Traditional Chinese medicine self-assembled nano material as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biomedical engineering, and relates to a traditional Chinese medicine self-assembled nano material as well as a preparation method and application thereof. The traditional Chinese medicine self-assembled nano material is prepared from mineral traditional Chinese medicines and other traditional Chinese medicines, wherein the other traditional Chinese medicines are one or two of plant-derived traditional Chinese medicines and animal-derived traditional Chinese medicines; the traditional Chinese medicine self-assembled nano material has a T1 weighted nuclear magnetic resonance imaging function; the D50 particle size of the traditional Chinese medicine self-assembled nano material is 30 to 450 nm. The traditional Chinese medicine self-assembled nano material provided by the invention is high in biological safety and good in storage stability, has a T1 weighted nuclear magnetic resonance imaging function, and also has a treatment effect on specific tumors.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical engineering, and relates to a traditional Chinese medicine self-assembly nano material and a preparation method and application thereof. Background Art

[0002] Magnetic resonance imaging (MRI), as a non-invasive and high-resolution medical imaging technology, occupies a key position in modern medical diagnosis. Contrast agents play a key role in enhancing imaging contrast and highlighting diseased tissues, greatly helping doctors to accurately identify diseases. At present, most of the mainstream contrast agents on the market are chemically synthesized products. For example, gadolinium-based contrast agents are widely used in the field of T1-weighted imaging due to their unique magnetic properties; superparamagnetic iron oxide nanomaterials also have exclusive imaging uses for specific tissues or diseases, such as breast cancer, gastric cancer, and liver cancer. However, this type of chemical synthetic contrast agent has many defects that are difficult to ignore. In terms of stability, they have strict requirements on the storage environment and are usually inseparable from low temperature conditions, which undoubtedly raises the storage and transportation costs, and even at a suitable low temperature, their validity period is still relatively short, and they often encounter problems such as degradation and agglomeration, which greatly reduces the contrast effect; from the perspective of biosafety, some chemical contrast agents can induce serious adverse reactions such as nephrogenic systemic fibrosis, which limits the use of special groups such as patients with renal insufficiency.

[0003] As a treasure of the Chinese nation, traditional Chinese medicine has a history of thousands of years of application. It contains rich and diverse natural ingredients, and its pharmacological effects are also very complex and subtle. Traditional Chinese medicine is derived from natural plants, animals, and minerals. It has rich and complex ingredients and contains many substances with unique physiological activities. Moreover, it has been clinically verified for a long time and has high safety. For a long time, the application of traditional Chinese medicine has been confined to traditional dosage forms such as oral decoctions, pills, and powders to achieve the purpose of regulating the functions of the body's internal organs. In the field of modern cutting-edge medical imaging, especially the development of contrast agents, it is still in its infancy, and a lot of potential value needs to be explored. Summary of the invention

[0004] In order to solve the above-mentioned problems existing in the prior art, one purpose of the present invention is to provide a self-assembled nanomaterial of traditional Chinese medicine, a second purpose is to provide a preparation method of the self-assembled nanomaterial of traditional Chinese medicine, and a third purpose is to provide an application of the self-assembled nanomaterial of traditional Chinese medicine to overcome the shortcomings of the prior art.

[0005] The first object of the present invention is achieved by the following technical solutions:

[0006] A Chinese medicine self-assembling nanomaterial, wherein the raw materials for preparing the Chinese medicine self-assembling nanomaterial include mineral Chinese medicine and other Chinese medicines, wherein the other Chinese medicines are one or both of plant-derived Chinese medicines and animal-derived Chinese medicines;

[0007] The traditional Chinese medicine self-assembled nanomaterial has T1-weighted nuclear magnetic resonance imaging function;

[0008] The D50 particle size of the traditional Chinese medicine self-assembled nano material is 30-450nm.

[0009] Preferably, the mineral Chinese medicine is one or more of natural copper, ochre, Yuyuliang, magnetite, and alum.

[0010] Preferably, the plant-derived Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis, Herba speranskiae radix, Rhizoma Anemarrhenae, Phellodendron amurense, Fructus Ligustri Lucidi, Angelica sinensis, Salvia miltiorrhiza, Citrus reticulatae, Astragalus membranaceus, and Artemisia argyi.

[0011] Preferably, the animal-derived Chinese medicinal materials are one or more of centipede, bezoar, musk, leech and earthworm.

[0012] Preferably, the Chinese medicine self-assembled nanomaterial has T1-weighted magnetic resonance imaging function for tumor tissue;

[0013] And / or, the D50 particle size of the traditional Chinese medicine self-assembled nanomaterial is 50 to 450 nm.

[0014] The second object of the present invention is achieved by the following technical solutions:

[0015] A method for preparing a traditional Chinese medicine self-assembly nanomaterial, the method comprising the following steps:

[0016] The mineral Chinese medicine, other Chinese medicines and water are mixed, and then heated for reaction, and then filtered, centrifuged, dialyzed and dried to obtain the Chinese medicine self-assembled nanomaterial;

[0017] The other traditional Chinese medicines are one or both of plant-derived traditional Chinese medicines and animal-derived traditional Chinese medicines.

[0018] Preferably, the mineral Chinese medicine is one or more of natural copper, ochre, Yuyuliang, magnetite, and alum; the plant-based Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis, Herba splendidae, Anemarrhena asphodeloides, Phellodendron chinense, Fructus Ligustri Lucidi, Angelica sinensis, Salvia miltiorrhiza, Citrus reticulata, Astragalus membranaceus, and Artemisia argyi; the animal-based Chinese medicine is one or more of centipede, bezoar, musk, leech, and earthworm.

[0019] Preferably, the mass ratio of the mineral Chinese medicine to other Chinese medicines is 1:0.1 to 1:10;

[0020] And / or, the ratio of the mass of water to the total mass of all Chinese medicines is 1 to 100:1.

[0021] Preferably, the preparation method further comprises the following steps before the heating reaction: standing for 1 to 60 minutes.

[0022] Preferably, the heating reaction temperature is 70 to 120° C., and the heating reaction time is 10 to 200 min.

[0023] Preferably, the centrifugation step comprises: performing 2 to 8 centrifugations, the first centrifugation speed is 1000 to 7000 rpm, the subsequent centrifugation speed is greater than the previous centrifugation speed, and the final centrifugation speed is 8000 to 15000 rpm; each centrifugation time is 5 to 50 minutes.

[0024] Preferably, the difference between the subsequent centrifugal speed and the previous centrifugal speed is 500-6000 rpm.

[0025] Preferably, the centrifugation step comprises: performing 3 to 5 centrifugations, the first centrifugation speed is 2000 to 5000 rpm, the difference between the subsequent centrifugation speed and the previous centrifugation speed is 1000 to 5000 rpm, and the final centrifugation speed is 9000 to 12000 rpm.

[0026] Preferably, the supernatant obtained by centrifugation is placed in a dialysis bag for dialysis, the molecular weight cutoff of the dialysis bag is 1000 to 10000 Da, and the dialysis time is 10 to 100 h.

[0027] Preferably, the drying is freeze drying or vacuum drying;

[0028] The freeze-drying temperature is -40 to -100°C, the vacuum degree is 1 to 100 Pa, and the time is 12 to 100 hours.

[0029] The third object of the present invention is achieved by the following technical solutions:

[0030] Application of the traditional Chinese medicine self-assembled nanomaterial in nuclear magnetic resonance contrast agent.

[0031] The application of the traditional Chinese medicine self-assembled nanomaterial in drugs for diagnosing and / or treating tumor diseases.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] 1. The Chinese medicine self-assembly nanomaterial provided by the present invention uses mineral Chinese medicine and other Chinese medicine as raw materials for preparation. Since the source is Chinese medicine, it has good biocompatibility and little side effect on the matrix;

[0034] 2. The Chinese medicine self-assembled nanomaterial provided by the present invention can be used as a nuclear magnetic resonance contrast agent, which aggregates in tumor tissues, significantly enhancing the T1-weighted MRI signal of tumor tissues, and is expected to accurately distinguish tumor boundaries from normal tissues;

[0035] 3. The traditional Chinese medicine self-assembled nanomaterial provided by the present invention has a D50 particle size of 30 to 450 nm. The contrast agent with a small particle size can more easily enter the tumor tissue and realize MRI imaging of the internal structure of the tumor;

[0036] 4. The Chinese medicine self-assembled nanomaterial provided by the present invention has the function of generating active oxygen free radicals under acidic conditions, has a killing effect on specific tumors, and can be used for the treatment of solid tumors;

[0037] 5. The Chinese medicine self-assembled nanomaterial of the present invention can be used as a nuclear magnetic resonance contrast agent, and can also have a killing effect on tumors, and can realize the integrated diagnosis and treatment of malignant tumors;

[0038] 6. The method for preparing the self-assembled nanomaterials of traditional Chinese medicine provided by the present invention uses mineral traditional Chinese medicine and other traditional Chinese medicine as the raw materials for preparation. The raw materials are safe and the synthesis process is simple, which can effectively reduce the cost. The self-assembled nanomaterials of traditional Chinese medicine prepared by the method can be stored at room temperature for up to 3 months and have high storage stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 a) particle size distribution and dispersion, and b) appearance in water of the traditional Chinese medicine self-assembled nanomaterials prepared in Examples 1 to 6 of the present invention.

[0040] Figure 2 This is a SEM image of the traditional Chinese medicine self-assembled nanomaterial prepared in Example 3 of the present invention.

[0041] Figure 3 The room temperature storage stability and multiple synthesized batch stability of the traditional Chinese medicine self-assembled nanomaterial prepared in Example 3 of the present invention.

[0042] Figure 4 The results of the CCK-8 experiment of the traditional Chinese medicine self-assembled nanomaterials prepared in Example 3 of the present invention in cells.

[0043] Figure 5 This is an H&E staining image of organ tissue sections after an animal model experiment of the traditional Chinese medicine self-assembled nanomaterial prepared in Example 3 of the present invention.

[0044] Figure 6 MRI and relaxation performance diagrams of the traditional Chinese medicine self-assembled nanomaterials prepared in Example 3 of the present invention.

[0045] Figure 7 and Figure 8 This is an MRI image of the traditional Chinese medicine self-assembled nanomaterial prepared in Example 3 of the present invention in an animal model.

[0046] Fig. 9 This is a tumor image of an in situ osteosarcoma animal model treated with the traditional Chinese medicine self-assembled nanomaterial prepared in Example 3 of the present invention.

[0047] Fig.10 a) Particle size distribution diagram and b) appearance in water of the materials prepared in Comparative Examples 1 and 2 of the present invention.

[0048] Fig.11 This is an MRI image of the Chinese medicine granules prepared in Comparative Example 2 of the present invention dissolved in water.

[0049] Fig.12 This is an appearance morphology picture of the material prepared in Comparative Example 3 of the present invention after being heated to room temperature for 48 hours. DETAILED DESCRIPTION

[0050] Hereinafter, embodiments will be described in detail with respect to the traditional Chinese medicine self-assembled nanomaterial and the preparation method and application thereof of the present invention. However, these embodiments are exemplary and the present invention is not limited thereto.

[0051] In one aspect, the present invention provides a traditional Chinese medicine self-assembly nanomaterial, the raw materials for its preparation include mineral traditional Chinese medicine and other traditional Chinese medicine, wherein the other traditional Chinese medicine is one or both of plant-derived traditional Chinese medicine and animal-derived traditional Chinese medicine;

[0052] The traditional Chinese medicine self-assembled nanomaterial has T1-weighted nuclear magnetic resonance imaging function;

[0053] The D50 particle size of the traditional Chinese medicine self-assembled nano material is 30-450nm.

[0054] The raw materials for preparing the traditional Chinese medicine self-assembly nanomaterial are one or two of plant-derived traditional Chinese medicine, animal-derived traditional Chinese medicine and mineral traditional Chinese medicine.

[0055] Botanical Chinese medicine refers to medicines derived from natural plants, mainly roots, stems, leaves, flowers, fruits, seeds and other parts of natural plants. Preferably, the botanical Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis, Herba Polygoni Multiflori, Rhizoma Anemarrhenae, Cortex Phellodendri, Fructus Ligustri Lucidi, Radix Angelicae Sinensis, Salvia miltiorrhizae, Pericarpium Citri Reticulatae, Radix Astragali, and Folium Artemisiae Argyi.

[0056] Animal-derived Chinese medicine is a medicine obtained from an animal or its secretions. Animal-derived Chinese medicine is usually composed of the whole body or certain organs and tissues of a specific species, or excrement and secretions produced by animals. Preferably, the animal-derived Chinese medicine includes but is not limited to one or more of centipede, bezoar, musk, leech, and earthworm.

[0057] Mineral Chinese medicine is a medicine made from natural ores or rocks after processing for medical purposes. Preferably, the mineral Chinese medicine includes one or more of natural copper, ochre, yuyuliang, magnetite, and alum.

[0058] The traditional Chinese medicine self-assembled nanomaterial has a T1-weighted nuclear magnetic resonance imaging function. Further, the traditional Chinese medicine self-assembled nanomaterial has a T1-weighted nuclear magnetic resonance imaging function for tumor tissue.

[0059] There is no restriction on the type of tumor. The tumors described in the popular sense are all within the protection scope of the present invention, and can be benign tumors or malignant tumors. Preferably, the tumors are malignant tumors, including but not limited to osteosarcoma, liver cancer, gastric cancer, breast cancer, prostate cancer, kidney cancer, bladder cancer, lung cancer, colorectal cancer, pancreatic cancer, thyroid cancer, etc. The self-assembled nanomaterials of traditional Chinese medicine can aggregate at the tumor tissue, so that the T1-weighted MRI signal of the tumor tissue is significantly enhanced. The self-assembled nanomaterials of traditional Chinese medicine are expected to accurately distinguish tumor boundaries and normal tissues as nuclear magnetic resonance contrast agents.

[0060] The D50 particle size of the traditional Chinese medicine self-assembled nanomaterial is 30 to 450 nm, and the D50 particle size represents the particle size corresponding to when the cumulative particle size distribution percentage reaches 50%, and is measured by a dynamic light scattering (DLS) method. The measurement method mainly includes: firstly, the nanomaterial is uniformly dispersed in a solvent (such as deionized water, anhydrous ethanol, etc.), the dispersed sample is placed in a dedicated DLS measurement cell, the sample is measured multiple times, and then the data is analyzed and processed by the built-in software to obtain the D50 particle size.

[0061] Preferably, the D50 particle size of the traditional Chinese medicine self-assembled nanomaterial is 50-450 nm, for example, it can be any value among 50, 60, 70, 80, 100, 120, 150, 180, 200, 220, 250, 270, 300, 330, 350, 380, 400, 450 nm, but is not limited to the above values.

[0062] The second aspect of the present invention provides a method for preparing a self-assembled nanomaterial of traditional Chinese medicine, comprising the following steps:

[0063] The mineral Chinese medicine, other Chinese medicines and water are mixed, and then heated for reaction, and then filtered, centrifuged, dialyzed and dried to obtain the Chinese medicine self-assembled nanomaterial;

[0064] The other traditional Chinese medicines are one or both of plant-derived traditional Chinese medicines and animal-derived traditional Chinese medicines.

[0065] Preferably, the plant-derived Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis, Herba speranskiae radix, Rhizoma Anemarrhenae, Phellodendron amurense, Fructus Ligustri Lucidi, Angelica sinensis, Salvia miltiorrhiza, Citrus reticulatae, Astragalus membranaceus, and Artemisia argyi.

[0066] Preferably, the animal-derived Chinese medicine includes, but is not limited to, one or more of centipede, bezoar, musk, leech, and earthworm.

[0067] Preferably, the mineral Chinese medicine includes one or more of natural copper, ochre, Yuyuliang, magnetite, and alum.

[0068] The mineral Chinese medicine and other Chinese medicines can be crushed before use. There is no particular limitation on the crushing size. Generally speaking, the smaller the crushing size within a certain range, the more favorable the reaction is. For example, the crushing size can be ≤1.5 cm.

[0069] Preferably, the mass ratio of the mineral Chinese medicine to other Chinese medicine is 1:0.1 to 1:10, more preferably 1:0.5 to 1:5, for example, 1:0.5, 1:0.7, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5 or 1:5.

[0070] Preferably, the ratio of the mass of water to the total mass of all Chinese medicines is 1 to 100: 1. More preferably, it is 2 to 80: 1, and even more preferably, it is 5 to 50: 1. For example, it can be 5: 1, 8: 1, 10: 1, 15: 1, 20: 1, 25: 1, 30: 1, 35: 1, 40: 1, 45: 1 or 50: 1.

[0071] Preferably, the preparation method further comprises the following steps before the heating reaction: standing for 1 to 60 minutes. Specifically, the mineral Chinese medicine, other Chinese medicines and water are mixed, standing for 1 to 60 minutes, and then heating the mixture.

[0072] Soaking mineral Chinese medicine and other Chinese medicine in water and leaving them to stand for a period of time can help dissolve the active ingredients in the Chinese medicine, save decoction time, and ensure balanced efficacy. The standing time is more preferably 15 to 60 minutes. For example, it can be 15, 18, 20, 25, 30, 35, 40, 45, 50, 55 or 60 minutes.

[0073] Preferably, the temperature of the heating reaction is 70 to 120° C., for example, 70, 80, 85, 88, 90, 93, 95, 97, 100, 110 or 120° C. The heating reaction can be carried out under pressure or normal pressure, such as by pressurizing to a reaction temperature exceeding 100° C. Preferably, the heating reaction is carried out at 80 to 100° C. under normal pressure. Preferably, the heating reaction time is 10 to 200 min, more preferably 20 to 120 min, for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 or 120 min.

[0074] After the heating reaction is completed, filtration is performed. At this time, the pore size of the filter paper used for filtration is ≥1μm, further ≥1.5μm, and further ≥2μm. The pore size of the filter paper should be smaller than the size of the Chinese medicine after crushing. As an example, the pore size of the filter paper can be 1-200μm, and further 1-100μm. The drug residue is effectively removed by filtration to obtain a filtrate containing active ingredients.

[0075] The filtrate obtained by filtration is further centrifuged, and the centrifugation here is preferably gradient centrifugation.

[0076] Preferably, the centrifugation step comprises: performing 2 to 8 centrifugations, the speed of the first centrifugation is 1000 to 7000 rpm, the speed of the subsequent centrifugation is greater than the speed of the previous centrifugation, and the speed of the final centrifugation is 8000 to 15000 rpm; each centrifugation time is 5 to 50 minutes. The time of each centrifugation can be the same or different. After each centrifugation, the supernatant is taken to continue the subsequent operation.

[0077] Through multiple gradient centrifugation, the damage to the activity of the effective ingredients of traditional Chinese medicine can be reduced, the purity of the effective ingredients can be improved, and tiny impurities can be removed.

[0078] For example, four centrifugations are performed, namely the first centrifugation, the second centrifugation, the third centrifugation and the final centrifugation. The speed of the subsequent centrifugation should be greater than the speed of the previous centrifugation, that is, the speed of the second centrifugation should be greater than the speed of the first centrifugation, the speed of the third centrifugation should be greater than the speed of the second centrifugation, and the speed of the final centrifugation should be greater than the speed of the third centrifugation.

[0079] More preferably, the difference between the subsequent centrifugal rotation speed and the previous centrifugal rotation speed is 500 to 6000 rpm.

[0080] More preferably, the centrifugation step comprises: performing 3 to 5 centrifugations, the first centrifugation speed is 2000 to 5000 rpm, the difference between the subsequent centrifugation speed and the previous centrifugation speed is 1000 to 5000 rpm, and the final centrifugation speed is 9000 to 12000 rpm.

[0081] The supernatant obtained from the last centrifugation is placed in a dialysis bag for dialysis. The dialysis is performed in water. The molecular weight cutoff of the dialysis bag is preferably 1000 to 10000 Da, and more preferably 1500 to 8000 Da.

[0082] Preferably, the dialysis time is 10 to 100 hours, more preferably 12 to 72 hours.

[0083] After the dialysis is completed, the solution in the dialysis bag is dried, and the drying can be freeze drying or vacuum drying. Preferably, freeze drying is performed at a temperature of -40 to -100°C, a vacuum degree of 1 to 100 Pa, and a time of 12 to 100 hours.

[0084] The third aspect of the present invention provides the use of the Chinese herbal medicine self-assembled nanomaterial in a nuclear magnetic resonance contrast agent. The Chinese herbal medicine self-assembled nanomaterial has T1-weighted nuclear magnetic resonance imaging function and can be used as a nuclear magnetic resonance contrast agent.

[0085] The fourth aspect of the present invention provides the use of the traditional Chinese medicine self-assembled nanomaterial in drugs for diagnosing and / or treating tumor diseases.

[0086] In the treatment of tumor diseases, the Chinese medicine self-assembled nanomaterial can be used as a nuclear magnetic resonance contrast agent to significantly enhance the T1-weighted MRI signal of tumor tissue, and can accurately distinguish tumor boundaries from normal tissues. In addition, the Chinese medicine self-assembled nanomaterial has the function of generating active oxygen free radicals under acidic conditions, has a killing effect on tumors, and can be used for the treatment of solid tumors.

[0087] Therefore, the traditional Chinese medicine self-assembled nanomaterials can realize the integrated diagnosis and treatment of tumors.

[0088] The technical scheme of the present invention is further described below by specific examples and accompanying drawings. It should be understood that the specific examples described herein are only used to help understand the present invention and are not intended for specific limitations of the present invention. The accompanying drawings used herein are only for better illustrating the disclosure of the present invention and do not have a limiting effect on the scope of protection. If not otherwise specified, the raw materials used in the embodiments of the present invention are all commonly used raw materials in the art, and the methods used in the embodiments are all conventional methods in the art.

[0089] The Chinese medicines used in the following examples and comparative examples were crushed to a size of 0.3-1 mm before use, and the pore size of the filter paper was 2 μm.

[0090] Example 1

[0091] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0092] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0093] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 20 minutes;

[0094] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0095] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0096] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0097] Example 2

[0098] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0099] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0100] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 40 minutes;

[0101] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0102] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0103] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0104] Example 3

[0105] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0106] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0107] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0108] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0109] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0110] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0111] Example 4

[0112] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0113] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0114] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 80 minutes;

[0115] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0116] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0117] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0118] Example 5

[0119] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0120] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0121] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure for 100 minutes;

[0122] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0123] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0124] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0125] Example 6

[0126] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0127] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0128] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure for 120 minutes;

[0129] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0130] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0131] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0132] Example 7

[0133] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0134] (1) After adding 12 g of ochre and 20 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0135] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0136] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0137] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0138] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0139] Example 8

[0140] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0141] (1) After adding 12 g of native copper, 5 g of Yu Yuliang, and 24 g of Cornus officinalis into a reaction container, 200 mL of water was added to soak and allowed to stand for 50 minutes;

[0142] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0143] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0144] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0145] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0146] Example 9

[0147] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0148] (1) After adding 12 g of native copper, 10 g of Cornus officinalis, 14 g of Ligustrum lucidum, and 6 g of Morus alba into a reaction container, 220 mL of water was added to soak and allowed to stand for 30 minutes;

[0149] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0150] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 3000 rpm, 5000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0151] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0152] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 72 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0153] Example 10

[0154] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0155] (1) After adding 6 g of native copper, 6 g of ochre, and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0156] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0157] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 9000 rpm, and 11000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0158] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 30 hours;

[0159] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0160] Embodiment 11

[0161] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0162] (1) After adding 12 g of native copper, 10 g of Cornus officinalis, 5 g of Scolopendra subspinipes, and 5 g of Astragalus membranaceus to a reaction container, 180 mL of water was added to soak and allowed to stand for 30 minutes;

[0163] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0164] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0165] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0166] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0167] Example 12

[0168] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0169] (1) After adding 6 g of native copper, 6 g of ochre, 10 g of Cornus officinalis, and 5 g of centipede into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0170] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0171] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 20 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0172] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 70 hours;

[0173] (5) The solution obtained in (4) is freeze-dried (temperature is -80°C, vacuum degree is 10Pa) for 24 hours to obtain a Chinese medicine self-assembled nanomaterial.

[0174] Embodiment 13

[0175] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0176] (1) After adding 6 g of native copper, 6 g of soap alum, 6 g of Cornus officinalis, 5 g of centipede, and 6 g of Artemisia argyi into a reaction container, 200 mL of water was added to soak and allowed to stand for 20 minutes;

[0177] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0178] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 6000 rpm, 8000 rpm, and 10000 rpm for 40 minutes respectively, and the supernatant was taken from each centrifugation for subsequent centrifugation;

[0179] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 3500 Da dialysis bag and dialyzed in water for 48 hours;

[0180] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 72 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0181] Embodiment 14

[0182] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0183] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0184] (2) heating the solution in (1) to 90 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0185] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 4000 rpm, 8000 rpm, and 10000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0186] (4) The supernatant obtained from the centrifugation step (3) was transferred into an 8000 Da dialysis bag and dialyzed in water for 48 hours;

[0187] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0188] Embodiment 15

[0189] The method for preparing the traditional Chinese medicine self-assembled nanomaterial of this embodiment comprises the following steps:

[0190] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0191] (2) heating the solution in (1) to 95 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0192] (3) After filtering the solution in (2) to remove the residue, the filtrate was subjected to gradient centrifugation at 3000 rpm, 5000 rpm, 7000 rpm, 9000 rpm, and 11000 rpm for 30 minutes respectively, and the supernatant was taken for subsequent centrifugation after each centrifugation;

[0193] (4) The supernatant obtained from the centrifugation step (3) was transferred into a 2000 Da dialysis bag and dialyzed in water for 48 hours;

[0194] (5) The solution obtained in (4) was freeze-dried (temperature: -80°C, vacuum degree: 10Pa) for 48 hours to obtain the Chinese medicine self-assembled nanomaterial.

[0195] The particle size distribution, dispersion and appearance in water of the self-assembled nanomaterials of traditional Chinese medicine obtained in Examples 1 to 6 are as follows: Figure 1 As shown, it can be seen that the traditional Chinese medicine self-assembled nanomaterials have good dispersion in water, and the D50 particle size is between 150 and 350 nm.

[0196] The microscopic morphology of the self-assembled nanomaterials of traditional Chinese medicine obtained in Example 3 is as follows Figure 2 As shown, the D50 particle size is about 190 nm.

[0197] Figure 3 a) is a comparison diagram of the particle size distribution and dispersity of the traditional Chinese medicine self-assembled nanomaterial synthesized 5 times by the method of Example 3. It can be seen that the batch stability of the multiple synthesized batches is high, and the D50 particle size is stable at about 190nm. Figure 3 a) is a comparison diagram of the particle size distribution and dispersity of the self-assembled nanomaterial of traditional Chinese medicine in Example 3 after storage at room temperature for 0, 1, 2, and 3 months. It can be seen that the D50 particle size of the self-assembled nanomaterial of traditional Chinese medicine is still stable at about 190nm after storage at room temperature for 3 months. The room temperature storage stability of the self-assembled nanomaterial of traditional Chinese medicine is high, and the storage time at room temperature can be up to more than 3 months.

[0198] The Chinese medicine self-assembled nanomaterial obtained in Example 3 was dissolved in complete culture medium to prepare solutions of different concentrations. The toxicity results on the normal cell line L929 and the cancer cell lines U2OS and 143B are as follows: Figure 4 As shown, even at a high concentration of 400 μg / mL, the cell viability was above 80%.

[0199] The self-assembled nanomaterials of traditional Chinese medicine obtained in Example 3 were dissolved in PBS to prepare a solution, and 10 mg / kg of the material was injected into the tail vein of 6-week-old Balb / C female mice. The control group was directly injected with PBS. After 14 days of normal feeding after injection, the mice were killed, and the internal organs (heart, liver, spleen, lung, kidney) were taken out, and the tissue sections were observed after HE staining. The results are as follows: Figure 5As shown, there was no lesion in the internal organs compared with normal mice (control group), indicating that the contrast agent has extremely high biosafety.

[0200] The obtained traditional Chinese medicine self-assembled nanomaterials in Example 3 were dissolved in water to prepare solutions with concentrations of 4, 8, 12, 16, and 20 mg / mL. The relaxation properties and MRI imaging properties of the materials were characterized using an MRI imaging system. The results are as follows: Figure 6 As shown in Figure 2, the obtained Chinese medicine self-assembled nanomaterials have good MRI imaging effect and T 1 Relaxation performance;

[0201] The Chinese medicine self-assembled nanomaterial obtained in Example 3 was dissolved in PBS to prepare a solution (concentration of 100 mg / mL). 200 μL of the material was injected into the tail vein of 6-week-old Balb / C Nu female nude mice with established subcutaneous osteosarcoma models. The MRI and metabolic conditions of the animals were observed and recorded within 2 hours after administration. The results are as follows: Figure 7 As shown, by comparing the solid tumor image and its MRI image, it can be seen that the material accumulates significantly in the tumor, which significantly enhances the tumor MRI signal and can be metabolized by the kidneys, and has the potential to be an injected MRI contrast agent.

[0202] The self-assembled nanomaterials of traditional Chinese medicine obtained in Example 3 were dissolved in water to prepare a solution (concentration of 100 mg / mL), and 200 μL of the material was orally administered to normal 6-week-old Balb / C Nu female nude mice by gavage, and the MRI of the animals was observed and recorded within 30 minutes after administration. The results are shown in FIG. Figure 8 As shown, compared with the solution of Example 3 of the same concentration placed in vitro, the MRI signal of the gastrointestinal part of the nude mice increased after oral administration, indicating that Example 3 is rapidly distributed after entering the body and has the potential to be an oral MRI contrast agent.

[0203] The self-assembled nanomaterials of traditional Chinese medicine obtained in Example 3 were dissolved in PBS to prepare a solution. 5 mg / kg of the material was injected into the tail vein of 6-week-old Balb / C Nu female nude mice with established orthotopic osteosarcoma. The control group was directly injected with PBS. The tumor size of the animals was observed and recorded 2 weeks after administration. The results are as follows: Fig. 9 As shown, the contrast images show that tumor growth is inhibited.

[0204] Comparative Example 1

[0205] The difference between Comparative Example 1 and Example 3 is that no other Chinese medicine is added in Comparative Example 1, that is, step (1) of Comparative Example 1 is: adding 12 g of natural copper to a reaction container, adding 150 mL of water to soak and standing for 30 minutes; the subsequent steps (2)-(5) are the same as in Example 3 to obtain Chinese medicine powder particles.

[0206] like Fig.10 As shown, the Chinese medicine powder particles prepared in this comparative example have no particle size after being dissolved in water.

[0207] Comparative Example 2

[0208] The difference between Comparative Example 2 and Example 3 is that no mineral Chinese medicine is added in Comparative Example 2, that is, step (1) of Comparative Example 2 is: adding 15g of Cornus officinalis to a reaction container, adding 150mL of water to soak and standing for 30 minutes; the subsequent steps (2)-(5) are the same as Example 3 to obtain Chinese medicine powder particles.

[0209] The appearance and particle size distribution of the prepared Chinese medicine powder particles dissolved in water are as follows: Fig.10 As shown in the figure, the particles of Chinese medicine powder are nearly micron-sized. Without the addition of mineral Chinese medicine, there is no ion source to become a "seed" as the basis for the assembly of other Chinese medicines, because self-assembled nanomaterials cannot be observed. The nearly micron-sized substances detected here are not nanomaterials self-assembled by small molecules precipitated from Chinese medicine, but may just be fine particles decomposed from the medicinal materials of Cornus officinalis itself.

[0210] The Chinese medicine powder particles obtained in Comparative Example 2 were dissolved in water to prepare solutions with concentrations of 4, 8, 12, 16, and 20 mg / mL. The MRI imaging performance of the material was characterized using an MRI imaging system. The results are as follows: Fig.11 As shown, the signal is similar to that of water and has almost no MRI imaging effect.

[0211] Comparative Example 3

[0212] The difference between Comparative Example 2 and Example 3 is that Comparative Example 3 is not subjected to subsequent treatment. The specific preparation method of Comparative Example 3 is as follows:

[0213] (1) After adding 12 g of native copper and 15 g of Cornus officinalis into a reaction container, 150 mL of water was added to soak and allowed to stand for 30 minutes;

[0214] (2) heating the solution in (1) to 100 degrees Celsius at normal pressure and slightly boiling for 60 minutes;

[0215] (3) After filtering the solution in (2) to remove the residue, the filtrate obtained is the Chinese herbal medicine decoction.

[0216] The Chinese medicine decoction prepared in this comparative example deteriorated and became smelly after only 48 hours at room temperature. Fig.12 shown.

[0217] The various aspects, embodiments, and features of the present invention should be considered to be illustrative in all aspects and not limiting of the present invention, the scope of which is defined solely by the claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.

[0218] In the preparation method of the present invention, the order of each step is not limited to the order listed. For those skilled in the art, without creative work, the order of each step is also within the protection scope of the present invention. In addition, two or more steps or actions can be performed simultaneously.

[0219] Finally, it should be noted that the specific embodiments described herein are merely examples of the present invention, and are not intended to limit the implementation methods of the present invention. A person skilled in the art of the present invention may make various modifications or supplements to the specific embodiments described, or replace them in a similar manner. It is not necessary and impossible to provide all examples of all implementation methods here. However, these obvious changes or modifications derived from the essential spirit of the present invention still fall within the scope of protection of the present invention, and interpreting them as any additional limitation is contrary to the spirit of the present invention.

Claims

1. A Chinese medicine self-assembled nanomaterial, characterized in that: The raw materials for preparing the Chinese medicine self-assembly nanomaterials include mineral Chinese medicines and other Chinese medicines, wherein the other Chinese medicines are one or both of plant-derived Chinese medicines and animal-derived Chinese medicines; The traditional Chinese medicine self-assembled nanomaterial has T1-weighted nuclear magnetic resonance imaging function; The D50 particle size of the traditional Chinese medicine self-assembled nano material is 30-450nm.

2. The Chinese medicine self-assembled nanomaterial according to claim 1, characterized in that: The mineral Chinese medicine is one or more of natural copper, ochre, Yuyuliang, magnetite and alum.

3. The Chinese medicine self-assembled nanomaterial according to claim 1, characterized in that: The plant-based Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis leaves, Herba scutellariae, Rhizoma Anemarrhenae, Phellodendron amurense, Fructus Ligustri Lucidi, Angelica sinensis, Salvia miltiorrhizae, Citrus reticulatae, Astragalus membranaceus and Artemisia 4. The Chinese medicine self-assembled nanomaterial according to claim 1, characterized in that: The animal-derived Chinese medicinal materials are one or more of centipede, bezoar, musk, leech and earthworm.

5. The Chinese medicine self-assembled nanomaterial according to claim 1, characterized in that: The traditional Chinese medicine self-assembled nanomaterial has a T1-weighted magnetic resonance imaging function for tumor tissues; And / or, the D50 particle size of the traditional Chinese medicine self-assembled nanomaterial is 50 to 450 nm.

6. A method for preparing a self-assembled nanomaterial of traditional Chinese medicine, characterized in that: The preparation method comprises the following steps: The mineral Chinese medicine, other Chinese medicines and water are mixed, and then heated for reaction, and then filtered, centrifuged, dialyzed and dried to obtain the Chinese medicine self-assembled nanomaterial; The other traditional Chinese medicines are one or both of plant-derived traditional Chinese medicines and animal-derived traditional Chinese medicines.

7. The preparation method according to claim 6, characterized in that: The mineral Chinese medicine is one or more of natural copper, ochre, Yuyuliang, magnetite, and alum; The botanical Chinese medicine is one or more of Cornus officinalis, Morus alba, Eucommia ulmoides, Dipsacus asper, Platycladus orientalis, Herba scutellariae, Rhizoma Anemarrhenae, Cortex Phellodendri, Fructus Ligustri Lucidi, Angelica sinensis, Salvia miltiorrhizae, Citrus reticulatae, Astragalus membranaceus, and Artemisia arg The animal-derived Chinese medicinal materials are one or more of centipede, bezoar, musk, leech and earthworm.

8. The preparation method according to claim 6, characterized in that: The mass ratio of the mineral Chinese medicine to other Chinese medicines is 1:0.1 to 1:10; And / or, the ratio of the mass of water to the total mass of all Chinese medicines is 1 to 100:

1.

9. The preparation method according to claim 6, characterized in that: The preparation method further comprises the following steps before the heating reaction: standing for 1 to 60 minutes.

10. The preparation method according to claim 6, characterized in that: The temperature of the heating reaction is 70 to 120° C., and the time of the heating reaction is 10 to 200 minutes.

11. The preparation method according to claim 6, characterized in that: The centrifugation step includes: performing 2 to 8 centrifugations, the first centrifugation speed is 1000 to 7000 rpm, the subsequent centrifugation speed is greater than the previous centrifugation speed, and the final centrifugation speed is 8000 to 15000 rpm; each centrifugation time is 5 to 50 minutes.

12. The preparation method according to claim 11, characterized in that: The difference between the subsequent centrifugal rotation speed and the previous centrifugal rotation speed is 500 to 6000 rpm.

13. The preparation method according to claim 6 or 11, characterized in that: The centrifugation step includes: performing 3 to 5 centrifugations, the first centrifugation speed is 2000 to 5000 rpm, the difference between the subsequent centrifugation speed and the previous centrifugation speed is 1000 to 5000 rpm, and the final centrifugation speed is 9000 to 12000 rpm.

14. The preparation method according to claim 6, characterized in that: The supernatant obtained by centrifugation is placed in a dialysis bag for dialysis, the molecular weight cutoff of the dialysis bag is 1000-10000Da, and the dialysis time is 10-100h.

15. The preparation method according to claim 6, characterized in that: The drying is freeze drying or vacuum drying; The freeze-drying temperature is -40 to -100°C, the vacuum degree is 1 to 100 Pa, and the time is 12 to 100 hours.

16. Use of the Chinese medicinal self-assembled nanomaterial as claimed in claim 1 or the Chinese medicinal self-assembled nanomaterial prepared by the preparation method as claimed in claim 6 in nuclear magnetic resonance contrast agents.

17. Use of the Chinese medicinal self-assembled nanomaterial as claimed in claim 1 or the Chinese medicinal self-assembled nanomaterial prepared by the preparation method as claimed in claim 6 in drugs for diagnosing and / or treating tumor diseases.

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