Cinnamaldehyde / polygonatum sibiricum polysaccharide-pickering emulsion and application thereof

Abstract

The application belongs to the field of antitumor compounds and specifically relates to a cinnamyl aldehyde / polysaccharide of rhizoma polygonati-Pickering emulsion, which comprises the following raw materials in the following amounts: cinnamyl aldehyde, olive oil, polysaccharide of rhizoma polygonati and zein; the preparation method of the cinnamyl aldehyde / polysaccharide of rhizoma polygonati-Pickering emulsion comprises the following steps: S1: dissolving cinnamyl aldehyde in olive oil as an oil phase and dissolving polysaccharide of rhizoma polygonati in zein as an aqueous phase; S2: mixing the aqueous phase and the oil phase and performing ultrasonic treatment on the mixed solution to obtain the cinnamyl aldehyde / polysaccharide of rhizoma polygonati-Pickering emulsion. The application also discloses the application of the cinnamyl aldehyde / polysaccharide of rhizoma polygonati-Pickering emulsion in the preparation of antitumor drugs. The application can solve the problems of poor solubility, poor stability and difficulty in drug preparation of cinnamyl aldehyde in the prior art, can significantly improve the solubility of cinnamyl aldehyde and the stability of cinnamyl aldehyde in the gastrointestinal tract, has a good antitumor effect and has a sensitization and synergistic effect on chemotherapy.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of anti-tumor compounds, in particular to a cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion and its application. BACKGROUND

[0002] Cinnamaldehyde is the main active ingredient of Guangxi Gui Shiwei traditional Chinese medicine Cinnamomum cassia, which can inhibit the growth of various tumor cells including colorectal cancer cells. However, as an aldehyde organic compound, cinnamaldehyde is a yellow viscous volatile oil with very low solubility in water, only 1.42 mg / mL, so it has poor oral bioavailability and is difficult to be made into a medicine. The aldehyde group structure in cinnamaldehyde leads to poor stability and easy oxidation, which is also the reason for the difficulty in the application of cinnamaldehyde.

[0003] In the prior art, it is prepared into a prodrug micelle, a gel, a nanoemulsion and the like to improve its solubility. However, the drug loading capacity of the prodrug micelle is limited, and a large amount of surfactant is usually added for solubilization in the nanoemulsion, but the use of a large amount of surfactant will destroy the tight junction of the digestive tract and destroy the intestinal flora, which is not conducive to the treatment of digestive tract tumors. SUMMARY

[0004] The purpose of the present application is to provide a cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion and its application to solve the technical problems raised in the background.

[0005] In order to achieve the above-mentioned purpose, the following technical solutions are adopted in the present application:

[0006] A cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion, comprising the following amount of raw materials: cinnamaldehyde 0.1-0.48 g, olive oil 0.605-1.5 mL, polygonatum sibiricum polysaccharide 0.1-0.6 g, and corn alcohol soluble protein 3-9 mL.

[0007] The preparation method of the cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion comprises the following steps:

[0008] S1: dissolving cinnamaldehyde in olive oil as an oil phase, and dissolving polygonatum sibiricum polysaccharide in corn alcohol soluble protein as an aqueous phase;

[0009] S2: mixing the aqueous phase and the oil phase, and ultrasonically treating the mixture to obtain a cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion.

[0010] Further, in S2, the aqueous phase and the oil phase are mixed in a volume ratio of (3:1)-(9:1).

[0011] Further, in S2, the ultrasonic treatment has a power of 200-500 W and a time of 7-15 min.

[0012] Use of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion in the preparation of an antitumor drug.

[0013] Further, the use of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion and a chemotherapeutic drug in the preparation of a combined antitumor drug.

[0014] The present application has the following beneficial effects compared with the prior art:

[0015] 1. The present application can significantly improve the solubility of cinnamyl aldehyde by preparing cinnamyl aldehyde into a high drug loading cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion without surfactants, and is stable in the gastrointestinal tract and easy to be taken orally.

[0016] 2. The present application has good antitumor effect, and can produce sensitization and synergistic effect on chemotherapy. At the same time, by using polysaccharide with intestinal protection effect as stabilizer, the intestinal tight junction and flora disorder destroyed by chemotherapy can be improved. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 is the preparation process diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application;

[0018] Figure 2 is the product schematic diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application;

[0019] Figure 3 is the preparation principle diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application;

[0020] Figure 4 is the structure diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application;

[0021] Figure 5 is the particle size distribution diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application;

[0022] Figure 6 is the electron microscope diagram of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion of the present application; wherein, A is a bright field observation diagram, B is a Nile red oil staining fluorescence observation diagram, and C is a transmission electron microscope observation diagram;

[0023] Figure 7is a scratch test diagram of the in-vitro tumor cell killing ability of the cinnamyl aldehyde / pachymaran-Pickering emulsion of the present application; wherein, A is a diagram of the migration inhibition effect of the ½IC50 cinnamyl aldehyde / pachymaran-Pickering emulsion on MC38 colorectal cancer cells; B is a diagram of the migration inhibition effect of the ½IC50 cinnamyl aldehyde / pachymaran-Pickering emulsion on LoVo colorectal cancer cells;

[0024] Figure 8 is a column chart of the in-vitro tumor cell invasion and migration inhibition ability of the cinnamyl aldehyde / pachymaran-Pickering emulsion of the present application; wherein, A is a column chart of the migration inhibition area percentage of the cinnamyl aldehyde / pachymaran-Pickering emulsion on MC38 colorectal cancer cells; B is a column chart of the migration inhibition area percentage of the cinnamyl aldehyde / pachymaran-Pickering emulsion on LoVo colorectal cancer cells;

[0025] Figure 9 is a live and dead cell staining diagram of the IC50 cinnamyl aldehyde / pachymaran-Pickering emulsion after acting on HCT-116 cells of the present application; wherein, A is a live cell staining diagram; B is a dead cell staining diagram; C is a live and dead cell staining diagram;

[0026] Figure 10 is a MC38 colorectal cancer modeling and administration process diagram of the present application;

[0027] Figure 11 is a single tumor volume growth change curve diagram of each group of animals of the present application;

[0028] Figure 12 is a mean tumor volume growth change curve diagram of each group of animals of the present application;

[0029] Figure 13 is a column chart of the tumor inhibition rate of each group on the 16th day of the experiment of the present application;

[0030] Figure 14 is a tumor volume and weight diagram of each group of animals of the present application; wherein A is a tumor volume diagram of each group of animals; B is a tumor weight column chart of each group of animals;

[0031] Figure 15 is a body weight change curve diagram of each group of animals during the administration process of the present application;

[0032] Figure 16 is a spleen weight column chart of each group of animals at the end of the experiment of the present application;

[0033] Figure 17 is a heart and liver weight diagram of each group of animals of the present application; wherein, A is a heart weight column chart, B is a liver weight column chart;

[0034] Figure 18 Fig. 8 is a kidney, lung weight diagram of each group of animals of the present application; wherein A is a kidney weight column chart; B is a lung weight column chart;

[0035] Figure 19 Fig. 9 is a liver function index diagram of each group of animals at the end of the experiment of the present application; wherein A is an ALT index column chart of liver function; B is an AST index column chart of liver function;

[0036] Figure 20 Fig. 10 is a kidney function index diagram of each group of animals at the end of the experiment of the present application; wherein A is a BUN index column chart of kidney function; B is a Crea index column chart of kidney function;

[0037] Figure 21 Fig. 11 is a colon AB-PAS staining diagram of each group of animals of the present application (scale = 100 μm);

[0038] Figure 22 Fig. 12 is a column chart of the number of goblet cells in the colon of each group of animals of the present application, n = 3;

[0039] Figure 23 Fig. 13 is a ZO-1 (red) and DAPI (blue) immunofluorescence staining section diagram of each group of animals of the present application (scale = 100 μm); wherein A is a ZO-1 (red) immunofluorescence staining section diagram; B is a DAPI (blue) immunofluorescence staining section diagram;

[0040] Figure 24 Fig. 14 is an immunofluorescence quantification column chart of each group of animals of the present application, n = 3;

[0041] Figure 25 Fig. 15 is a CRC mouse intestinal junction protein mRNA level column chart of each group of animals of the present application, n = 6; *: P < 0.05; **: P < 0.01; ***: P < 0.001; wherein A is a RNA relative expression amount column chart of intestinal goblet cell secretion Muc 2; B is a RNA relative expression amount column chart of intestinal TJ protein; C is a RNA relative expression amount column chart of intestinal AJ protein;

[0042] Figure 26 Fig. 16 is a cinnamon aldehyde / polygonatum polysaccharide-Pickering intestinal flora alpha-diversity analysis diagram of the present application; wherein A is an ACE index analysis diagram; B is a Chao index analysis diagram; C is a Shannon index analysis diagram; D is a Simpson index analysis diagram;

[0043] Figure 27 Fig. 17 is a Bray-Curtis dissimilarity (PCoA) based beta-diversity analysis diagram of the present application;

[0044] Figure 28This is a diagram showing the relative abundance of gut microbiota at the phylum level in this invention;

[0045] Figure 29 This is a phylum-level dominant bacterial community diagram of the present invention. *: P < 0.05; **: P < 0.01; ***: P < 0.001; where A is a bar chart of relative abundance of Bacteroidetes; B is a bar chart of relative abundance of Verrucous Microbes; C is a bar chart of relative abundance of Bacillus; and D is a bar chart of relative abundance of Fermentobacteria. Detailed Implementation

[0046] 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 preferred embodiments. However, it should be noted that many details listed in the specification are merely to provide the reader with a thorough understanding of one or more aspects of the invention, and these aspects of the invention can be achieved even without these specific details.

[0047] A cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion comprises the following raw materials: cinnamaldehyde 0.1-0.48g, solvent olive oil 0.605-1.5mL, stabilizer Polygonatum polysaccharide 0.1-0.6g, and emulsifier zein 3-9mL.

[0048] like Figure 1 As shown, the preparation method of the cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion includes the following steps:

[0049] S1: Cinnamaldehyde was dissolved in olive oil as the oil phase, and Polygonatum polysaccharide was dissolved in 1.5% zein solution as the aqueous phase;

[0050] S2: Mix the aqueous phase and oil phase at a volume ratio of (3:1)-(9:1), and then sonicate the mixture at a power of 200-500W for 7-15 minutes to obtain a cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion, such as... Figure 2 As shown.

[0051] like Figure 3 As shown, this invention uses cinnamaldehyde as the main drug and zein as the emulsifier. By adding Polygonatum polysaccharide as a dispersant and stabilizer, and combining this with ultrasonic uniform dispersion, a stable oil-in-water cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion is finally obtained, the structure of which is shown below. Figure 4 As shown.

[0052] Example 1

[0053] A cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following raw material composition: cinnamaldehyde 0.395g, solvent olive oil 0.605mL, stabilizer polygonatum polysaccharide 0.2g, emulsifier zein 5mL.

[0054] The preparation method of the cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following steps:

[0055] S1: dissolve cinnamaldehyde in olive oil as oil phase, and dissolve polygonatum polysaccharide in 1.5% zein solution as water phase;

[0056] S2: mix the water phase and the oil phase in a volume ratio of 6:1, and ultrasonically treat the mixed solution, the ultrasonic treatment power is 250W, and the time is 7 minutes, to obtain the cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion.

[0057] Example 2

[0058] A cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following raw material composition: cinnamaldehyde 0.48g, solvent olive oil 1.5mL, stabilizer polygonatum polysaccharide 0.5g, emulsifier zein 5mL.

[0059] The preparation method of the cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following steps:

[0060] S1: dissolve cinnamaldehyde in olive oil as oil phase, and dissolve polygonatum polysaccharide in 1.5% zein solution as water phase;

[0061] S2: mix the water phase and the oil phase in a volume ratio of 5:1, and ultrasonically treat the mixed solution, the ultrasonic treatment power is 500W, and the time is 15 minutes, to obtain the cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion.

[0062] Example 3

[0063] A cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following raw material composition: cinnamaldehyde 0.4g, solvent olive oil 0.6mL, stabilizer polygonatum polysaccharide 0.6g, emulsifier zein 9mL.

[0064] The preparation method of the cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion, comprising the following steps:

[0065] S1: dissolve cinnamaldehyde in olive oil as oil phase, and dissolve polygonatum polysaccharide in 1.5% zein solution as water phase;

[0066] S2: the water phase and the oil phase are mixed in a volume ratio of 9:1, and the mixture is subjected to ultrasonic treatment at a power of 500 W for 10 minutes to obtain a cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion.

[0067] Example 4

[0068] A cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion, comprising the following raw material composition: cinnamaldehyde 0.1 g, solvent olive oil 0.9 mL, stabilizer polysaccharide from polygonatum 0.1 g, emulsifier zein 3 mL.

[0069] The preparation method of the cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion, comprising the following steps:

[0070] S1: dissolve cinnamaldehyde in olive oil as the oil phase, and dissolve polysaccharide from polygonatum in 1.5% zein solution as the water phase;

[0071] S2: the water phase and the oil phase are mixed in a volume ratio of 3:1, and the mixture is subjected to ultrasonic treatment at a power of 400 W for 10 minutes to obtain a cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion.

[0072] 1. Characterization of cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion

[0073] 1.1 The cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion prepared in examples 1-4 is detected for solubility under ultraviolet spectrophotometer at a wavelength of 286 nm, and the results are shown in Table 1;

[0074] Table 1 Solubility of cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion

[0075]

[0076] As can be seen from Table 1, compared with the solubility of cinnamaldehyde in water recorded in the chemical module database (pubchem) of 1.42 mg / mL, the solubility of the cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion prepared in examples 1-4 is significantly improved, among which example 2 reaches 79.1 mg / mL, but considering the solubility and stability, example 1 is more suitable for subsequent experiments, so example 1 is used as the experimental object for subsequent experiments.

[0077] 1.2 The particle size of the cinnamaldehyde / polysaccharide from polygonatum-Pickering emulsion obtained in example 1 is detected, and the results are shown in Figure 5

[0078] ​1.3 The cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion obtained in Example 1 was observed under a fluorescence microscope for its droplet structure, as shown in Figure 6 Figure 6 A is a bright field observation image, B is a Nile red oil staining fluorescence observation image, and C is a transmission electron microscope observation image.

[0079] As shown in Figure 5-6 , the particle size of the cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion was 872.7 ± 19.8 nm, and clear oil-in-water structure was observed under a transmission electron microscope, indicating that the emulsion of the application is a stable preparation, which can improve the stability of cinnamaldehyde and is conducive to its in vivo application.

[0080] 2. In vitro anti-colorectal cancer experiment

[0081] Cinnamaldehyde group (Cin), cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion group (Cin-Pickering), and blank model control group (control) were set up, and scratch experiments were performed on LoVo and MC38 cells, and the percentage of cell migration area was calculated, as shown in Figure 7-8

[0082] Live / dead cell staining experiments were performed on HCT-116 cells, as shown in Figure 9

[0083] As can be seen from Figure 7-9 , the killing ability of the Cin-Pickering group on HCT-116, LoVo, and MC38 cells was comparable to that of the Cin group, indicating that the cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion of the application has the ability to effectively inhibit the migration and invasion of various colorectal cancer cells.

[0084] 3. In vivo anti-colorectal cancer experiment

[0085] To investigate the efficacy of the cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion of the application in sensitizing colorectal cancer adjuvant chemotherapy drugs, MC38 colorectal cancer subcutaneous tumor models were constructed, 5 animals were grouped, and divided into saline group (saline), 5-fluorouracil (5-FU) + oxaliplatin (Oxa) drug chemotherapy group (5-FU + Oxa), cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion synergistic drug chemotherapy group (5-FU + Oxa + Cin-P), cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion group (Cin-P), and cinnamaldehyde group (Cin), as shown in Figure 10

[0086] After the experiment, the tumor volume of each group was measured, the average tumor volume of each group was calculated, and finally the tumor inhibition rate was calculated, as shown in​​​​Figure 11-13 At the end of the experiment, the tumors of each group were removed, measured and weighed, as shown in Table 2. Figure 14

[0087] As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect, Figure 11-13 As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect, Figure 13 As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect,

[0088] As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect, Figure 14 As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect,

[0089] As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect,

[0090] In addition, as can be seen from Table 3, the 5-FU+Oxa group significantly increased the growth rate of tumors after the third administration (day 11), indicating that it developed resistance to chemotherapy after multiple uses, but the 5-FU+Oxa+Cin-P group still significantly inhibited tumor growth at the same time, indicating that the cinnamaldehyde / polysaccharide from Polygonatum sibiricum - Pickering emulsion has the potential to be used as an auxiliary treatment synergistic drug, and can effectively inhibit the occurrence of drug resistance of chemotherapeutic drugs. Figure 11-12 4. Adverse reaction experiment

[0091] Based on the in vivo anti-colorectal cancer experiment of experiment 3, the body weight of the animals was monitored daily during the administration, as shown in Table 4, and the weight of the spleen and other organs of the animals was detected after the experiment, as shown in Table 5, and the liver function and kidney function of the animals were detected, as shown in Table 6.

[0092] Figure 15 Figure 16-18 Figure 19-20

[0093] As can be seen from Table 3, the 5-FU+Oxa+Cin-P group has the best anti-tumor effect, Figure 15 ​​​​​The results show that the body weight of the 5-FU+Oxa and 5-FU+Oxa+Cin-P groups, which received chemotherapy drugs, decreased significantly compared to the saline group. However, administration of the cinnamaldehyde raw material (Cin group) and the cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion (Cin-P group) did not cause a decrease in mouse body weight, indicating that they have tumor-suppressive effects comparable to chemotherapy drugs without causing a decrease in mouse body weight. Furthermore, the body weight of the 5-FU+Oxa+Cin-P and 5-FU+Oxa groups increased slightly in the later stages, suggesting that the 5-FU+Oxa+Cin-P group can reduce the adverse reaction of body weight loss caused by chemotherapy drugs.

[0094] During the experiment, the 5-FU+Oxa group caused diarrhea in animals after repeated administration, but the 5-FU+Oxa+Cin-P group did not show this adverse reaction, which may be related to the recovery of body weight.

[0095] from Figure 16-18 The results show that the 5-FU+Oxa group had no significant effect on the weight of the heart, liver, lungs, and kidneys, but a significant effect on the spleen weight. The spleen weight in the 5-FU+Oxa group was 0.0220±0.0023g, a significant decrease compared to the 0.0576±0.0158g in the saline group. Since the spleen is related to the body's systemic immune function, this indicates that chemotherapy caused severe immunosuppression. In contrast, the spleen weight in the 5-FU+Oxa+Cin-P group was 0.0318±0.0027g, a 0.45-fold increase compared to the 5-FU+Oxa group, indicating that it could reverse the immunosuppressive effects induced by chemotherapy.

[0096] from Figure 19-20 As can be seen, the 5-FU+Oxa group caused an increase in ALT, but the liver function of the 5-FU+Oxa+Cin-P group returned to normal.

[0097] The results above indicate that the combined use of chemotherapy drugs with cinnamaldehyde / Polygonatum polysaccharide-Pickering emulsion not only improves the efficacy of adjuvant chemotherapy but also enhances the safety of chemotherapy and reduces the occurrence of adverse reactions.

[0098] 5. Intestinal wall injury experiment

[0099] The changes and patterns of mouse goblet cells were studied using AB-PAS staining experiments, such as... Figure 21-25 As shown.

[0100] like Figure 21As shown, the content of goblet cells (purple particles) was rich and evenly distributed in the healthy group (Healthy). The number of goblet cells was significantly reduced in the model blank control group (Saline) and the chemotherapy group (5-Fu+Oxa) under naked eye. However, the loss of goblet cells caused by chemotherapy was reversed after the administration of cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion (Cin-P). As shown in Figure 22 As shown, the quantitative data of goblet cells further verified the results.

[0101] In order to directly observe the structural changes and expression of intestinal wall proteins, ZO-1 was used for intestinal immunofluorescence staining. As shown in Figure 23 and Figure 24 As shown, the expression of red fluorescence (ZO-1) on the outermost layer of the intestinal crypt was strong in the healthy group (Healthy), and the intestinal connection was complete. The expression intensity of fluorescence was reduced in the Saline group and the 5-Fu+Oxa group, and the connection of intestinal crypt was incomplete. After the administration of cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion (Cin-P), the expression of ZO-1 white was significantly increased. Therefore, cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion (Cin-P) can slow down the destruction of intestinal wall function in CRC chemotherapy mice.

[0102] As shown in Figure 25 The intestinal TJ protein (ZO-1) and AJ protein (E-cadherin) and the Muc 2 secreted by goblet cells were quantified at the transcription level (qPCR), and the results showed that the mRNA expression levels of ZO-1 and E-cadherin were significantly reduced in the model blank control group (Saline) and the chemotherapy group (5-Fu+Oxa). When cinnamaldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion (Cin-P) was administered, the mRNA expression content increased, and the reduction of intestinal connection protein caused by CRC chemotherapy was alleviated.

[0103] 6. Intestinal flora and metabolite experiment

[0104] The microbial diversity in the sample was studied by analyzing the alpha diversity through caecal content 16S rRNA sequencing. Chao and ACE represent the abundance of flora, and Shannon (Shannon index) and Simpson (Simpson index) are used to estimate the diversity of microorganisms in the sample. The larger the value, the higher the community diversity, and the results are shown in Figure 26-29

[0105] As shown in Figure 26 ​As shown, the results showed that the saline group and the mice receiving chemotherapy group had up-regulated bacterial abundance and diversity compared with the healthy group, and it was speculated that the proportion of harmful bacteria increased, while the cinnamaldehyde / pachyman Pickering emulsion adjusted the intestinal flora abundance and diversity of chemotherapy-induced CRC mice, making them tend to be healthy mice.

[0106] The structure of intestinal flora was analyzed by principal coordinate analysis (PCoA) of Bray-Curtis distance, as shown in FIG. 6. Figure 27-29 As shown, the principal coordinate analysis (PCoA) based on Bray-Curtis distance showed that compared with the model group (saline) and the chemotherapy group (5-Fu+Oxa), the cinnamaldehyde / pachyman Pickering emulsion (Cin-P) could significantly improve the structure of intestinal flora in the cecal contents of mice.

[0107] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. The use of a cinnamyl aldehyde / polygonatum polysaccharide-Pickering emulsion in the preparation of an antitumor drug, characterized in that, The cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion is composed of cinnamyl aldehyde 0.1-0.48 g, olive oil 0.605-1.5 mL, polygonatum sibiricum polysaccharide 0.1-0.6 g and zein 3-9 mL; The preparation method of the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion comprises the following steps: S1: dissolving cinnamyl aldehyde in olive oil as an oil phase and dissolving polygonatum sibiricum polysaccharide in zein as an aqueous phase; S2: mixing the aqueous phase and the oil phase and performing ultrasonic treatment on the mixed solution to obtain the cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion.

2. The cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion according to claim 1 for use in the preparation of an antitumor drug, characterized in that: In S2, the aqueous phase and the oil phase are mixed in a volume ratio of (3:1)-(9:1).

3. The cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion according to claim 1 for use in the preparation of an antitumor drug, characterized in that: In S2, the ultrasonic treatment is performed at a power of 200-500 W for 7-15 min.

4. The cinnamaldehyde / polygonatum polysaccharide-Pickering emulsion according to claim 1 for use in the preparation of an antitumor drug, characterized in that: The cinnamyl aldehyde / polygonatum sibiricum polysaccharide-Pickering emulsion and a chemotherapeutic drug are used in the preparation of a combined anti-tumor drug.

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