CN119386202A - Application of novel nanometer preparation containing zingiberenone A in preparation of antitumor drugs - Google Patents

Abstract

The present invention discloses an application of a novel nano preparation containing gingerolone A in the preparation of an anti-tumor drug, wherein the nano preparation comprises amino-modified dendritic mesoporous silica and gingerolone A loaded on the amino-modified dendritic mesoporous silica. The present invention adopts amino-modified dendritic mesoporous silica to load gingerolone A, and prepares a novel nano preparation containing gingerolone A with high drug loading, high encapsulation rate, and high biocompatibility. The preparation has low cytotoxicity, can be quickly taken up by tumor cells, significantly enhances the ability of gingerolone A to eliminate tumor cells, and effectively inhibits the proliferation of tumors in vivo. The therapeutic effect thereof is better than that of the commonly used clinical anti-tumor drug dabrafenib, and the preparation has broad application prospects.

Description

Application of novel nanometer preparation containing zingiberenone A in preparation of antitumor drugs

Technical Field

The invention relates to the technical field of medicines, in particular to application of a novel nano preparation containing zingibenone A in preparation of antitumor drugs.

Background

The existing tumor treatment method mainly adopts surgical excision, chemotherapy and radiotherapy, but has the limitations of strong toxic and side effects, easy recurrence and the like. Therefore, the screening of novel, safe and effective antitumor drugs has very important clinical significance.

Jiang Xitong A (Gingerenone A, GA) is a natural phytochemical substance extracted from rhizoma Zingiberis recens, and has wide medicinal value, including anti-tumor, antioxidant, antiaging, antiinflammatory, antiviral, and blood sugar control. Studies have shown that GA can promote anti-proliferation and aging (Gingerenone A Induces Antiproliferation and Senescence of Breast Cancer Cells.Antioxidants.;Tzu-Jung Yu.;et al.). of breast cancer cells induced by oxidative stress while GA selectively kills cancer cells (Identification of a Dual Inhibitor of Janus Kinase 2(JAK2)and p70 Ribosomal S6 Kinase1(S6K1)Pathways.;Sanguine Byun.;et al.), by dual inhibition of JAK2 and S6K1 is a potent anti-tumor active ingredient.

However, jiang Xitong a is poor in solubility, permeability, stability and absorbability, and therefore it is difficult to achieve an effective therapeutic concentration after use to achieve the desired effect, which greatly limits its range of application.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide an application of a novel nano preparation containing zingibenone A in preparing antitumor drugs, wherein the novel nano preparation which has high drug loading capacity, high encapsulation efficiency, high biocompatibility and Jiang Xitong A is prepared by adopting aminated dendritic mesoporous silica loaded Jiang Xitong A, the preparation has low cytotoxicity, can be rapidly taken up by tumor cells, remarkably enhances the capacity of eliminating tumor cells of Jiang Xitong A, effectively inhibits proliferation of tumors in vivo, has a treatment effect superior to that of clinical common antitumor drugs, namely Darafenib, and has a wide application prospect.

In order to achieve the above purpose, the technical scheme of the invention is as follows:

an application of a novel nano preparation containing gingerol A in preparing antitumor drugs, wherein the nano preparation comprises amino dendritic mesoporous silica and Jiang Xitong A loaded on the amino dendritic mesoporous silica.

Optionally, the tumor comprises one or more than two of melanoma, lymphohematopoietic tumor, endocrine tumor, lung and mediastinum tumor, breast tumor, digestive system tumor, urinary and male reproductive system tumor, female reproductive system tumor, head and neck tumor, central nervous system tumor, skin tumor, bone and soft tissue.

Optionally, the dosage form of the medicament comprises a tablet, a capsule, a pill, an injection, a sustained release preparation or a controlled release preparation.

Optionally, the administration route of the antitumor drug comprises one or more of intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration _、 rectal administration, skin mucosa administration and inhalation administration.

Optionally, the dosage of the nano preparation in the anti-tumor drug is 100 mg/kg-400 mg/kg.

Optionally, the anti-tumor drug is a drug for inhibiting tumor growth or inhibiting proliferation of tumor cells.

Optionally, the anti-tumor drug is a drug that promotes or induces apoptosis of tumor cells.

Optionally, the anti-tumor drug is a drug for inhibiting the growth of the transplanted tumor.

Optionally, the antitumor drug further comprises a pharmaceutically acceptable carrier, an excipient and/or an auxiliary material.

Optionally, the loading amount of Jiang Xitong a in the nano-preparation is 15% -30%.

Optionally, the encapsulation rate of Jiang Xitong a in the nano-preparation is 11% -35%.

Optionally, the particle size of the nano preparation is 50 nm-200 nm.

Optionally, the specific surface area of the nano-preparation is 800m ²/g～1000m²/g.

Optionally, the particle size of the amination dendritic mesoporous silica is 50 nm-200 nm.

Optionally, the aperture of the amination dendritic mesoporous silica is 2 nm-10 nm.

Optionally, the specific surface area of the aminated dendritic mesoporous silica is 300m ²/g～1000m²/g.

Optionally, the preparation method of the nano preparation comprises the following steps:

and dissolving Jiang Xitong A in a solvent to obtain Jiang Xitong A solution, adding the Jiang Xitong A solution and the aminated dendritic mesoporous silica into a buffer solution for reaction to load the gingerol A on the aminated dendritic mesoporous silica, and obtaining the nano preparation.

The mass ratio of Jiang Xitong A to the aminated dendritic mesoporous silica in the Jiang Xitong A solution is (1-5): 1.

The buffer solution comprises one or more than two of phosphate buffer solution, borate buffer solution, citrate buffer solution, phosphate and trimethylol methane, acetate buffer solution, imidazole salt buffer solution and carbonate buffer solution.

The pH of the buffer solution is 5.0-7.4.

The concentration of Jiang Xitong A in Jiang Xitong A solution is 2 mg/mL-6 mg/mL.

The solvent comprises any one of acetone, acetonitrile, ethanol, methanol and dimethyl sulfoxide.

The reaction temperature is 25-80 ℃, and the reaction time is 6-36 h.

The invention also discloses an anti-tumor drug, the effective component is a novel nano preparation containing the gingerol A, and the nano preparation is the nano preparation in the application.

The implementation of the embodiment of the invention has the following beneficial effects:

(1) The invention adopts the amination dendritic mesoporous silica to load Jiang Xitong A so as to prepare a novel nano preparation containing Jiang Xitong A, which has high drug loading, high encapsulation efficiency and high biocompatibility, has lower cytotoxicity, can be quickly taken up by tumor cells, obviously enhances the capability of Jiang Xitong A for eliminating tumor cells, effectively inhibits the proliferation of tumors in vivo, has a treatment effect superior to that of a clinical common antitumor drug Darafenib, can be applied to the aspect of anticancer drugs, and has wide application prospect.

(2) According to the invention, the amination modified dendritic mesoporous silica is selected as a drug carrier, jiang Xitong A is loaded on the drug carrier through non-covalent acting force, so that the nano preparation is highly enriched at a tumor part, the effect of targeting the tumor is achieved, and the bioavailability of Jiang Xitong A is improved.

(3) The experimental result shows that the nano preparation containing Jiang Xitong A can remarkably inhibit proliferation of A431 human epidermal cancer cells, A375 human malignant melanoma cells, caco2 human colon adenocarcinoma cells, SW579 human thyroid squamous carcinoma cells, HCT-116 human colorectal cancer cells and HepG2 human hepatoma cells, has wide anti-tumor effect, particularly remarkable effect on melanoma, shows good effect of inhibiting tumor growth on a mouse transplantation tumor model, has no obvious toxic or side effect, has good application prospect and higher application value in the aspect of preparing anticancer drugs, and has the advantages of simple preparation method, low cost and good economic benefit of the patent medicine.

Drawings

FIG. 1 is a graph showing the effect of GA@AMSN and GA at different concentrations on proliferation of A431 human epidermal carcinoma cells in example 2 of the present invention.

FIG. 2 is a graph showing the effect of GA@AMSN and GA at various concentrations on proliferation of A375 human malignant melanoma cells according to example 2 of the present invention.

FIG. 3 is a graph showing the effect of GA@AMSN and GA at various concentrations on proliferation of Caco2 human colon adenocarcinoma cells in example 2 of the present invention.

FIG. 4 is a graph showing the effect of GA@AMSN and GA at various concentrations on proliferation of SW579 human thyroid squamous carcinoma cells in example 2 of the present invention.

FIG. 5 is a graph showing the effect of GA@AMSN and GA at different concentrations on the proliferation of HCT-116 human colorectal cancer cells according to example 2 of the present invention.

FIG. 6 is a graph showing the effect of GA@AMSN and GA at different concentrations on proliferation of liver cancer cells of HepG2 human in example 2 of the present invention.

FIG. 7 shows the pharmacodynamic evaluation of the test drug of example 2 of the present invention on A375 cell mice subcutaneously transplanted tumor model (A, tumor growth curve; B, tumor weight; C, tumor picture).

FIG. 8 shows the pharmacodynamic evaluation of the test drug of example 2 of the present invention on a model of subcutaneous transplantation tumor in A375 cell mice (A, tumor-bearing mice weight change curve; B, tumor-bearing mice weight relative change curve).

FIG. 9 is a graph showing the H & E staining results of liver after treatment with the test drug (GA@AMSN) of example 2 of the present invention for days.

Detailed Description

The invention is further illustrated below in connection with specific examples, but is not limited in any way.

The invention discloses an application of a novel nano preparation containing zingibenone A in preparing antitumor drugs, wherein the nano preparation comprises amino dendritic mesoporous silica and Jiang Xitong A loaded on the amino dendritic mesoporous silica.

In a specific embodiment, the tumor comprises one or more of melanoma, lymphohematopoietic tumor, endocrine tumor, lung and mediastinal tumor, breast tumor, digestive system tumor, urinary and male reproductive system tumor, female reproductive system tumor, head and neck tumor, central nervous system tumor, skin tumor, and bone and soft tissue.

In a specific embodiment, the dosage form of the medicament comprises a tablet, capsule, pill, injection, sustained release formulation or controlled release formulation.

In a specific embodiment, the route of administration of the antitumor drug includes one or more of intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration _、 rectal administration, dermal mucosa administration and inhalation administration.

In a specific embodiment, the dosage of the nano-preparation in the anticancer drug is 100 mg/kg-400 mg/kg.

In one embodiment, the anti-neoplastic agent is an agent that inhibits tumor growth or inhibits proliferation of tumor cells.

In one embodiment, the anti-neoplastic agent is an agent that promotes or induces apoptosis in neoplastic cells.

In one embodiment, the anti-neoplastic agent is an agent that inhibits the growth of a transplanted tumor.

In a specific embodiment, the antitumor drug further comprises a pharmaceutically acceptable carrier, excipient and/or adjuvant.

In one embodiment, the loading of Jiang Xitong a in the nanofabricated is 15% -30%.

In one embodiment, the encapsulation efficiency of Jiang Xitong a in the nanofabricated is 11% -35%.

In one embodiment, the particle size of the nano-formulation is 50nm to 200nm.

In one embodiment, the specific surface area of the nano-formulation is 800m2/g to 1000m2/g.

In one embodiment, the particle size of the aminated dendritic mesoporous silica is 50nm to 200nm.

In one embodiment, the aminated dendritic mesoporous silica has a pore size of 2nm to 10nm.

In one embodiment, the specific surface area of the aminated dendritic mesoporous silica is 300m ²/g～1000m²/g.

In one embodiment, a method of preparing a nanofabricated formulation comprises:

(1) The template and catalyst are mixed in water to form an aqueous phase.

(2) The silicon source is mixed with a solvent to form an oil phase.

(3) And carrying out homogeneous phase reaction on the oil phase and the water phase, centrifuging and drying after the reaction is finished, and calcining to obtain the dendritic mesoporous silica.

(4) Adding dendritic mesoporous silica and an ammonia source into acetonitrile solution for amination modification to realize amination modification, so as to obtain the aminated dendritic mesoporous silica.

(5) And (3) dissolving Jiang Xitong A in a solvent to obtain Jiang Xitong A solution, adding Jiang Xitong A solution and the aminated dendritic mesoporous silica into a buffer solution for reaction to load Jiang Xitong A on the aminated dendritic mesoporous silica, and thus obtaining the nano preparation.

Specifically, the invention firstly prepares dendritic mesoporous silica with a unique central radial pore structure in a water/oil two-phase system, then modifies amino groups on the surface of the dendritic mesoporous silica, compared with the traditional mesoporous silica, the invention selects dendritic mesoporous silica with higher pore permeability and larger pore volume, various surface functions and good biocompatibility as a drug carrier, further carries out amino modification on the dendritic mesoporous silica, realizes high load on Jiang Xitong A by using the aminated dendritic mesoporous silica as the carrier through non-covalent acting force, and has the characteristics of uniform particle size, high drug loading, high encapsulation efficiency, high biocompatibility and low toxicity.

Furthermore, the preparation conditions are reasonably optimized to regulate and control the structure of the mesoporous silica nanomaterial, including the particle size, the pore size, the specific surface area and the like, so that the mesoporous structure with relatively good pore size distribution rate is formed.

In one embodiment, the mass ratio of Jiang Xitong A to the aminated dendritic mesoporous silica in Jiang Xitong A solution is (1-5): 1.

In a specific embodiment, the buffer solution comprises one or more of phosphate buffer, borate buffer, citrate buffer, phosphate and trimethylol methane, acetate buffer, imidazolium buffer, carbonate buffer.

In one embodiment, the pH of the buffer solution is 5.0 to 7.4.

In one embodiment, jiang Xitong A is present in the Jiang Xitong A solution at a concentration of 2mg/mL to 6mg/mL.

In a specific embodiment, the solvent in step (5) includes any one of acetone, acetonitrile, ethanol, methanol, dimethyl sulfoxide.

In one embodiment, the temperature of the homogeneous reaction is 25 ℃ to 80 ℃ and the time of the homogeneous reaction is 6 hours to 36 hours.

In a specific embodiment, the templating agent comprises one or two of cetyltrimethylammonium chloride, octadecyltrimethylammonium chloride, cetyltrimethylammonium bromide, cetyltrimethylammonium chloride, cetylpyridinium chloride, dodecyltrimethylammonium bromide. Preferably, the template is cetyltrimethylammonium chloride.

In a specific embodiment, the catalyst comprises one or more of triethanolamine, tripropanolamine, diethanolamine, ethanolamine and ammonia water. Preferably, the catalyst is triethanolamine.

In a specific embodiment, the silicon source comprises one or more of ethyl orthosilicate, methyl orthosilicate, tetra (2-methoxy-1-methylethyl) silicate, tetraisopropyl orthosilicate, tetrabutyl silicate, tetraisopropyl orthosilicate. Preferably, the silicon source is ethyl orthosilicate.

In a specific embodiment, the ammonia source comprises one or more of 3-aminopropyl triethoxysilane, 3-aminopropyl trimethoxysilane, N- (2-aminoethyl) -3-aminopropyl triethoxysilane, and gamma-aminopropyl diethoxymethylsilane. Preferably, the ammonia source is 3-aminopropyl triethoxysilane.

In a specific embodiment, the solvent in step (2) includes one or more of chlorobenzene, cyclohexane, chloroform, dichloromethane, and water.

In a specific embodiment, the preparation method of the aminated dendritic mesoporous silica specifically comprises the steps of adding a template agent and a catalyst into water, mixing for 10 min-30 min at 40-60 ℃ to form a water phase, adding a chlorobenzene solution containing a silicon source, wherein the mass ratio of the template agent to the catalyst to the silicon source is (20-30) (0.5-1.2) (6-12), mixing for 12 h-36 h at 40-60 ℃, centrifuging, drying, calcining for 4 h-8 h at 300-600 ℃ to obtain the dendritic mesoporous silica, adding the dendritic mesoporous silica and the ammonia source into an acetonitrile solution according to the mass ratio of (0.08-0.1) (50-100), and reacting for 8 h-16 h at 60-85 ℃ to obtain the aminated dendritic mesoporous silica.

In a specific embodiment, the present invention is not particularly limited in the mixing manner, and the raw materials may be uniformly mixed.

The invention also discloses an anti-tumor drug, and the active ingredient is a novel nano preparation containing the gingerol A.

The following are specific examples

Example 1 preparation of novel nano-formulations containing zingibenone A (GA@AMSN)

Preparation of MSN 30g N-hexadecyltrimethylammonium chloride (CTAC) was dissolved in a 500mL round bottom flask using 300mL of ultra pure water, then 1.0g of triethanolamine was added to the dissolved CTAC solution and mixed with thorough stirring to form the upper aqueous phase. Then, 12mL of tetraethyl silicate was thoroughly mixed with 100mL of a solvent (60 mL of cyclohexane+40 mL of chlorobenzene) in a beaker to prepare an oil phase. The oil phase was transferred to a flask to form a two-phase reaction system. The reaction was maintained at a stirring speed of 300rpm/min at 60℃for 12h. Taking out the milky white liquid, centrifuging (10000 r/min,15 min), and finally obtaining white solid product, washing the product with ethanol three times to remove solvent, and drying in air to obtain white powder. The white powder was placed in a muffle furnace, calcined at 550 ℃ for 6h to remove CTAC, the obtained product was washed once with deionized water and ethanol, and vacuum dried to obtain MSN with specific surface area up to 926.3128m ²/g, pore diameter 8.5612nm and pore volume of 3.374020cm ³/g.

AMSN preparation 200mg of MSN were added to 40mL of acetonitrile for ultrasonic dispersion, 200. Mu.l of 3-aminopropyl triethoxysilane (APTE) were added to the above reaction system, and the reaction was stirred at 600rpm at 80℃for 12 hours. After the reaction was completed, the liquid was centrifuged, and the obtained samples were washed twice with water and ethanol, respectively, to obtain AMSN.

GA@AMSN preparation 40mg AMSN was added to 5mL of GA in acetonitrile (5 mg/mL, 10mg/ML, 15 mg/mL). The mixture was sonicated and incubated at room temperature for 8h with stirring. Then, centrifugation was performed and the supernatant was removed, the product was collected, washed three times with deionized water and dried under vacuum to give ga@amsn.

Example 2GA@AMSN in vitro tumor cell Activity experiment

1. Experimental cell

A431 human epidermal carcinoma cells, a375 human malignant melanoma cells, caco2 human colon adenocarcinoma cells, SW579 human thyroid squamous carcinoma cells, HCT-116 human colorectal carcinoma cells, hepG2 human liver carcinoma cells were purchased from the national academy of sciences' typical culture storage committee cell bank.

2. Experimental method

Tumor cell proliferation experiments were performed by MTT experiments, and the effect of ga@amsn prepared in example 1 on cell proliferation was analyzed. Cells are paved into a 96-well plate according to 1X 10 ⁴ cells/well, 100 mu L of culture medium which contains GA@AMSN and GA with corresponding drug concentration (5 mu M-25 mu M) is respectively added after the cells are attached, 6 compound wells are arranged at each concentration, and the error of each result of each well is not more than 5%. After 24h drug action, 100. Mu.l of 5mg/ml MTT solution was added to each well of the culture supernatant in the wells, and the culture was terminated after further incubation for 3 hours, taking care to discard the culture supernatant in the wells. The crystals were dissolved by adding 100. Mu.l DMSO per well. The light absorption value of each well was measured at 490nm wavelength by an enzyme-linked immunosorbent assay, and the IC50 value was calculated.

As shown in the results of figures 1-6, the GA@AMSN has good synergistic inhibition effect, and can inhibit proliferation of A431 human epidermal carcinoma cells, A375 human malignant melanoma cells, caco2 human colon adenocarcinoma cells, SW579 human thyroid squamous carcinoma cells, HCT-116 human colorectal carcinoma cells and HepG2 human liver carcinoma cells in a dose-dependent manner after 24 hours of effect.

Example 3GA@AMSN mouse tumor model experiment situation

According to the experimental results of example 2, the effect of ga@amsn on a375 melanoma is compared with that of the positive drug in this example as follows:

1. Experimental animals:

NU/NU mice, females, 6-8 weeks, 18-22g, purchased from viviparid laboratory animal technologies limited. All experimental mice were housed in Shanghai Lidi SPF-class animal houses and were acclimatized for at least 3 days in advance. All experimental mice are fed into an IVC constant temperature and constant pressure system of an SPF-class animal house, wherein the temperature is 20-26 ℃, the humidity is 40-70%, the illumination period is 12 hours, and the illumination period is 12 hours and is dark. And raising no more than 6 mice in each cage box, wherein the size of the cage box is 325mm multiplied by 210mm multiplied by 180mm, and the cage box is filled with the padding material which is autoclaved corncob, and the replacement is carried out twice a week. During the whole experimental process, all experimental mice can eat and drink freely, the feed is sterilized by Co60 irradiation, and the drinking water is sterilized under high pressure, so that the feed and the drinking water are kept in sufficient supply.

2. Design of experiment

2.1 Culture of A375 tumor cells

A375 cells were cultured in a culture medium of 90% DMEM+10% inactivated FBS at 37℃in a 5% CO ₂ incubator. Cells in the logarithmic growth phase will be used for in vivo establishment of a model of the graft tumor.

2.2, Inoculation of A375 tumor cells

Taking A375 cells in logarithmic growth phase, adding appropriate amount of HBSS, re-suspending, counting, adjusting cell density to 4×10 ⁷ cells/mL, and placing on ice for standby. Each NU/NU mouse was inoculated subcutaneously on the right with 0.1mL of tumor cell suspension, 4X 10 ⁶ cells/mouse. 15 mice with average tumor volume of 109.65 (84.69-136.81) mm ³ are selected for pharmacodynamic grouping, and randomly divided into 3 groups of 5 mice. The 3 groups were given PBS, jiang Xitong A nano-preparation (GA@AMSN), positive control drug Darafenib (Dabrafenib), respectively. Detailed methods of administration, doses and routes of administration are shown in Table 1, with day 0 being the day of group administration.

TABLE 1 grouping and administration

Dosing volume adjustment of dosing volume according to tumor-bearing mouse body weight (10. Mu.L/g)

3. Evaluation index

Mainly, a375 cell line subcutaneous transplantation tumor is established, and the antitumor activity of the tested drugs on the model is evaluated.

3.1 Tumor volume measured twice weekly using vernier calipers, the tumor volume calculation formula was v=0.5× (a×b ²), where a, b represent the long and short diameters of the tumor, respectively.

3.2 Tumor growth inhibition ratio TGI (%) = [1- (Ti-T0)/(Vi-V0) ]x100

Wherein Ti is the average tumor volume after the compound group starts to be administered, T0 is the average tumor volume when the compound group starts to be administered for the first time, V0 is the average tumor volume when the solvent control group starts to be administered for the first time, and Vi is the average tumor volume after the solvent control group starts to be administered.

3.3 Relative tumor proliferation rate T/C (%) the formula was as follows: T/C% = TRTV/CRTV X100% (TRTV: treatment group RTV; CRTV: negative control group RTV). The relative tumor volume (relative tumor volume, RTV) was calculated from the results of the tumor measurements, with the calculation formula rtv=vt/V0, where V0 is the average tumor volume measured at the time of group administration (i.e. d 0), vt is the average tumor volume at a certain measurement, and TRTV and CRTV take the same day data.

3.4 All tumor bearing mice body weights were measured twice weekly. The change in weight gain of mice after administration was also calculated as RCBW (%) = (BWi-BW 0)/bw0×100, BWi being the average weight after the start of administration and BW0 being the average weight at the time of the first administration.

4. Data analysis

All data were analyzed using Graphpad and expressed as mean±sem. The difference between the test drug group and the control group was compared by One-way ANOVA LSD (L) test, and p <0.05 was considered to be a significant difference.

5. Results

On day 21 of the group administration, the average tumor volume of the model control group (PBS) was 2075.28 + -384.4 mm ³, the average tumor volumes of the GA@AMSN,100mg/kg administration group and Dabrafenib, and 100mg/kg administration group were 1184.15 + -212.76 mm ³、1211.51±130.65mm³, respectively, and the tumor growth inhibition ratio (TGI%) was 45.34% and 43.95% respectively, compared with the model control group, and all administration groups were able to inhibit the growth of subcutaneous transplantation tumor of A375 mice, but showed no statistical significance (p > 0.05). On day 25 of the group administration, the average tumor volumes of GA@AMSN,100mg/kg administration group and Dabrafenib,100mg/kg administration group were 1900.7.+ -. 384.05mm ³、1985.26±230.72mm³, respectively, as shown in Table 2 and FIG. 7.

On day 21 of the group dosing, the average tumor volume of the model control mice exceeded 2000mm ³, which was euthanized directly on the day in view of the requirements of the humane end point. The whole experiment was ended on day 25 of dosing, all mice in GA@AMSN,100mg/kg dosing group and Dabrafenib,100mg/kg dosing group were euthanized, tumor removed and photographed by weighing. The average tumor weight of the model control group was 2.11.+ -. 0.36g (day 21), and the average tumor weights of GA@AMSN,100mg/kg of the administration group, dabrafenib,100mg/kg of the administration group were 2.02.+ -. 0.41g (day 25), and 2.07.+ -. 0.27g (day 25), respectively. Tumor volume was substantially consistent with tumor weight results, see table 3 and fig. 7.

In addition, in this experiment, all mice did not see sustained weight loss and other abnormal symptoms, indicating that tumor-bearing mice were tolerant to the drug under the dose of the agent, as shown in table 4 and fig. 8.

Table 2 average tumor volume (mean.+ -. SEM) for mice in each group

Note that p <0.05 is considered a significant difference compared to the control group.

TABLE 3 average weight of tumor for each group of mice (mean.+ -. SEM)

Note that p <0.001, p <0.0001, p <0.05 are considered significant differences compared to the control group

TABLE 4 weight variation of mice in each group (mean.+ -. SEM)

From the above experimental results, jiang Xitong a nano-preparation has strong inhibition effect on proliferation of melanoma a375, which may be related to its specific recognition ability with cancer cells. After 21 days of administration, the tumor growth inhibition rate (TGI%) of Jiang Xitong A nano-preparation is 45.34%, which is better than 43.95% of positive drug Darafenib, and after 25 days of administration, the data of Jiang Xitong A nano-preparation in the aspects of average tumor volume, average tumor weight and weight change rate of mice are better than that of positive drug Darafenib, the effect of inhibiting melanoma A375 is obvious, and the nano-preparation GA@AMSN has great application potential in the anti-melanoma treatment field.

Further, GA@AMSN,100mg/kg of the liver of the administration group was collected for paraffin section, and the morphology of cells and tissues was evaluated by H & E staining analysis. The results of the H & E staining experiments are shown in FIG. 9, and the liver tissue structure is found to be free from obvious abnormality, the sink region is not found to be fibroplatic and mononuclear inflammatory cell infiltration, and the liver parenchyma is not found to be clear in focal necrosis and lamellar necrosis. No clear liver Dou Yuxie and bile stasis are found, and no clear histological manifestation of liver tissue damage is found.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the claims. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (10)

1. The application of a novel nano preparation containing gingerol A in preparing antitumor drugs is characterized in that the nano preparation comprises amino dendritic mesoporous silica and Jiang Xitong A loaded on the amino dendritic mesoporous silica.

2. The use according to claim 1, wherein the tumor comprises one or more than two of melanoma, lymphohematopoietic tumor, endocrine tumor, lung and mediastinal tumor, breast tumor, digestive system tumor, urinary and male reproductive system tumor, female reproductive system tumor, head and neck tumor, central nervous system tumor, skin tumor and bone and soft tissue.

3. The use according to claim 1, wherein the dosage form of the medicament comprises a tablet, capsule, pill, injection, sustained release formulation or controlled release formulation;

The administration route of the antitumor drug comprises one or more of intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration _、 rectal administration, skin mucosa administration and inhalation administration.

4. The use according to claim 1, wherein the dose of the nano-preparation in the antitumor drug is 100 mg/kg-400 mg/kg.

5. The use according to claim 1, wherein the anti-tumor drug is a drug that inhibits tumor growth or inhibits proliferation of tumor cells.

6. The use according to claim 1, wherein the anti-tumor drug is a drug that promotes or induces apoptosis in tumor cells.

7. The use according to claim 1, wherein the antineoplastic agent is an agent which inhibits the growth of a transplanted tumor.

8. The use according to any one of claims 1 to 7, wherein the antitumor drug further comprises a pharmaceutically acceptable carrier, excipient and/or adjuvant.

9. The use according to claim 1, characterized in that the preparation method of the nano-formulation comprises:

and dissolving Jiang Xitong A in a solvent to obtain Jiang Xitong A solution, adding the Jiang Xitong A solution and the aminated dendritic mesoporous silica into a buffer solution for reaction to load the gingerol A on the aminated dendritic mesoporous silica, and obtaining the nano preparation.

10. An antitumor drug is characterized in that the functional component is a novel nano preparation containing gingerol A;

the nanofabric is a nanofabric for use according to any one of claims 1-9.