A heteropolyacid / bio-polyamine self-assembled crystal, its preparation method and application

Abstract

The present invention discloses a heteropolyacid / biopolyamine self-assembled crystal, a preparation method thereof and an application thereof. In the present invention, a heteropolyacid and / or a heteropolyacid derivative, a biopolyamine and / or a biopolyamine derivative, and a surfactant are added to a solvent and mixed uniformly to form a mixed solution, and the crystal is obtained through reaction. The preparation method of the crystal is simple and can be used for large-scale production and preparation, providing new ideas and methods for the development of novel and highly efficient anti-tumor drugs.

Description

Technical Field

[0001] The present invention relates to the field of preparation of heteropolyacid delivery systems, and specifically relates to a heteropolyacid / biopolyamine self-assembled crystal, a preparation method thereof, and an application thereof. Background Art

[0002] In order to reduce the toxicity of polyoxometalates (POMs) and improve their bioavailability, the prior art mainly modifies and encapsulates POMs with organic or inorganic substances to prepare POM-based composite materials. For example, lanthanide POMs have good water solubility, biocompatibility, and low cytotoxicity, and are excellent luminescent materials in the field of biomedical imaging. Existing research uses mesoporous silica as the core, pH / temperature-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA) and lanthanide POMs as the dual-responsive shell and luminescent label respectively to form a composite material. Cell imaging shows that the composite material has good red luminescence and biocompatibility. Due to its dual-responsive release ability and unique luminescent properties, this composite material system has potential application prospects in the delivery of triggerable drugs (Mater Chem Phys. 2020; 239:121994). Kong X et al. formed a structurally stable and narrow-sized ion complex in the NIR-II region through the strong ion complexation between POMs-[(NH4)6P2Mo 18 O 62 ·12H2O and 3,3',5,5'-tetramethylbenzidine (TMB), improved its specific accumulation in the tumor region, and achieved passive targeting in an acidic environment.

[0003] Currently, although a variety of drug carriers, such as chitosan, mesoporous silica, and various organic materials, have been explored for the delivery system of polyoxometalates (POMs), challenges still remain in improving the loading efficiency of POMs, simplifying the carrier preparation process, and enhancing the functionality of the carrier. In addition, many existing carriers are non-functional carriers, which not only increases the complexity of the drug-loading system preparation, but also exacerbates the potential toxic side effects of the POMs delivery system and the metabolic burden on the body. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a heteropolyacid / biopolyamine self-assembled crystal, a preparation method thereof, and an application thereof. The present invention prepares a crystal with a biologically active carrier in a simple and efficient manner. The biopolyamine as a carrier not only avoids the toxic side effects and metabolic burden of the delivery system, but also is beneficial to improving biological activity.

[0005] To solve the above technical problem, the first aspect of the present invention is to provide a preparation method of a heteropolyacid / biopolyamine self-assembled crystal, which specifically includes the following steps:

[0006] Add the heteropolyacid and / or heteropolyacid derivative, biogenic polyamine and / or biogenic polyamine derivative into a solvent and mix them evenly to form a mixed solution, and react to obtain the crystals.

[0007] Furthermore, the mixed solution needs to be continuously stirred. The stirring process can accelerate the formation of crystals and form crystals with a uniform morphology.

[0008] Furthermore, the heteropolyacid is selected from one or more of sodium metatungstate, sodium phosphomolybdate, sodium phosphotungstate, ammonium phosphomolybdate and ammonium metatungstate.

[0009] Furthermore, the biogenic polyamine is selected from one or more of spermidine, spermine, cadaverine and putrescine.

[0010] Furthermore, it also includes adding a surfactant to the mixed solution.

[0011] Furthermore, the surfactant is selected from one or more of polyvinylpyrrolidone, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, alkyl alcohol amide, polyglycerol fatty acid ester, sodium dodecylsulfonate, sodium dodecylbenzenesulfonate, polyethylene glycol, Tween and sucrose fatty acid ester.

[0012] Preferably, the surfactant is selected from one or more of polyvinylpyrrolidone, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, alkyl alcohol amide and polyglycerol fatty acid ester.

[0013] Furthermore, the solvent is selected from water, organic solvent or a mixed solvent formed by water and organic solvent; the present invention does not strictly limit the type of solvent, and the purpose of using the solvent is to dissolve the heteropolyacid, biogenic polyamine and surfactant; preferably, the solvent is water.

[0014] Furthermore, the temperature of the reaction is higher than the freezing point of the mixed solution, preferably 0-120 °C. If the reaction temperature is too low, it will affect the self-assembly rate between the crystals; if the reaction temperature is too high, it will cause unnecessary energy consumption. Therefore, it is most suitable to select from 0-120 °C. The reaction process of crystal self-assembly is not limited to the reaction pressure and atmosphere, and there is no strict limit whether it is high or low pressure, inert atmosphere or air.

[0015] Furthermore, the reaction time is 5 min-30 d.

[0016] Furthermore, the molar ratio of the heteropolyacid and / or heteropolyacid derivative to the biogenic polyamine and / or biogenic polyamine derivative in the mixed solution is not greater than 1:0.3; preferably 1:(0.3-100), such as 1:0.3, 1:0.5, 1:1, 1:4, 1:10, 1:12 and 1:100, etc., including but not limited to the above-listed molar ratios.

[0017] Preferably, a heteropolyacid, a biogenic polyamine, and a surfactant are added to a solvent, and uniformly mixed to form a mixed solution, and the crystal is obtained by reaction.

[0018] The second aspect of the present invention is to provide a heteropolyacid / biogenic polyamine self-assembled crystal prepared by the method described in the first aspect.

[0019] The third aspect of the present invention is to provide the application of the heteropolyacid / biogenic polyamine self-assembled crystal described in the second aspect in the preparation of a drug for treating tumors.

[0020] Furthermore, the tumors include but are not limited to esophageal cancer, head and neck cancer, nasopharyngeal cancer, ovarian cancer, lung cancer, gastric cancer, breast cancer, liver cancer, pancreatic cancer, colon cancer, skin cancer, cholangiocarcinoma, bladder cancer, and kidney cancer. Preferably, it is colon cancer.

[0021] Furthermore, the administration method of the drug is intratumoral injection. The drug can be combined with radiotherapy to enhance the therapeutic effect on tumors.

[0022] Advantages of the present invention:

[0023] 1. Compared with the strategy of modifying and delivering heteropolyacids with non-functional organic substances in the prior art, the present invention first uses biogenic polyamines as carriers to load heteropolyacids, and utilizes the electrostatic force and van der Waals force between heteropolyacids and biogenic polyamines to self-assemble into nanocrystals, which can not only greatly improve the loading efficiency of heteropolyacids, but also biogenic polyamines as carriers have no toxic side effects and will not increase the metabolic burden of the body. In addition, biogenic polyamines can enhance the functions of immune cells such as CD8 + T cells to effectively activate anti-tumor immunity, and the self-assembled crystals formed by biogenic polyamines and heteropolyacids can greatly improve the anti-tumor immune response induced by radiotherapy, thereby effectively improving the tumor treatment effect.

[0024] 2. The preparation method of the crystal of the present invention is simple and efficient, and can be prepared on a large scale; the prepared crystal has a high thermal decomposition temperature, and the crystals of different batches have high consistency and stability during batch production. Description of the Drawings

[0025] Figure 1 is a characterization diagram of the sodium metatungstate / spermidine crystal prepared in Example 1 of the present invention; among them, Figure 1 a in is a scanning electron micrograph, Figure 1 b in is an X-ray powder diffraction pattern, Figure 1 c in is a Fourier transform infrared spectrum, Figure 1 d in is a thermogravimetric analysis diagram;

[0026] Figure 2 is a characterization diagram of the sodium metatungstate / spermine crystal prepared in Example 2 of the present invention; among them, Figure 2In which, a is a scanning electron microscope image, Figure 2 b is an X-ray powder diffraction pattern, Figure 2 c is a Fourier transform infrared spectrum, Figure 2 d is a thermogravimetric analysis chart;

[0027] Figure 3 It is a characterization diagram of sodium metatungstate / putrescine crystals prepared in Example 3 of the present invention; among them, Figure 3 a is a scanning electron microscope image, Figure 3 b is an X-ray powder diffraction pattern, Figure 3 c is a Fourier transform infrared spectrum, Figure 3 d is a thermogravimetric analysis chart;

[0028] Figure 4 It is a characterization diagram of sodium metatungstate / cadaverine crystals prepared in Example 4 of the present invention; among them, Figure 4 a is a scanning electron microscope image, Figure 4 b is an X-ray powder diffraction pattern, Figure 4 c is a Fourier transform infrared spectrum, Figure 4 d is a thermogravimetric analysis chart;

[0029] Figure 5 It is the single crystal analysis and simulation calculation of sodium metatungstate / spermine prepared in Example 1 of the present invention; among them Figure 5 a is the structure of the crystal, Figure 5 b is the bonding group inside the crystal, Figure 5 c is the intermolecular interaction energy inside the crystal;

[0030] Figure 6 It is the tumor volume change curve of different groups of mice in the test example of the present invention;

[0031] Figure 7 It is the body weight change curve of different groups of mice in the test example of the present invention;

[0032] Figure 8 It is the treatment survival curve of different groups of mice in the test example of the present invention. Detailed implementation manners

[0033] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the examples given are not intended to limit the present invention.

[0034] In this specification, the meaning of sodium metatungstate (14.93 mg, 0.005 mmol) is a general term for adding 14.93 mg of sodium metatungstate to make its final concentration in water 0.005 mmol / L; the same applies to other similar expressions.

[0035] Example 1

[0036] Sodium metatungstate (14.93 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min at 26 °C with a magnetic stirrer, spermidine (0.73 mg, 0.005 mmol) was added. Stirring was continued at 26 °C for 6 min. After the reaction was completed, precipitation was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium metatungstate / spermidine self-assembled crystals.

[0037] As Figure 1 shown in a), the scanning electron micrograph of the prepared sodium metatungstate / spermidine self-assembled crystals was obtained; it was found that the longitudinal size of the crystals was 2.2 ± 0.5 μm and the transverse size was 0.8 ± 0.2 μm. Figure 1 The XRD diffraction peaks tested in b) indicate that the prepared product has a crystal structure. Figure 1 The Fourier transform infrared spectrum in c) shows that the characteristic peaks at 3100 cm -1 and 1460 cm -1 wavelengths are N-H and C-H, respectively; the thermogravimetric analysis graph ( Figure 1 shown in d)) shows that the assembled crystals have excellent thermal stability and the thermal decomposition temperature is 280 °C.

[0038] Example 2

[0039] Sodium metatungstate (14.93 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min at 18 °C with a magnetic stirrer, spermine (0.51 mg, 0.0025 mmol) was added. Stirring was continued at 18 °C for 2 h. After the reaction was completed, precipitation was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium metatungstate / spermine self-assembled crystals.

[0040] As Figure 2 shown: The scanning electron micrograph of the sodium metatungstate / spermidine self-assembled crystals shows that the longitudinal size of the crystals is 4.5 ± 1 μm and the transverse size is 0.8 ± 0.2 μm. And it has a thermal decomposition temperature of 280 °C.

[0041] Example 3

[0042] Sodium metatungstate (14.93 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring with a magnetic stirrer at 6 °C for 30 min, cadaverine (2.56 mg, 0.025 mmol) was added. The reaction was continued with stirring at 6 °C for 12 h. After the reaction was completed, precipitation was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium metatungstate / cadaverine self-assembled crystals.

[0043] As Figure 3 shown: The scanning electron micrograph of sodium metatungstate / spermidine self-assembled crystals shows that the longitudinal size of the crystals is 4.8 ± 1.5 μm and the transverse size is 1 ± 0.3 μm; and it has a thermal decomposition temperature of 320 °C.

[0044] Example 4

[0045] Sodium metatungstate (14.93 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring with a magnetic stirrer at 0 °C for 30 min, putrescine (4.40 mg, 0.05 mmol) was added. The reaction was continued with stirring at 0 °C for 2 d. After the reaction was completed, precipitation was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium metatungstate / putrescine self-assembled crystals.

[0046] As Figure 4 shown: The scanning electron micrograph of sodium metatungstate / spermidine self-assembled crystals shows that the longitudinal size of the crystals is 1.2 ± 0.2 μm and the transverse size is 180 ± 50 nm; and it has a thermal decomposition temperature of 220 °C.

[0047] Example 5

[0048] Sodium phosphomolybdate (9.46 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring with a magnetic stirrer at 40 °C for 30 min, spermidine (0.73 mg, 0.005 mmol) was added. The reaction was continued with stirring at 40 °C for 20 min. After the reaction was completed, precipitation was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphomolybdate / spermidine self-assembled crystals.

[0049] Example 6

[0050] Sodium phosphomolybdate (9.46 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min with a magnetic stirrer at 50 °C, spermine (6.06 mg, 0.03 mmol) was added. Stirring was continued at 50 °C for 18 h. After the reaction was completed, precipitation was obtained by centrifugation (14,800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphomolybdate / spermine self-assembled crystals.

[0051] Example 7

[0052] Sodium phosphomolybdate (9.46 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min with a magnetic stirrer at 60 °C, cadaverine (7.68 mg, 0.075 mmol) was added. Stirring was continued at 60 °C for 32 h. After the reaction was completed, precipitation was obtained by centrifugation (14,800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphomolybdate / cadaverine self-assembled crystals.

[0053] Example 8

[0054] Sodium phosphomolybdate (9.46 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min with a magnetic stirrer at 70 °C, putrescine (8.80 mg, 0.10 mmol) was added. Stirring was continued at 70 °C for 12 h. After the reaction was completed, precipitation was obtained by centrifugation (14,800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphomolybdate / putrescine self-assembled crystals.

[0055] Example 9

[0056] Sodium phosphotungstate (14.73 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water, and after stirring for 30 min with a magnetic stirrer at 80 °C, spermidine (2.92 mg, 0.02 mmol) was added. Stirring was continued at 80 °C for 18 h. After the reaction was completed, precipitation was obtained by centrifugation (14,800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphotungstate / spermidine self-assembled crystals.

[0057] Example 10

[0058] Sodium phosphotungstate (14.73 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water. After stirring for 30 min with a magnetic stirrer at 90 °C, spermine (12.12 mg, 0.06 mmol) was added. The reaction was continued with stirring at 90 °C for 24 h. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphotungstate / spermine self-assembled crystals.

[0059] Example 11

[0060] Sodium phosphotungstate (14.73 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water. After stirring for 30 min with a magnetic stirrer at 100 °C, cadaverine (2.56 mg, 0.025 mmol) was added. The reaction was continued with stirring at 100 °C for 12 h. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphotungstate / cadaverine self-assembled crystals.

[0061] Example 12

[0062] Sodium phosphotungstate (14.73 mg, 0.005 mmol) and polyvinylpyrrolidone (0.56 mg, 0.005 mmol) were added to water. After stirring for 30 min with a magnetic stirrer at 26 °C, putrescine (2.20 mg, 0.025 mmol) was added. The reaction was continued with stirring at 26 °C for 6 d. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium phosphotungstate / putrescine self-assembled crystals.

[0063] Example 13

[0064] Ammonium phosphomolybdate (9.38 mg, 0.005 mmol) and fatty alcohol polyoxyethylene ether (15.24 mg, 0.005 mmol) were added to water. After stirring for 30 min with a magnetic stirrer at 26 °C, spermidine (7.3 mg, 0.05 mmol) was added. The reaction was continued with stirring at 26 °C for 12 d. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphomolybdate / spermidine self-assembled crystals.

[0065] Example 14

[0066] Ammonium phosphomolybdate (9.38 mg, 0.005 mmol) and alkylphenol polyoxyethylene ether (9.53 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, spermine (20.2 mg, 0.1 mmol) was added. The reaction was continued with stirring at 26 °C for 18 d. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphomolybdate / spermine self-assembled crystals.

[0067] Example 15

[0068] Ammonium phosphomolybdate (9.38 mg, 0.005 mmol) and alkylolamide (13.74 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, cadaverine (51.2 mg, 0.5 mmol) was added. The reaction was continued with stirring at 26 °C for 24 d. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphomolybdate / cadaverine self-assembled crystals.

[0069] Example 16

[0070] Ammonium phosphomolybdate (9.38 mg, 0.005 mmol) and alkylolamide (13.74 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, putrescine (17.6 mg, 0.2 mmol) was added. The reaction was continued with stirring at 26 °C for 30 d. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphomolybdate / putrescine self-assembled crystals.

[0071] Example 17

[0072] Ammonium phosphotungstate (14.66 mg, 0.005 mmol) and polyglycerol fatty acid ester (20.70 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 48 °C for 30 min, spermidine (2.92 mg, 0.02 mmol) was added. The reaction was continued with stirring at 48 °C for 16 h. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphotungstate / spermidine self-assembled crystals.

[0073] Example 18

[0074] Ammonium phosphotungstate (14.66 mg, 0.005 mmol) and polyglyceryl fatty acid ester (20.70 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 36 °C for 30 min, spermine (6.06 mg, 0.3 mmol) was added. The reaction was continued by stirring at 36 °C for 12 h. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain ammonium phosphotungstate / spermine self-assembled crystals.

[0075] Example 19

[0076] Sodium metatungstate (149.3 mg, 0.05 mmol) and polyvinylpyrrolidone (5.6 mg, 0.05 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, the mixed solution was transferred to a 25 mL polytetrafluoroethylene liner, and putrescine (4.40 mg, 0.05 mmol) was added to the liner. The liner was placed in a hydrothermal reaction kettle and reacted at 120 °C for 12 h. After the reaction was completed, the precipitate was obtained by centrifugation (14800 rpm, 10 min). The precipitate was washed three times with deionized water to obtain sodium metatungstate / putrescine self-assembled crystals.

[0077] Comparative Example 1

[0078] Ammonium phosphotungstate (14.66 mg, 0.005 mmol) and polyglyceryl fatty acid ester (20.70 mg, 0.005 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, spermine (0.0202 mg, 0.001 mmol) was added. The reaction was continued by stirring at 26 °C for 30 d, and no self-assembled crystals were formed.

[0079] Comparative Example 2

[0080] Ammonium phosphomolybdate (938 mg, 0.5 mmol) and alkylolamide (1374 mg, 0.5 mmol) were added to water. After stirring with a magnetic stirrer at 26 °C for 30 min, putrescine (1.76 mg, 0.02 mmol) was added. The reaction was continued by stirring at 26 °C for 30 d, and no self-assembled crystals were formed.

[0081] Test Example

[0082] To explore the internal reasons and formation methods of crystal formation, by analyzing the single crystal of sodium metatungstate / spermine and performing simulation calculations as Figure 5 shown, the sodium metatungstate / spermine crystal has a parallelogram structure ( Figure 5 a) in it), and the main bonding between sodium metatungstate and spermine inside the crystal is through the H on the N-containing functional group and O to form a bond ( Figure 5In b), there are electrostatic interactions and van der Waals interactions, and the molecules self-assemble to form crystals in the form of supramolecular forces ( Figure 5 In c).

[0083] Experimental conditions: 30 mice were randomly divided into 6 groups, namely the blank group, the sodium metatungstate / spermine + radiation group, the sodium metatungstate / spermine group, the simple radiation group, the sodium metatungstate + radiation group, and the spermine + radiation group; all mice were subcutaneously injected with CT26 tumor cells in the back, and treatment was carried out when the tumor cells grew to 80 - 100 mm 2 . Mice in the sodium metatungstate / spermine + radiation group and the sodium metatungstate / spermine group were respectively injected with 10.79 mg / kg of sodium metatungstate / spermine, mice in the sodium metatungstate + radiation group were injected with 10.29 mg / kg of sodium metatungstate, and mice in the spermine + radiation group were injected with 0.5 mg / kg of spermine reagent. On the same day, the 6 groups of mice were irradiated with X-rays at a dose of 5 Gy / mouse, and the tumor volume and weight were measured every other day.

[0084] The test results are as Figures 6 - 8 shown. The treatment by combining the crystals prepared in the present invention with radiotherapy has an obvious inhibitory effect on tumors, improves the survival rate of mice and has little impact on the body weight of mice.

[0085] The above embodiments are only preferred embodiments given to fully illustrate the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present invention are all within the protection scope of the present invention. The protection scope of the present invention is subject to the claims.

Claims

1. Use of a heteropolyacid / bio-polyamine self-assembled crystal in the preparation of a drug for treating colon cancer, characterized in that, The preparation method of the heteropolyacid / biopolyamine self-assembled crystal comprises the following steps: adding a heteropolyacid and a biopolyamine into a solvent and mixing uniformly to form a mixed solution, and reacting to obtain the crystal, wherein the heteropolyacid is sodium metatungstate and the biopolyamine is spermine.

2. The application according to claim 1, wherein The preparation method further comprises adding a surfactant into the mixed solution.

3. The application according to claim 1, characterized in that The temperature of the reaction is higher than the freezing point of the mixed solution.

4. The application according to claim 1, characterized in that, The reaction time is 5 minutes to 30 days.

5. The application according to claim 1, wherein The molar ratio of the heteropolyacid to the biopolyamine in the mixed solution is not greater than 1:0.3.

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