Berberine carbon nanodot as well as preparation method and application thereof

Abstract

The invention discloses berberine carbon nanodots as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The preparation method comprises the following steps: carrying out a hydrothermal reaction on a berberine aqueous solution, filtering, centrifuging and collecting the solution. The berberine is used as a unique carbon source, the high-fluorescence carbon nanodot is synthesized through a hydrothermal method, the method is simple, low in cost, safe and green, other chemical reagents do not need to be added, potential toxicity caused by other chemical substances is avoided, and the berberine carbon nanodot obtained through synthesis is small in size, has good water solubility, can penetrate through a cell membrane and can be used for preparing the high-fluorescence carbon nanodot. The compound provided by the invention is simple in preparation process and easy for intestinal tissue cell uptake, can significantly alleviate intestinal epithelial cell death and intestinal epithelial cell barrier permeability abnormity caused by LPS (lipopolysaccharide) by alleviating intestinal tissue pathological injury, inflammatory response and tight junction protein loss of sepsis mice, and is effectively applied to treatment of intestinal barrier injury caused by sepsis.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to berberine carbon nanodots and a preparation method and application thereof. Background Art

[0002] Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Worldwide, the high morbidity and mortality of sepsis make it the leading cause of death in critically ill patients. The intestine is an effective barrier to prevent intestinal microorganisms and toxins from invading the body, and damage to the intestinal barrier is the initiating factor for death in patients with sepsis. At present, no effective drugs have been successfully developed to treat intestinal barrier damage in sepsis. Exploring the mechanism of intestinal barrier damage in sepsis and effective prevention and treatment strategies are issues that need to be urgently addressed in clinical practice.

[0003] As a traditional top-grade Chinese medicinal material, Coptis chinensis was first recorded in Shennong's Herbal Classic and has been used in my country for thousands of years. Berberine, a monomer substance of Chinese medicine and the main active ingredient of Coptis chinensis, has biological effects such as anti-inflammatory, antioxidant, and anti-apoptosis, but its wide application is limited by many factors such as limited administration routes and molecular weight that is difficult to pass through the biological membrane barrier. Carbon nanodots are a new type of zero-dimensional photoluminescent nanomaterial with advantages such as adjustable fluorescence emission wavelength, good photostability, water solubility, biocompatibility, and low biological toxicity. They have broad application prospects in biomedical treatment, photocatalysis, chemical sensing, etc., but the application of carbon nanodots in the treatment of sepsis intestinal barrier damage has not been reported. How to prepare a carbon nanodot Chinese medicine nanomaterial drug that has a good therapeutic effect on sepsis intestinal barrier damage, can be injected intravenously, and has no toxic side effects is one of the problems that need to be solved in the treatment of sepsis intestinal barrier damage. Summary of the invention

[0004] In order to solve the above technical problems, the purpose of the present invention is to provide a berberine carbon nanodots and a preparation method and application thereof, so as to solve the problems of the existing lack of effective drugs for treating intestinal barrier damage caused by sepsis, and the poor treatment effect of berberine on intestinal damage caused by sepsis due to factors such as its own limited administration route and difficulty in passing through biological membranes.

[0005] The technical solution of the present invention to solve the above technical problems is as follows:

[0006] A method for preparing berberine carbon nanodots comprises the following steps:

[0007] The berberine aqueous solution is subjected to hydrothermal reaction, filtered, and the solution is collected by centrifugation to obtain the product.

[0008] The beneficial effects of the present invention are as follows: the present invention uses berberine as the sole carbon source and synthesizes highly fluorescent carbon nanodots by a hydrothermal method. The method is simple, low-cost, safe and green, does not require the addition of other chemical reagents, and avoids the potential toxicity caused by other chemical substances. The berberine carbon nanodots obtained by synthesis are small in size, have good water solubility, can pass through cell membranes, are easily taken up by intestinal tissue cells, and can be effectively used in the treatment of intestinal barrier damage caused by sepsis.

[0009] Furthermore, the concentration of the berberine aqueous solution is 0.5-2 mg / mL.

[0010] Preferably, the concentration of the berberine aqueous solution is 1 mg / mL.

[0011] Furthermore, the temperature of the hydrothermal reaction is 200-250° C., and the time is 5-10 h.

[0012] Preferably, the temperature of the hydrothermal reaction is 220° C. and the time is 8 h.

[0013] Furthermore, the filtration uses a PESM membrane with a pore size of 0.20-0.25 μm.

[0014] Preferably, the filtration uses a PESM membrane with a pore size of 0.22 μm.

[0015] Furthermore, during the centrifugation process, the temperature is 3-5°C, the rotation speed is 4000-6000 rpm, and the time is 4-6 min.

[0016] Preferably, the temperature during the centrifugation process is 4°C, the rotation speed is 5000 rpm, and the time is 5 min.

[0017] A berberine carbon nanodot is prepared by adopting the preparation method.

[0018] The use of the above-mentioned berberine carbon nanodots in the preparation of drugs for treating intestinal barrier damage caused by sepsis.

[0019] The beneficial effects of the present invention are as follows: the berberine carbon nanodots prepared by the present invention can effectively improve the survival rate of septic mice, significantly reduce intestinal tissue pathological damage, inflammatory response and tight junction protein loss in septic mice, and can significantly reduce intestinal epithelial cell death and abnormal intestinal epithelial cell barrier permeability caused by LPS, thereby effectively treating sepsis intestinal barrier damage, and the berberine carbon nanodots have no significant impact or damage to multiple organs of mice, have no inhibitory effect on the proliferation activity of intestinal epithelial cells, and have almost no biological toxicity.

[0020] A drug for treating intestinal barrier damage caused by sepsis, wherein the active ingredient comprises the berberine carbon nanodots.

[0021] Furthermore, the drug is a berberine carbon nanodot aqueous solution.

[0022] Furthermore, the concentration of the berberine carbon nanodots aqueous solution is 1-10 mg / mL.

[0023] Preferably, the concentration of the berberine carbon nanodots aqueous solution is 5 mg / mL.

[0024] The present invention has the following beneficial effects:

[0025] (1) The present invention uses berberine as the sole carbon source and establishes a simple, low-cost, safe and green hydrothermal method for synthesizing highly fluorescent carbon nanodots. This method does not require the addition of other chemical reagents, thus avoiding the potential toxicity caused by other chemical substances during the synthesis process.

[0026] (2) The berberine carbon nanodots prepared by the present invention have a size in the range of 1-5 nm and have good water solubility. They can better penetrate the cell membrane and are easily taken up by intestinal tissue cells, thus solving the problem that when the diameter of the carbon nanodots is greater than 100 nm, monocytes and macrophages have a higher probability of recognizing and removing the carbon nanodots, and the problem that the body's cells have a low uptake rate of molecular Chinese medicine monomers.

[0027] (3) The berberine carbon nanodots prepared by the present invention can effectively improve the survival rate of septic mice, significantly reduce intestinal tissue pathological damage, inflammatory response and tight junction protein loss in septic mice, and significantly reduce LPS-induced intestinal epithelial cell death and intestinal epithelial cell barrier permeability abnormalities, indicating that berberine carbon nanodots have a specific and definite protective effect on intestinal barrier damage caused by sepsis, providing a good theoretical basis for its use in the treatment of sepsis-induced intestinal barrier damage.

[0028] (4) The berberine carbon nanodots prepared by the present invention have no significant effect on the liver and kidney functions of mice, have no damaging effect on multiple important organs of mice, and have no inhibitory effect on the proliferation activity of intestinal epithelial cells, indicating that the berberine carbon nanodots have almost no biological toxicity, providing strong evidence for their safe application. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 TEM image of berberine carbon nanodots in Experimental Example 1;

[0030] Figure 2 PL spectrum of berberine carbon nanodots in Experimental Example 1;

[0031] Figure 3 This is the Fourier transform infrared spectrum of berberine carbon nanodots in Experimental Example 1;

[0032] Figure 4This is a graph comparing the 7-day survival results of the four groups of mice in Experiment 2. Compared with the sham group, * P<0.05; compared with CLP, # P<0.05; compared with the BBR group, & P < 0.05;

[0033] Figure 5 The figure is a comparison of the HE staining and pathological scores of the intestinal tissues of the four groups of mice in Experimental Example 2. Compared with the sham group, * P<0.05; compared with CLP, # P<0.05; compared with the BBR group, & P < 0.05;

[0034] Figure 6 This is a comparison of the levels of inflammatory factors in the intestinal tissues of the four groups of mice in Experimental Example 2. Compared with the sham group, * P<0.05; compared with CLP, # P<0.05; compared with the BBR group, & P < 0.05;

[0035] Figure 7 This is a comparison result of the expression levels of tight junction protein ZO-1 and occludin protein in the intestinal tissue of four groups of mice in Experimental Example 2;

[0036] Figure 8 The figure is a comparison result of the LDH release rate levels of four groups of Caco2 cells in Experimental Example 3, wherein, compared with the control group, * P<0.05; compared with LPS, # P<0.05; compared with the BBR group, & P < 0.05;

[0037] Fig. 9 This is a comparison result of the TER levels of the four groups of Caco2 cells in Experimental Example 3, where compared with the control group, * P<0.05; compared with LPS, # P<0.05; compared with the BBR group, & P < 0.05;

[0038] Fig.10 This is a graph showing the comparison of liver and kidney function levels of mice in the NS group and the CDs group in Experimental Example 4;

[0039] Fig.11 This is a graph showing the comparison of pathological injury levels of myocardium, liver, spleen, lung, kidney, brain, and testis tissues between the NS group and the CDs group in Experimental Example 4;

[0040] Fig.12 This is a graph comparing the proliferation activity of Caco2 cells between the PBS group and the CDs group in Experimental Example 4. DETAILED DESCRIPTION

[0041] The principles and features of the present invention are described below in conjunction with the accompanying drawings. The examples are only used to explain the present invention and are not used to limit the scope of the present invention. If specific conditions are not specified in the embodiments, they are carried out according to normal conditions or conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0042] Embodiment 1:

[0043] A method for preparing berberine carbon nanodots comprises the following steps:

[0044] (1) 10 mL of 1 mg / mL berberine aqueous solution was transferred into a 20 mL polytetrafluoroethylene-lined autoclave and subjected to hydrothermal reaction at 220 °C in an oven for 8 h;

[0045] (2) filtering the hydrothermal reaction product of step (1) using a PESM membrane with a pore size of 0.22 μm to remove impurities with larger particles in the solution;

[0046] (3) The filtrate was transferred to an activated ultrafiltration tube and centrifuged at 4°C (5000 rpm, 5 min). The brown-yellow liquid collected was the berberine carbon nanodot solution.

[0047] Embodiment 2:

[0048] A method for preparing berberine carbon nanodots comprises the following steps:

[0049] (1) 10 mL of 0.5 mg / mL berberine aqueous solution was transferred into a 20 mL polytetrafluoroethylene-lined autoclave and subjected to hydrothermal reaction at 200 °C in an oven for 8 h;

[0050] (2) filtering the hydrothermal reaction product of step (1) using a PESM membrane with a pore size of 0.22 μm to remove impurities with larger particles in the solution;

[0051] (3) The filtrate was transferred to an activated ultrafiltration tube and centrifuged at 4°C (5000 rpm, 5 min). The brown-yellow liquid collected was the berberine carbon nanodot solution.

[0052] Embodiment 3:

[0053] A method for preparing berberine carbon nanodots comprises the following steps:

[0054] (1) 10 mL of 2 mg / mL berberine aqueous solution was transferred into a 20 mL polytetrafluoroethylene-lined autoclave and subjected to hydrothermal reaction at 250 °C in an oven for 8 h;

[0055] (2) filtering the hydrothermal reaction product of step (1) using a PESM membrane with a pore size of 0.22 μm to remove impurities with larger particles in the solution;

[0056] (3) The filtrate was transferred to an activated ultrafiltration tube and centrifuged at 4°C (5000 rpm, 5 min). The brown-yellow liquid collected was the berberine carbon nanodot solution.

[0057] Experimental Example 1: Characterization of Berberine Carbon Nanodots

[0058] 1. Experimental Methods

[0059] (1) Using transmission electron microscopy (TEM) to detect the morphology of berberine carbon nanodots;

[0060] (2) Using a photoluminescence (PL) analyzer to detect the PL spectral characteristics of berberine carbon nanodots;

[0061] (3) Use a spectrometer to perform Fourier transform infrared spectroscopy testing to detect the functional group characterization on the surface of berberine carbon nanodots.

[0062] 2. Experimental Results

[0063] The experimental results are as follows Figure 1-Figure 3 shown.

[0064] Depend on Figure 1 It can be seen that the berberine carbon nanodots prepared using berberine as the carbon source have a diameter of 1-5 nm, a uniform particle size, and a high yield. Figure 2 It can be seen that the emission spectrum of berberine carbon nanodots is blue light, with a wide luminescence spectrum and strong luminescence intensity; Figure 3 It can be seen that the surface of berberine carbon nanodots has chemical groups such as CH, CN and C=C which are related to the anti-inflammatory effect of carbon nanodots.

[0065] Test Example 2: Animal Experiment

[0066] 1. Experimental Methods

[0067] (1) Establishment of a mouse sepsis barrier injury model

[0068] The model was constructed by cecal ligation and puncture (CLP). Adult male C57BL / 6J mice weighing 20-25g were anesthetized with 1% pentobarbital (50mg / kg). The abdominal cavity was cut open under sterile conditions, the cecum was gently pulled out, and the distal end was ligated 2cm away. A 20-gauge needle was used to penetrate and puncture between the ligature and the end, squeeze out a little feces, return the cecum to the abdominal cavity, suture the abdominal wall, and then subcutaneously inject 37℃ saline (5mL / 100g) for resuscitation.

[0069] (2) Experimental groups

[0070] 67 adult male C57BL / 6J mice, weighing 20-25 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. They were randomly divided into 4 groups.

[0071] 1) Sham operation group: only laparotomy was performed to separate the cecum but without ligation and perforation;

[0072] 2) CLP group: mouse sepsis barrier damage model group;

[0073] 3) Berberine (BBR) group: 1 h after CLP construction, 5 mg / mL berberine aqueous solution was injected via the tail vein, a total of 100 μL;

[0074] 4) Berberine carbon nanodots treatment (CDs) group: 1 h after the CLP construction was completed, 5 mg / mL berberine carbon nanodots aqueous solution prepared in Example 1 was injected via the tail vein, a total of 100 μL.

[0075] (3) Seven-day survival rate test

[0076] The survival of the mice was observed immediately, 1d, 2d, 3d, 4d, 5d, 6d and 7d after the model was established, and the changes in the survival rate level were measured.

[0077] (4) Intestinal histopathological morphology and scoring

[0078] 24 hours after modeling, the small intestinal tissues of mice were collected, and the pathological changes of intestinal tissues were determined by HE staining and Chiu's score was calculated.

[0079] (5) Expression of inflammatory factors in intestinal tissue

[0080] 24 hours after modeling, the small intestinal tissues of mice were collected, and the expression levels of TNF-α, IL-1β and IL-6 in the intestinal tissues were determined by ELISA (the above ELISA kits were purchased from Wuhan Sewell Biotechnology Co., Ltd.).

[0081] (6) Expression of tight junction proteins in intestinal tissue

[0082] 24 hours after modeling, the small intestinal tissues of mice were collected, and the protein expression levels of Z0-1 and occludin in the intestinal tissues were determined by Western blot.

[0083] (7) Statistical analysis: SPSS 22.0 statistical software was used for analysis. The measured data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among the groups. P < 0.05 was considered statistically significant.

[0084] 2. Experimental Results

[0085] (1) By Figure 4 It can be seen that berberine carbon nanodots can significantly improve the 7-day survival rate of mice with sepsis, and have significant advantages over berberine. Compared with the sham group, the 7-day survival rate of mice in the CLP group was significantly reduced (P < 0.05); compared with the CLP group, the 7-day survival rate of mice in the BBR group was significantly increased (P < 0.05); compared with the CLP group and the BBR group, the 7-day survival rate of mice in the CDs group was significantly increased (P < 0.05).

[0086] (2) By Figure 5 It can be seen that berberine carbon nanodots can improve the pathological damage of intestinal tissue in septic mice, and have significant advantages over berberine. Compared with the sham group, the intestinal tissue pathology score of mice in the CLP group was significantly increased (P < 0.05); compared with the CLP group, the intestinal tissue pathology score of mice in the BBR group was significantly reduced (P < 0.05); compared with the CLP group and the BBR group, the intestinal tissue pathology score of mice in the CDs group was significantly reduced (P < 0.05).

[0087] (3) By Figure 6 It can be seen that berberine carbon nanodots can improve the inflammatory response of intestinal tissue in septic mice, and have significant advantages over berberine. Compared with the sham group, the expression levels of TNF-α, IL-1β and IL-6 in the intestinal tissue of mice in the CLP group were significantly increased (P<0.05); compared with the CLP group, the expression levels of TNF-α, IL-1β and IL-6 in the intestinal tissue of mice in the BBR group were significantly decreased (P<0.05); compared with the CLP group and BBR group, the expression levels of TNF-α, IL-1β and IL-6 in the intestinal tissue of mice in the CDs group were significantly decreased (P<0.05).

[0088] (4) By Figure 7It can be seen that berberine carbon nanodots can improve the expression level of tight junction proteins in the intestinal tissue of septic mice, and have significant advantages over berberine. Compared with the sham group, the expression levels of ZO-1 and occludin in the intestinal tissue of mice in the CLP group were significantly decreased (P<0.05); compared with the CLP group, the expression levels of ZO-1 and occludin in the intestinal tissue of mice in the BBR group were significantly increased (P<0.05); compared with the CLP group and the BBR group, the expression levels of ZO-1 and occludin in the intestinal tissue of mice in the CDs group were significantly increased (P<0.05).

[0089] Experimental Example 3: Cell experiment

[0090] 1. Experimental Methods

[0091] (1) Establishment of an in vitro intestinal barrier injury model using human intestinal epithelial cell line Caco2

[0092] Well-differentiated Caco2 cells in the logarithmic phase were cultured at 1×10 8 / L density was inoculated in the tranwell chamber, 400μL per well, and 600μL culture medium was added to the basal side of the chamber. The culture medium was changed 24 hours after inoculation. The cell growth was observed regularly. After about 7 days of culture, the cells formed a complete and dense monolayer, indicating that the in vitro barrier model was formed. Subsequently, Caco2 cells were incubated with 100μg / mL lipopolysaccharide (LPS) for 24 hours, and the in vitro intestinal barrier model was established.

[0093] (2) Experimental groups

[0094] Human intestinal epithelial cell line Caco2 was purchased from the Cell Bank of Type Culture Collection Committee of Chinese Academy of Sciences and used after subculture. The cells were randomly divided into 4 groups.

[0095] 1) Control group: Caco2 cells cultured in normal culture medium;

[0096] 2) LPS group: LPS was added to the culture medium to a final concentration of 100 μg / mL;

[0097] 3) Berberine (BBR) group: LPS and berberine were added to the culture medium at the same time, so that the final concentration of LPS was 100 μg / mL and the final concentration of berberine was 100 μg / mL;

[0098] 4) Berberine carbon nanodots treatment (CDs) group: LPS and berberine carbon nanodots were added to the culture medium at the same time, so that the final concentration of LPS was 100 μg / mL, and the final concentration of berberine carbon nanodots was 100 μg / mL.

[0099] (3) LDH release rate

[0100] 24 hours after modeling, the LDH concentration in the cell culture medium was measured using an ELISA instrument, and the LDH release rate of Caco2 cells was calculated.

[0101] (4) Transepithelial electrical resistance (TER)

[0102] 24 hours after modeling, the TER level of the Caco2 cell monolayer model was measured using an EVOM2 cell resistance meter.

[0103] (5) Statistical analysis

[0104] SPSS 22.0 statistical software was used for analysis. The measurement data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among the groups. P < 0.05 was considered statistically significant.

[0105] 2. Experimental Results

[0106] (1) By Figure 8 It can be seen that berberine carbon nanodots can improve the LDH release rate of Caco2 cells induced by LPS, and have significant advantages over berberine. Compared with the control group, the LDH release rate of Caco2 cells in the LPS group was significantly increased (P < 0.05); compared with the LPS group, the LDH release rate of Caco2 cells in the BBR group was significantly decreased (P < 0.05); compared with the LPS group and the BBR group, the LDH release rate of Caco2 cells in the CDs group was significantly decreased (P < 0.05).

[0107] (2) By Fig. 9 It can be seen that berberine carbon nanodots can improve the TER level of Caco2 cell barrier caused by LPS, and have significant advantages over berberine. Compared with the control group, the TER level of Caco2 cell barrier in the LPS group was significantly reduced (P < 0.05); compared with the LPS group, the TER level of Caco2 cell barrier in the BBR group was significantly increased (P < 0.05); compared with the LPS group and the BBR group, the TER level of Caco2 cell barrier in the CDs group was significantly increased (P < 0.05).

[0108] Test Example 4: Biological Toxicity Test

[0109] 1. Experimental Methods

[0110] (I) Animal experiments verify the biological toxicity of berberine carbon nanodots

[0111] (1) Experimental groups

[0112] Twenty adult male C57BL / 6J mice, weighing 20-25 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. They were divided into two groups using a random number table method.

[0113] 1) Normal saline control (NS) group: 100 μL of normal saline was injected via the tail vein;

[0114] 2) Berberine carbon nanodots administration (CDs) group: 5 mg / mL berberine carbon nanodots aqueous solution was injected via the tail vein, a total of 100 μL.

[0115] (2) Detection of liver function level in mice

[0116] 24 hours after the injection, peripheral venous blood was collected from the mice, and the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined by ELISA.

[0117] (3) Mouse renal function test

[0118] 24 hours after the injection, peripheral venous blood was collected from mice, and the levels of serum creatinine (Cr) and urea (BUN) were determined by ELISA.

[0119] (4) Evaluation of multi-organ pathology in mice

[0120] 24 hours after the injection, the myocardium, liver, spleen, lung, kidney, brain and testis of the mice were collected, and the pathological toxic effects of berberine carbon nanodots on the above organs of the mice were evaluated by HE staining.

[0121] (II) Cell experiment verifies the biological toxicity of berberine carbon nanodots

[0122] (1) Experimental groups

[0123] Human intestinal epithelial cell line Caco2 was purchased from the Cell Bank of Type Culture Collection Committee of Chinese Academy of Sciences and used after subculture. The cells were divided into two groups using random number table method.

[0124] 1) PBS control (PBS) group: PBS was added to the cell culture medium;

[0125] 2) Berberine carbon nanodots stimulation (CDs) group: Berberine carbon nanodots were added to the cell culture medium to a concentration of 100 μg / mL in the culture medium.

[0126] (2) Cell proliferation activity detection

[0127] After 24 h of treatment with berberine carbon nanodots, the CCK-8 kit (Wuhan Sewell Biotechnology Co., Ltd.) was used to detect the changes in the proliferation activity of Caco2 cells.

[0128] 3. Statistical analysis

[0129] SPSS 22.0 statistical software was used for analysis. The measurement data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among the groups. P < 0.05 was considered statistically significant.

[0130] 2. Experimental Results

[0131] (1) By Fig.10 It can be seen that intravenous injection of berberine carbon nanodots had no significant effect on the liver and kidney function of mice. There was no statistically significant difference in the levels of serum AST, ALT, Cr and BUN between the NS group and the CDs group (P>0.05).

[0132] (2) By Fig.11 It can be seen that intravenous injection of berberine carbon nanodots had no obvious damage to the important organs of mice. There was no significant difference in the pathological scores of myocardium, liver, spleen, lung, kidney, brain and testis tissues between the NS group and the CDs group (P>0.05).

[0133] (3) By Fig.12 It can be seen that berberine carbon nanodots have no obvious cytotoxic effect on Caco2 cells. There was no significant difference in the proliferation activity of Caco2 cells between the PBS group and the CDs group (P>0.05).

[0134] 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 method for preparing berberine carbon nanodots, It is characterized in that The following steps are involved: The berberine aqueous solution is subjected to hydrothermal reaction, filtered, and the solution is collected by centrifugation to obtain the product.

2. The method for preparing berberine carbon nanodots according to claim 1, It is characterized in that The concentration of the berberine aqueous solution is 0.5-2 mg / mL.

3. The method for preparing berberine carbon nanodots according to claim 1, It is characterized in that The temperature of the hydrothermal reaction is 200-250° C. and the time is 5-10 hours.

4. The method for preparing berberine carbon nanodots according to claim 1, It is characterized in that The filtration uses a PESM membrane with a pore size of 0.20-0.25 μm.

5. The method for preparing berberine carbon nanodots according to claim 1, It is characterized in that During the centrifugation process, the temperature is 3-5°C, the rotation speed is 4000-6000rpm, and the time is 4-6min.

6. A berberine carbon nanodot, It is characterized in that The method is prepared by the preparation method according to any one of claims 1 to 5.

7. Use of the berberine carbon nanodots according to claim 6 in the preparation of a drug for treating intestinal barrier damage caused by sepsis.

8. A drug for treating intestinal barrier damage in sepsis, It is characterized in that The active ingredient includes the berberine carbon nanodots as described in claim 6.

9. The drug for treating intestinal barrier damage in sepsis according to claim 8, It is characterized in that The drug is a berberine carbon nanodot aqueous solution.

10. The drug for treating intestinal barrier damage caused by sepsis according to claim 9, It is characterized in that The concentration of the berberine carbon nanodots aqueous solution is 1-10 mg / mL.

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