26 mM, V max for With horseradish peroxidase (K) mCompared to (2.2 mM), CoP has a lower Km, indicating that CoP has a higher affinity for the substrate H2O2.
[0055] Figure 5 The diagram shows the ·OH scavenging activity of CoP. For the electron spin resonance (ESR) method, the specific procedure is as follows: DMPO is used as a spin trap to capture Fe²⁺. + / H2O2 generated by the system It has a characteristic peak ratio of 1:2:2:1. The corresponding ESR spectrum was recorded for further verification. The removal effect. After adding CoP, The characteristic peaks gradually decrease in a concentration-dependent manner, eventually disappearing almost completely. The decrease in the signal intensity of the DMPO-OH adduct is related to... The reduction is related to the fact that CoP has a good ability to scavenge ROS, among which, Figure 5 The Control group was the PBS group, i.e., without PBS. The Fenton group is produced via the Fenton reaction. Group, that is, rich in Group.
[0056] Example 3
[0057] Verification of the photothermal properties and antibacterial effects of cobalt phosphide.
[0058] Figure 6 The image shows the photothermal properties of CoP under 808 nm laser irradiation. Infrared thermal imagers were used to record and monitor the photothermal properties of CoP aqueous solutions of different concentrations under 808 nm laser irradiation (1 W / cm²). 2 Photothermal performance under near-infrared (10 min) irradiation. Samples of different concentrations were irradiated for 10 min, and photothermal images of the samples at different concentrations were obtained, and real-time temperature change curves were plotted. According to the infrared thermal images, after 10 min of irradiation, the temperature of cobalt phosphide increased from 28℃ to 63.0℃, indicating the conversion of near-infrared radiation into heat. From the temperature rise curves of different CoP concentrations, it can be seen that under near-infrared laser irradiation, the control group without CoP showed no significant temperature change even after 10 min. Meanwhile, CoP showed a concentration-dependent temperature change, i.e., the temperature rise was proportional to the CoP concentration. Importantly, after four laser on / off cycles, laser irradiation for 10 minutes, and natural cooling, CoP retained its photothermal capacity, indicating excellent photothermal stability. The photothermal conversion efficiency of CoP reached 68%, demonstrating its superior photothermal conversion performance, higher than most available 808 nm photothermal agents.
[0059] Figure 7 and Figure 8To investigate the photothermal antibacterial properties of CoP, two typical pathogenic bacteria, Staphylococcus aureus and Escherichia coli, were selected as experimental strains. In the antibacterial test, Escherichia coli and Staphylococcus aureus were each divided into four groups: (1) a bacterial group as the control group; (2) bacteria + near-infrared (NIR); (3) bacteria + CoP; and (4) bacteria + CoP + NIR. In groups (2) and (4), the NIR wavelength was 808 nm and the light intensity was 1 W / cm². 2 Near-infrared light irradiation for 10 min; in groups (3) and (4), the final concentration of CoP was 300 μg / mL. The total volume of each tube of solution was 800 μL. 200 μL was taken and incubated overnight in a 96-well plate. 5 μL of the bacterial suspension was then taken and appropriately diluted in a square culture dish for incubation and counting. 40 μL of the remaining bacterial solution was then spread on an agar plate and inoculated at 37 ℃ for 24 h using the colony spreader method. The results showed that the bacterial colony groups in CoP were significantly different from those in the control group and the group irradiated by laser (808 nm, 1 W / cm²). 2 The decrease was slightly compared to the previous group, indicating a weaker bactericidal effect. However, the significant decrease in the CoP / NIR group suggests that the CoP-induced photothermal effect can effectively eliminate bacteria.
[0060] Figure 9 To investigate the effect of the photothermal properties of CoP on its enzyme-like catalytic activity, this section is divided into the following groups: (1) CoP; (2) CoP + NIR. Group (2) received 808 nm, 1 W / cm 2 Near-infrared light irradiation was performed. The final CoP concentrations were 10 μg / mL, 20 μg / mL, and 50 μg / mL. Combining the above methods for measuring different enzyme activities, the effect of photothermal properties on enzyme activity was compared based on the change in absorbance of the indicator with and without 808 nm near-infrared irradiation. The effect on POD enzyme activity of CoP was first investigated after near-infrared laser irradiation (1 W / cm²). 2 At a concentration of 50 μg / mL, the POD enzyme activity of CoP increased by 1.5 times (after 5 minutes); 808 nm near-infrared light also slightly improved the scavenging ability of CoP's ·OH groups, but the effect was not significant. Furthermore, near-infrared laser irradiation enhanced the scavenging of CoP. The ability of CoP at a concentration of 10 μg / mL The removal efficiency increased by about 2 times. This phenomenon is presumably due to the photothermal effect of cobalt phosphide, where the heat generated after absorbing light energy promotes the catalytic reaction.
[0061] Example 4
[0062] An investigation into the anti-inflammatory capabilities of cobalt phosphide in cells.
[0063] 1. Cytotoxicity of cobalt phosphide in cells
[0064] Figure 10 The cytotoxicity of different concentrations of CoP on RAW267.4 and HaCaT macrophages was investigated. To ensure the safe application of CoP, its intrinsic cytotoxicity in RAW264.7 and HaCaT cells was first assessed using the Standard Cell Counting Kit-8 (CCK-8) assay. CoP did not exhibit significant cytotoxicity at concentrations up to 50 μg / mL, and therefore can be used in subsequent cell experiments.
[0065] 2. Investigation of the anti-inflammatory ability of cobalt phosphide in cells
[0066] Figure 11 The expression levels of TNF-α, IL-6, and IL-8 mRNA were detected by RT-qPCR. Considering the key role of keratinocytes in the pathogenesis of psoriasis through the secretion of pro-inflammatory cytokines, the effect of CoP on TNF-α-induced inflammatory cytokine production in HaCaT cells was further evaluated. As shown in the figure, TNF-α stimulation led to increased levels of TNF-α, IL-6, and interleukin-8 (IL-8) in HaCaT cells, while CoP treatment significantly reduced the expression of these cytokines.
[0067] Example 5
[0068] Application of cobalt phosphide in in vivo inflammatory treatment (psoriasis).
[0069] Figure 12 To evaluate the therapeutic effect of CoP in a mouse model of psoriasis, an imiquimod (IMQ)-induced psoriasis-like mouse model was established, closely replicating the epidermal and histological features of human psoriasis plaques. After 6 days of topical application of IMQ cream, mice exhibited significant skin thickening, severe erythema, and extensive scaling on the back, confirming successful induction of the psoriasis model. A CoP solution in hyaluronic acid (HA) was applied daily to the IMQ-induced psoriasis lesions in mice. The hyaluronic acid component enhances skin hydration and promotes the retention of CoP in the hydrated epidermis, thus supporting the therapeutic effect. Mice were randomly assigned to 5 treatment groups: 1) PBS buffer control group; 2) IMQ-only psoriasis model group (i.e., negative control group); 3) IMQ+HA treatment group; 4) IMQ+HA+CoP treatment group; 5) IMQ+HA+CoP+NIR treatment group. As shown in the figure, CoP treatment significantly reduced desquamation and erythema in psoriasis mice. Mice treated with IMQ showed significantly elevated Psoriasis Area and Severity Index (PASI) scores, while CoP supplementation resulted in significant improvement in skin lesions and a decrease in PASI scores compared to the IMQ-based psoriasis model group. Figure 12 Left image), weight stable ( Figure 12 (Right image).
[0070] Figure 13 Histopathological analysis revealed significant changes associated with psoriasis. Hematoxylin and eosin (H&E) staining of IMQ-induced psoriasis mice showed marked epidermal hyperplasia, significant hyperkeratosis of the stratum corneum, and elongation of the reticular ridges in the dermis. CoP treatment significantly alleviated psoriatic inflammation, manifested as reduced epidermal thickness and decreased dermal infiltrating cells.
[0071] Figure 14 Immunohistochemical (IHC) staining showed increased expression of p-STAT3, CD3 (T cell marker), F4 / 80 (macrophage marker), PCNA-positive keratinocytes, CD103 (tissue memory T cell marker), and TNF-α in psoriatic lesions of the IMQ group. These markers were reduced after CoP treatment compared to the IMQ-treated psoriasis model group.
[0072] Figure 15 RT-qPCR was used to detect the mRNA expression levels of inflammatory factors. Analysis of the expression of pro-inflammatory cytokines, including Il-17a, Tnf-α, Il-12, Il-23, and Il-10, showed that CoP significantly downregulated their mRNA levels, indicating that CoP can effectively alleviate psoriatic inflammation.
[0073] Figure 16 This study evaluated the biosafety of CoP. The efficacy and safety of CoP treatment were comprehensively assessed. Histological examination of the skin and major organs (heart, lung, liver, spleen, and kidney) revealed no pathological changes. Furthermore, hemolysis tests showed that therapeutic doses of CoP did not induce hemolysis. These results highlight the excellent biosafety and biocompatibility of CoP in an IMQ-induced mouse model of psoriasis.
[0074] The embodiments described above provide a detailed explanation of the technical solutions and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, additions, and equivalent substitutions made within the scope of the principles of the present invention should be included within the protection scope of the present invention.
Claims
1. The application of cobalt phosphide in the preparation of anti-inflammatory drugs, characterized in that: Cobalt phosphide, with its broad-spectrum reactive oxygen species scavenging ability and photothermal properties, is used to prepare drugs that alleviate inflammation.
2. The application of cobalt phosphide as described in claim 1 in the preparation of anti-inflammatory drugs, characterized in that: The inflammations mentioned include psoriasis, lupus, hepatitis, nephritis, arthritis, pneumonia, and pancreatitis.
3. The application of cobalt phosphide as described in claim 1 in the preparation of anti-inflammatory drugs, characterized in that: The cobalt phosphide has a hollow polyhedral structure.
4. The application of cobalt phosphide as described in claim 1 in the preparation of anti-inflammatory drugs, characterized in that, The method for preparing cobalt phosphide includes the following steps: 1) Co(NO3)2·6H2O and 2-methylimidazole were separately dispersed in methanol solution, mixed, heated and stirred, and then collected and washed after standing to obtain the precursor; 2) Place the precursor obtained in step 1) in a tube furnace and carbonize it under a protective atmosphere. Place the carbonized sample and NaH2PO2 at opposite ends of the crucible, heat it under a protective atmosphere, and then seal it for phosphating.
5. The application of cobalt phosphide as described in claim 4 in the preparation of anti-inflammatory drugs, characterized in that: In step 1), the heating and stirring temperature is 24~70℃, and the time is 0.5~24h.
6. The application of cobalt phosphide as described in claim 4 in the preparation of anti-inflammatory drugs, characterized in that: In step 2), the carbonization conditions are 400~800℃ for 0.5~4h.
7. The application of cobalt phosphide as described in claim 4 in the preparation of anti-inflammatory drugs, characterized in that: In step 2), the phosphating conditions are 350~700℃ for 0.5~6 h.
8. The application of cobalt phosphide as described in claim 4 in the preparation of anti-inflammatory drugs, characterized in that: In step 2), the mass ratio of sample to NaH2PO2 is 1:0.5~30.
9. The application of cobalt phosphide as described in claim 4 in the preparation of anti-inflammatory drugs, characterized in that: In step 2), the mass ratio of Co(NO3)2·6H2O to 2-methylimidazole is 1:0.1~10.