Nano-sized iron-oxygen cluster compound drug molecule, preparation method and application of nano-sized iron-oxygen cluster compound drug molecule in preparation of sepsis treatment drug

Abstract

The invention discloses a nano-sized iron-oxygen cluster compound drug molecule, a preparation method and application of the nano-sized iron-oxygen cluster compound drug molecule in preparation of sepsis treatment drugs, and belongs to application of the nano-sized iron-oxygen cluster compound drug molecule in the aspect of disease treatment. The method comprises the following steps: sequentially adding ferric nitrate, L-(+)-tartaric acid and gadolinium nitrate into a magnesium acetate-acetic acid buffer solution, uniformly stirring, and then adding carbonate; and cooling to room temperature after water bath, filtering, carrying out evaporation culture on the obtained filtrate at 25 DEG C, and carrying out vacuum drying to obtain the nano-sized iron-oxygen cluster compound drug molecule. The nano-sized iron-oxygen cluster compound drug molecule prepared by the invention reduces the burden of blood and peritoneal fluid bacteria of a cecum ligation puncture mouse by activating B cells in the mouse body and increasing the natural antibody level, improves the liver injury and lung injury of the mouse, reduces the proportion of inflammatory factors and inflammatory cells in the mouse body, and improves the curative effect of the mouse. Therefore, the death rate of sepsis model mice is effectively reduced, the action effect is remarkable, and the traditional Chinese medicine composition has unique advantages in the application aspect of treating sepsis.

Description

Technical Field

[0001] The invention relates to the application of nanometer-sized iron-oxygen cluster drug molecules in treating diseases, and specifically relates to a nanometer-sized iron-oxygen cluster drug molecule (MIC), a preparation method and the application of the MIC in preparing drugs for treating sepsis. Background Art

[0002] Sepsis is a serious disease caused by infection with pathogens such as bacteria, fungi, viruses, and parasites, which causes systemic inflammatory response syndrome and multiple organ damage. At present, it is globally recognized that sepsis is a disease with a very high mortality rate among severe illnesses, which brings a serious burden to the medical field. The classic sepsis treatment recommended in the "Surviving Sepsis Campaign (SSC): International Guidelines for the Treatment of Sepsis and Septic Shock 2021 Edition" is to eliminate pathogens as soon as possible, so the timely and effective use of antibiotics is one of the main and most critical treatment options. However, the clinical treatment effect of antibiotics is far from achieving the effect of restoring body functions, and it will also cause the emergence of multidrug-resistant bacteria. Not only does it fail to achieve the expected effect, but it also increases the difficulty of treating sepsis with antimicrobial drugs. Summary of the invention

[0003] The purpose of the present invention is to provide a nano-sized iron-oxygen cluster compound (MIC) drug molecule, a preparation method and its application in the preparation of a drug for treating sepsis. The present invention stimulates B cells in an organism (mouse) to produce natural antibodies covering a variety of bacteria, thereby achieving the effect of significantly reducing inflammation and treating sepsis.

[0004] The present invention utilizes the combined technology of heating and constant temperature evaporation culture to obtain nano-sized iron-oxygen cluster drug molecules, realizes the simplicity of the preparation process and the synthesis of gram-level drugs, and is effectively applied in the treatment and relief of sepsis in mice.

[0005] The first object of the present invention is to provide a method for preparing nano-sized iron-oxygen cluster compound (MIC) drug molecules, the steps of which are as follows:

[0006] (1) In a magnesium acetate-acetic acid buffer solution, ferric nitrate, L-(+)-tartaric acid (CAS: 87-69-4, molecular formula: C4H6O6, structural formula shown below) and gadolinium nitrate are added in sequence, stirred evenly, and then carbonate (one of lanthanum carbonate, neodymium carbonate, cerium carbonate, and gadolinium carbonate) is added thereto to obtain a mixed solution, wherein the molar ratio of ferric nitrate, L-(+)-tartaric acid, gadolinium nitrate and carbonate is 10:6:1:1, and the concentration of ferric nitrate in the magnesium acetate-acetic acid buffer solution is 0.05 to 0.2 mol / L;

[0007]

[0008] (2) heating the mixed solution obtained in step (1) in a water bath at 90 to 98° C. for 2 to 4 hours, filtering the mixed solution after it cools to room temperature, and evaporating and culturing the obtained filtrate at room temperature for 2 to 3 weeks to obtain an iron-oxygen cluster drug molecule in the form of a red block or red powder;

[0009] (3) The iron-oxygen cluster drug molecules obtained in step (2) are vacuum dried at 50-70° C. to obtain the nano-sized iron-oxygen cluster drug molecules (MIC).

[0010] The second object of the present invention is to provide a nano-sized iron-oxygen cluster compound (MIC) drug molecule, which is prepared by the above method.

[0011] The third object of the present invention is to provide the use of the above-mentioned nano-sized iron-oxygen cluster compound (MIC) drug molecule in the preparation of drugs for treating sepsis.

[0012] Beneficial effects of the present invention

[0013] 1. The present invention can realize the synthesis and preparation of nano-sized iron-oxygen cluster compound (MIC) drug molecules, and the sample is in the form of red blocks or red powder; and the method of the present invention can quickly synthesize gram-level iron-oxygen cluster compound drug molecules, and has the characteristics of simple and easy preparation method, high yield, good repeatability and easy large-scale preparation;

[0014] 2. The nano-sized iron-oxygen cluster compound (MIC) drug molecule prepared by the present invention activates B cells in mice, increases the level of natural antibodies, reduces the bacterial burden in the blood and peritoneal fluid of mice with cecal ligation and puncture, improves liver damage and lung damage in mice, and reduces the proportion of inflammatory factors and inflammatory cells in mice, thereby effectively reducing the mortality rate of sepsis model mice. The effect is significant and has unique advantages in the treatment of sepsis. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The crystal structure of MIC prepared in Example 1;

[0016] Figure 2 The crystal structure simulation XRD data of MIC prepared in Example 1 (lower curve) and the experimental test XRD data of the synthesized sample (upper curve);

[0017] Figure 3 The infrared (IR) image of the MIC prepared in Example 1;

[0018] Figure 4The MIC prepared in Example 1 is used for the comparison of inflammatory changes in mice after injection. The ordinate of the left figure is the content of IL-4 (interleukin-4), and the ordinate of the right figure is the content of IL-6 (interleukin-6), which is obtained by Elisa kit testing. Among them, IL-4 (interleukin-4) represents an anti-inflammatory cytokine, and IL-6 (interleukin-6) represents a pro-inflammatory cytokine. CLP represents the sepsis model group of cecal ligation and puncture surgery: that is, the cecum of the mouse is ligated by laparotomy, and the cecum is put back into the mouse body after perforation, thereby inducing abdominal infection in mice, which is called the sepsis model group. The Sham group represents the control group with cecal ligation without puncture: that is, the cecum of the mouse is ligated by laparotomy, and the cecum is put back into the mouse body. The control group mice. MIC represents the experimental group treated with MIC: that is, the experimental group treated by injecting MIC into the tail vein of the CLP group mice.

[0019] Figure 1 The crystal structure ball-and-stick diagram of the MIC sample, its chemical formula is H 12 [Fe 28 (μ3-O)8(L-(+)-tart) 16 (CH3COO) 16 (H2O)8], the crystal system is orthorhombic, the space group is P21212, the unit cell parameters are α = 90°, β = 90°, γ = 90°, and Z = 2. The maximum width of the MIC molecule The maximum height is This indicates that MIC is a nano-sized molecular compound.

[0020] Figure 2 The main peaks of the simulated XRD curves of the MIC data correspond to those of the experimental test, indicating that the sample has a good purity (100%).

[0021] Figure 3 This is the infrared IR spectrum of the MIC sample. In the figure, 3420 cm -1 The peak at 1660cm belongs to the stretching mode of surface water molecules; -1 The peak at 1560cm is attributed to the bending vibration of water; -1 The peak at 1400cm belongs to the stretching vibration of C=O; -1 、1040cm -1 and 982cm -1 The peak at 900 cm belongs to the bending vibration of CO; -1 ~500cm -1 The infrared bands at belong to the bending and stretching vibrations of Fe-OH in MIC. These indicate that the structure of the sample is Figure 1 The crystal structure shown and Figure 2 The XRD results showed that the synthesized MIC had a good purity (100%).

[0022] Figure 4 The IL-6 level of the experimental group treated with MIC was significantly lower than that of the CLP group and close to that of the Sham group; the IL-4 level of the experimental group treated with MIC was significantly higher than that of the CLP group; thus indicating that MIC can be used to inhibit inflammation in septic mice. DETAILED DESCRIPTION

[0023] The present invention is further described in conjunction with the embodiments and drawings. However, the protection scope of the present invention includes but is not limited to the following embodiments. Changes and adjustments made without departing from the spirit and scope of the present invention shall also be included in the protection scope of the present invention.

[0024] The present invention is described below with reference to specific examples. The process condition values ​​in the following examples are exemplary, and the possible value ranges are as shown in the above invention content. For process parameters not specifically noted, conventional techniques can be used.

[0025] Example 1

[0026] Preparation of nano-sized iron-oxygen cluster drug molecules:

[0027] (1) In 30 mL of magnesium acetate-acetic acid buffer solution, 1.62 g (4 mmol) of ferric nitrate, 0.36 g (2.4 mmol) of L-(+)-tartaric acid and 0.19 g (0.40 mmol) of gadolinium nitrate were added in sequence, and after stirring, 0.182 g (0.40 mmol) of lanthanum carbonate was added to the solution to obtain a mixed solution, wherein the molar ratio of ferric nitrate, L-(+)-tartaric acid, gadolinium nitrate and lanthanum carbonate was 10:6:1:1, and the concentration of ferric nitrate in the magnesium acetate-acetic acid buffer solution was 0.1 mol / L;

[0028] (2) heating the mixed solution obtained in step (1) in a water bath at 95° C. for 3 hours, filtering the mixed solution after it cools to room temperature, and evaporating and culturing it at 25° C. for 18 days to obtain red blocky iron-oxygen cluster drug molecular crystals;

[0029] (3) drying the iron-oxygen cluster drug molecules obtained in step (2) under vacuum at 60° C. to obtain about 1.08 g of the nanosized iron-oxygen cluster drug molecules (MIC);

[0030] (4) The nano-sized iron-oxygen cluster compound (MIC) obtained after drying in step (3) was dissolved in sterile saline to a concentration of 200 μg / mL, and 100 μL was injected into the sepsis model mice in the CLP group through the tail vein, once every 24 hours, for a total of 2 injections. The changes in IL-4 and IL-6 in the diseased mice were observed.

Claims

1. A method for preparing a nano-sized iron-oxygen cluster drug molecule, the steps of which are as follows: (1) Adding ferric nitrate, L-(+)-tartaric acid and gadolinium nitrate in a magnesium acetate-acetic acid buffer solution in sequence, stirring evenly, and then adding carbonate to obtain a mixed solution, wherein: The molar ratio of ferric nitrate, L-(+)-tartaric acid, gadolinium nitrate and carbonate is 10:6:1:1, and the concentration of ferric nitrate in magnesium acetate-acetic acid buffer solution is 0.05-0.2 mol / L; (2) heating the mixed solution obtained in step (1) in a water bath at 90 to 98° C. for 2 to 4 hours, filtering the mixed solution after it cools to room temperature, and evaporating and culturing the obtained filtrate at room temperature for 2 to 3 weeks to obtain an iron-oxygen cluster drug molecule in the form of a red block or red powder; (3) The iron-oxygen cluster drug molecules obtained in step (2) are vacuum dried at 50-70° C. to obtain nano-sized iron-oxygen cluster drug molecules.

2. The method for preparing a nano-sized iron-oxygen cluster drug molecule according to claim 1, characterized in that: The carbonate is one of lanthanum carbonate, neodymium carbonate, cerium carbonate and gadolinium carbonate.

3. A nano-sized iron-oxygen cluster drug molecule, characterized in that: The method is prepared by the method of claim 1 or 2.

4. Use of the nano-sized iron-oxygen cluster drug molecule according to claim 3 in the preparation of a drug for treating sepsis.

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