Matrine-natural polyphenol amorphous substance as well as preparation method and application thereof

Abstract

The invention provides a matrine-natural polyphenol amorphous substance as well as a preparation method and application thereof, and relates to the technical field of polyphenol and alkaloid pharmacy, in the matrine-natural polyphenol amorphous substance, the molar ratio of matrine to natural polyphenol is (1-2): (1-2), through strong interaction between matrine and polyphenol substances, the matrine-natural polyphenol amorphous substance can be used for preparing the natural polyphenol, and the matrine-natural polyphenol amorphous substance can be used for preparing the natural polyphenol. The physicochemical properties of the medicine in the amorphous substance, such as solubility, polarity and lipid-water partition coefficient, are changed, the slow release of the medicine is realized, and the IC50 value of the amorphous substance is reduced; in addition, matrine and polyphenol substances exert synergistic anti-oxidative stress capability, the ROS (reactive oxygen species) level of cells is reduced, and the toxicity of natural polyphenols to the cells is further reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of polyphenols and alkaloids, and specifically relates to a matrine-natural polyphenol amorphous substance and a preparation method and application thereof. Background Art

[0002] Natural polyphenols such as quercetin, curcumin, and resveratrol have multiple biological activities such as anti-inflammatory, anti-cancer, antioxidant, and cardiovascular protection, and are easy to obtain and abundant; therefore, polyphenol compounds are increasingly used in dietary supplements or health foods. Polyphenols are also found in daily diets, such as fruits and vegetables, nuts, soybeans, tea, cocoa, and alcohol. However, studies have shown that excessive intake of flavonoids has potential genetic toxicity and mutagenicity. If the intake of polyphenols is too high, the toxicity of polyphenols will increase, which will cause greater harm to normal cells, thus limiting the clinical application of such substances. Summary of the invention

[0003] In view of this, the present invention provides a matrine-natural polyphenol amorphous material to reduce the toxicity of natural polyphenols and improve the application range thereof.

[0004] It is also necessary to provide a method for preparing amorphous matrine-natural polyphenols.

[0005] It is also necessary to provide an application of matrine-natural polyphenol amorphous material.

[0006] The technical solution adopted by the present invention to solve its technical problem is: A matrine-natural polyphenol amorphous material, wherein the molar ratio of matrine to natural polyphenol is 1-2:1-2.

[0007] Preferably, the natural polyphenol is selected from one of quercetin, resveratrol, curcumin, hesperetin, apigenin, myricetin, naringenin, baicalein, catechin and isoliquiritigenin.

[0008] The method for preparing the above-mentioned matrine-natural polyphenol amorphous material comprises the following steps: S1: adding matrine and natural polyphenols into a solvent and stirring at room temperature to obtain a first mixture; S2: rotary evaporating the first mixture to dryness to obtain a crude product of matrine-natural polyphenol amorphous substance; S3: vacuum drying the crude product of matrine-natural polyphenols amorphous substance to obtain matrine-natural polyphenols amorphous substance.

[0009] Preferably, in S1, the solvent is one or two of methanol, ethanol, ethyl acetate, acetone and tetrahydrofuran.

[0010] Preferably, in S1, stirring is performed at room temperature for 5 h to 8 h.

[0011] Preferably, in S2, the temperature of the rotary evaporation is 45°C-55°C.

[0012] Preferably, in S3, the vacuum drying temperature is 35°C-45°C.

[0013] The matrine-natural polyphenol amorphous material as described above can be used as a new drug dosage form in the preparation of colitis or hepatitis drugs or tumors.

[0014] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a matrine-natural polyphenol amorphous material, wherein the molar ratio of matrine to natural polyphenol is 1-2:1-2, and through the strong interaction between matrine and polyphenols, the physicochemical properties of the drug in the amorphous material, such as solubility, polarity, and lipid-water partition coefficient, are changed, and the sustained release of the drug is achieved. The IC 50 In addition, matrine and polyphenols exert synergistic antioxidant stress resistance, reducing cellular ROS levels and thus playing a detoxifying role.

[0015] The present invention provides a method for preparing a matrine-natural polyphenol amorphous material, which is prepared by a solvent evaporation method and requires a small amount of sample. During the preparation process, a crystalline drug or an excipient is first dissolved in a solvent, and then the solvent is quickly evaporated and the remaining solid is precipitated to form a co-amorphous preparation. The preparation method is simple and convenient.

[0016] The matrine-natural polyphenol amorphous material provided by the invention has low toxicity, good sustained release and solubility, and thus has high bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 DSC graphs of matrine, resveratrol, matrine-resveratrol amorphous substance and mixture.

[0018] Figure 2 These are the DSC graphs of matrine, quercetin, matrine-quercetin amorphous substance and mixture.

[0019] Figure 3 These are the DSC graphs of matrine, curcumin, matrine-curcumin amorphous substance and mixture.

[0020] Figure 4 This is a DSC comparison chart of resveratrol.

[0021] Figure 5 This is a DSC comparison chart of quercetin.

[0022] Figure 6This is a DSC comparison chart of curcumin.

[0023] Figure 7 PXRD patterns of matrine, resveratrol, matrine-resveratrol amorphous substance and mixture.

[0024] Figure 8 PXRD patterns of matrine, quercetin, matrine-quercetin amorphous and mixture.

[0025] Fig. 9 PXRD patterns of matrine, curcumin, matrine-curcumin amorphous substance and mixture.

[0026] Fig.10 This is a PXRD comparison diagram of resveratrol.

[0027] Fig.11 This is a PXRD comparison diagram of quercetin.

[0028] Fig.12 This is a PXRD comparison diagram of curcumin.

[0029] Fig.13 These are infrared images of matrine, resveratrol, matrine-resveratrol amorphous substance, and mixture.

[0030] Fig.14 These are infrared images of matrine, quercetin, matrine-quercetin amorphous and mixture.

[0031] Fig.15 These are infrared images of matrine, curcumin, matrine-curcumin amorphous substance and mixture.

[0032] Fig.16 This is the van der Waals force penetration diagram between matrine and resveratrol molecules.

[0033] Fig.17 This is the van der Waals force penetration diagram between matrine and quercetin molecules.

[0034] Fig.18 This is the van der Waals force penetration diagram between matrine and curcumin molecules (Note: cyan atoms represent carbon atoms, red atoms represent oxygen atoms, purple atoms represent nitrogen atoms, and white atoms represent hydrogen atoms).

[0035] Fig.19 This is a diagram showing the powder dissolution characteristics of resveratrol.

[0036] Fig. 20 This is a diagram showing the powder dissolution characteristics of quercetin.

[0037] Fig.21 This is a diagram of the powder dissolution characteristics of curcumin (Note: the concentration of curcumin is too small to be detected by UV).

[0038] Fig. 22 The graph shows the cytotoxicity results of polyphenol amorphous substances and the corresponding physical mixtures.

[0039] Fig.23 Matrine cytotoxicity graph.

[0040] In the figure: Fig.13 in (a)Mat; (b)Res; (c)Mat:Res (1:1); (d)Mat:Res (1:1)PM; Fig.14 in (a)Mat; (b)Que; (c)Mat:Que (1:1); (d)Mat:Que (1:1)PM; Fig.15 In (a)Mat; (b)Cur; (c)Mat:Cur (1:1); (d)Mat:Cur (1:1)PM. DETAILED DESCRIPTION

[0041] The technical solutions and technical effects of the embodiments of the present invention are further described in detail below in conjunction with the accompanying drawings of the present invention.

[0042] A matrine-natural polyphenol amorphous material, wherein the molar ratio of matrine to natural polyphenol is 1-2:1-2.

[0043] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a matrine-natural polyphenol amorphous material, wherein the molar ratio of matrine to natural polyphenol in the matrine-natural polyphenol amorphous material is 1-2:1-2, and through the strong interaction between matrine and polyphenol substances, the physicochemical properties of the drug in the amorphous material, such as solubility, polarity, and lipid-water partition coefficient, are changed, and the sustained release of the drug is achieved. The IC 50 In addition, matrine and polyphenols exert synergistic antioxidant stress resistance, reducing cellular ROS levels and thus playing a detoxifying role.

[0044] Furthermore, the natural polyphenol is selected from one of quercetin, resveratrol, curcumin, hesperetin, apigenin, myricetin, naringenin, baicalein, catechin and isoliquiritigenin.

[0045] The method for preparing the above-mentioned matrine-natural polyphenol amorphous material comprises the following steps: S1: adding matrine and natural polyphenols into a solvent and stirring at room temperature to obtain a first mixture to dissolve the raw materials; S2: rotary evaporating the first mixture to dryness to obtain a crude product of matrine-natural polyphenol amorphous material, and rotary evaporating to remove the solvent; S3: vacuum drying the crude matrine-natural polyphenol amorphous substance to fully remove the remaining residual solvent to obtain the matrine-natural polyphenol amorphous substance.

[0046] Furthermore, in S1, the solvent is one or two of methanol, ethanol, ethyl acetate, acetone, and tetrahydrofuran, so that the raw material can be dissolved and easily removed by rotary evaporation.

[0047] Furthermore, in S1, stirring is performed at room temperature for 5-8 h. If the stirring time is too short, the reaction will be incomplete; if the stirring time is too long, the polyphenols will be easily oxidized and degraded.

[0048] Furthermore, in S2, the temperature of the rotary evaporation is 45-55°C to prevent the solution from boiling violently due to the high temperature.

[0049] Furthermore, in S3, the vacuum drying temperature is 35 - 40 °C.

[0050] The matrine-natural polyphenol amorphous material as described above can be used as a new drug dosage form in the preparation of hepatitis, colitis or tumor drugs.

[0051] Furthermore, the tumor refers to one of colon cancer, liver cancer, and cervical cancer.

[0052] The use of the present invention is described by the following examples.

[0053] 1. Sample preparation Embodiment 1:

[0054] Preparation of Matrine-Resveratrol (Mat-Res) Amorphous Compound: 1.1. Weigh 1.00 g of resveratrol (4.38 mmol) and 1.09 g of matrine (4.39 mmol) and add them to 20.0 mL of methanol. Stir at room temperature for 6 h. Use a rotary evaporator to evaporate to dryness at about 50 °C. Then vacuum dry the obtained sample at 40 °C overnight to remove the residual solvent. Dry and obtain a matrine-resveratrol (1:1) sample, which is sealed and stored.

[0055] 1.2. Weigh 0.10 g resveratrol (0.44 mmol) and 0.06 g matrine (0.24 mmol). Other steps are the same as those in 1.1. Dry to obtain a matrine-resveratrol (1:2) sample and seal it for storage.

[0056] 1.3. Weigh 0.23 g resveratrol (1.01 mmol) and 0.50 g matrine (2.01 mmol). The other conditions are the same as those in 1.1. The liquid is not dried during rotary evaporation. No amorphous material is formed at this ratio.

[0057] 1.4. Preparation of matrine-resveratrol physical mixture: Matrine and resveratrol were uniformly mixed at a matrine to resveratrol molar ratio of 1:1 and 1:2, respectively, to obtain Mat-Res (1:1) PM and Mat-Res (1:2) PM. Embodiment 2:

[0058] Preparation of Matrine-Quercetin (Mat-Que) Amorphous Compound: 2.1. Weigh 0.10 g quercetin (0.33 mmol) and 0.08 g matrine (0.32 mmol). Other steps are the same as those in 1.1. Dry the mixture to obtain a matrine-quercetin (1:1) sample and seal it for storage.

[0059] 2.2. Weigh 0.10 g quercetin (0.33 mmol) and 0.04 g matrine (0.16 mmol). Other steps are the same as in 1.1. Dry to obtain a matrine-quercetin (1:2) sample and seal it for storage.

[0060] 2.3. Weigh 0.10 g quercetin (0.33 mmol) and 0.16 g matrine (0.64 mmol). Other steps are the same as in 1.1. Dry to obtain a matrine-quercetin (2:1) sample and seal it for storage.

[0061] 2.4. Preparation of matrine-quercetin physical mixture: Matrine and quercetin were uniformly mixed at a molar ratio of matrine to quercetin of 1:1, 1:2 and 2:1 to obtain Mat-Que (1:1) PM, Mat-Que (1:2) PM and Mat-Que (2:1) PM. Embodiment 3:

[0062] Preparation of Matrine-Curcumin (Mat-Cur) Amorphous 3.1. Weigh 0.10 g curcumin (0.27 mmol) and 0.07 g matrine (0.28 mmol). Other steps are the same as those in 1.1. Dry to obtain a matrine-curcumin (1:1) sample and seal it for storage.

[0063] 3.2. Weigh 0.20 g curcumin (0.54 mmol) and 0.08 g matrine (0.28 mmol). Other steps are the same as those in 1.1. Dry to obtain a matrine-curcumin (1:2) sample and seal it for storage.

[0064] 3.3. Weigh 0.22 g curcumin (0.60 mmol) and 0.3 g matrine (1.21 mmol). Other steps are the same as in 1.1. Dry to obtain a matrine-curcumin (2:1) sample and seal it for storage.

[0065] 3.4. Preparation of matrine-curcumin physical mixture: Matrine and curcumin were uniformly mixed at a molar ratio of matrine to curcumin of 1:1, 1:2 and 2:1, respectively, to obtain Mat-Cur (1:1) PM, Mat-Cur (1:2) PM and Mat-Cur (2:1) PM.

[0066] 2. Sample Characterization 1. Solid-state characterization (1) Differential scanning calorimetry (DSC) Matrine (Mat), natural polyphenols (Res, Que, Cur), amorphous substances prepared in Examples 1 to 3, and corresponding physical mixtures, each weighing 3 to 4 mg, were placed in an aluminum crucible and then analyzed using a DSC (MettlerToledo, Switzerland) synchronous thermal analyzer. The heating rate was 10 °C min - 1 , the measurement range is 25 - 300 ° C. Origin 2017 software was used to analyze the glass transition temperature (Tg), melting point (Tm, endothermic peak) and recrystallization peak (Tr, exothermic peak).

[0067] (2) Powder X-ray diffraction (PXRD) Mat, natural polyphenols (Res, Que, Cur), amorphous materials prepared in Examples 1-3, and the corresponding physical mixtures were sieved through a 100-mesh sieve, and about 100 mg of each sample was taken for further analysis. The samples were measured at room temperature using an AdvanceD8 X-ray diffractometer (Bruker, Germany), with a 2θ rotation range of 5-100° and a scanning speed of 10°min - 1 The data were analyzed using Origin 2017 software.

[0068] (3) Fourier transform infrared spectroscopy (FTIR) Mat, natural polyphenols (Res, Que, Cur), the amorphous substances prepared in Examples 1 to 3, and the physical mixtures of the corresponding physical mixtures and KBr were pressed into thin sheets. Infrared spectra were measured using a Tensor 27 Fourier transform infrared spectrometer from Bruker, Germany, at 4000 - 400 cm −1 The spectrum was obtained by scanning 64 times in the range. The resolution of the instrument is 8 cm -1 . IR spectra were recorded using OPUS software. Data analysis was performed using Origin 2017 software.

[0069] 2. Computer simulation APIs and API-ILs were simulated using Gaussian 16 software, Multiwfn [1] and VMD [2]. First, single molecules of three polyphenols and matrine and two molecular combinations of three amorphous substances were calculated based on the Custom / 6-31G(d) / m062x method (Gaussian 16) to optimize the ground state molecular structure and frequency, and further Multiwfn and VMD programs were used to draw intermolecular van der Waals force penetration maps.

[0070] 3. Powder supersaturated dissolution test Powder dissolution characteristics of crystalline Mat, natural polyphenols (crystalline Res, crystalline Que, crystalline Cur), matrine-natural polyphenol physical mixture (PM) and amorphous materials at the same proportion in pH 6.8 PBS. Taking resveratrol amorphous material as an example, Mat, Res, Mat-Res physical mixture, and co-amorphous Mat-Res powder were weighed and added into a glass container containing 20mL pH 6.8 PBS at 37°C and stirring speed of 100 rpm. At the predetermined time (5, 10, 20, 30, 40, 60min), an appropriate amount of solution was taken out, filtered through a 0.22 μm filter, and the same volume of fresh dissolution medium was added. Analyzed by UV spectroscopy.

[0071] 4. Cytotoxicity Normal human liver cells L02 (Saibokang Shanghai Biotechnology Co., Ltd.) were cultured in 1640 medium (Wuhan Seville Biotechnology Co., Ltd.) supplemented with 10% fetal bovine serum (Wuhan Seville Biotechnology Co., Ltd.) and 1% triple antibody (Wuhan Seville Biotechnology Co., Ltd.). The samples were completely dissolved in 1640 medium and diluted to different concentrations. Logarithmically growing cells (L02) were seeded in 96-well plates at a density of 1105 cells / well and incubated at 37°C, 5% CO2 atmosphere for 24 h. The culture medium in the wells was replaced with the sample solution, and clean culture medium was used as a control. After incubation for 24 h, CCK-8 solution (100 μL) was added to each well and incubated for 1 h. The optical density (OD) at 450 nm was measured using a Bio-Tek Gen 5 microplate reader. The cell inhibition rate (%) of each group was calculated using formula (1) and the cell viability was calculated as follows: A control, A sample and A blank are the OD values ​​of the control, sample solution and cell-free well. For the three amorphous substances and physical mixtures, the medium was 1640 medium dissolved in 1% (v / v) DMSO. The experiment was performed in triplicate and the sample data were analyzed using GraphPad Prism 8.0 to determine the IC 50 The cytotoxicity of matrine (2 mg / mL, 4 mg / mL, 6 mg / mL), three amorphous forms and their physical mixtures (1 mg / mL, 3 mg / mL, 5 mg / mL) on normal human hepatocytes (L02) for 24 h was studied, with the physical mixture as the positive control group.

[0072] 3. Results and Analysis 1. From DSC Figure 1 and Figure 4 It can be seen that the Tg of the sample Mat: Res (1:1) is 193 ℃, which is between the melting points of matrine and resveratrol. There are no endothermic peaks of matrine and resveratrol in the DSC graph, which is not a simple superposition of the two. However, in the DSC graph of the physical mixture Mat: Res (1:1) PM with the same proportion, the endothermic peaks of matrine appear at 73 ℃ and 88 ℃, and there is a new peak at 199 ℃, indicating that the two molecules in the physical mixture may form a new system, proving that Mat-Res (1:1) forms a uniform amorphous system. Surprisingly, in the DSC graph of the physical mixture Mat: Res (1:2) PM, there is no peak related to matrine, and there is a blunt peak between 200-225 ℃, and no amorphous system is generated.

[0073] From DSC Figure 2 and Figure 5It can be seen that for the samples formed under the three ratio conditions, the DSC graph of sample Mat: Que (1:1) has a single Tg of 62 °C, and no relevant peaks of matrine and quercetin appear, which is obviously different from the DSC graph of the physical mixture under the same ratio, proving that a uniform amorphous system is formed; while the DSC graphs of samples Mat: Que (1:2) and Mat: Que (2:1) both have the endothermic peak of matrine and the exothermic peak of quercetin, and there are two other exothermic peaks of 170 °C and 240 °C in sample Mat: Que (1:2), and no amorphous system is generated.

[0074] From DSC Figure 3 and Figure 6 It can be seen that in the matrine-curcumin system, the DSC graphs of the physical mixture Mat: Cur (1:1)PM and the physical mixture Mat: Cur (1:2)PM are similar, and both have a matrine endothermic peak of 76 °C; the sample Mat: Cur (1:1) has a Tg of 52 °C, but the sample Mat: Cur (1:2) has an endothermic peak at 53 °C, so the sample Mat: Cur (1:1) is an amorphous substance.

[0075] 2. According to DSC Figures 1 to 6 It can be seen that when the molar ratio of matrine to natural polyphenols is 1:1, amorphous substances can be formed. Therefore, the physical mixture of matrine-natural polyphenols (1:1) and the rotary evaporation vacuum dried samples of matrine-natural polyphenols (1:1) were subjected to X-ray diffraction. The PXRD patterns are shown in Figure 7-12The crystals show characteristic peaks, such as crystal matrine has characteristic peaks at 12.37, 14.57, 17.09, 20.36, 23.55 (2θ); crystal resveratrol has characteristic peaks at 6.59, 10.11, 13.30, 16.37, 19.27, 22.36, 23.66, 28.18 (2θ); crystal quercetin has characteristic peaks at 10.6 There are characteristic peaks at 0, 13.03, 14.02, 16.78, 24.07, 26.37, 27.36, and 28.18 (2θ); there are characteristic peaks at 8.66, 12.21, 14.51, 17.02, 18.01, 21.10, 23.20, 24.52, 27.36, 28.80, and 34.32 for crystalline curcumin. At the same time, characteristic peaks still appear in the PXRD patterns of Mat: Res (1:1) PM, Mat: Que (1:1) PM, and Mat: Cur (1:1) PM. For example, in Mat: Res (1:1) PM, it is 6.75, 7.10, 11.73, 14.18, 16.78, 19.27, 23.16, 28.22 (2θ), and the characteristic peak of crystalline resveratrol 19.27 appears; in Mat: Que (1:1) PM, it is 7.02, 11.59, 16.61, 19.82, 22.67, 26.41, 29.91, 44.37 (2θ); in Mat: Cur (1:1) PM, it is 7.02, 8.83, 11.63, 13.94, 16.53, 17.19, 18.59, 19.87, 23.00, 27.90, 31.48, 41.40. The appearance of these characteristic peaks indicates that there are still crystals in the physical mixture of matrine-natural polyphenols (1:1); and the PXRD pattern of the matrine-natural polyphenols (1:1) rotary evaporation vacuum dried sample shows a typical halo, without the characteristic peaks of matrine or natural polyphenols, indicating that the three matrine-natural polyphenols (1:1) rotary evaporation vacuum dried samples are amorphous, which is mutually verified with the DSC results.

[0076] 3. Through infrared detection results Figure 13-15 It can be seen that the characteristic peak of hydroxyl groups in natural polyphenol molecules is at 3500 cm -1 There are obvious absorption peaks, and the three matrine-natural polyphenols (1:1) have an absorption peak at 3500 cm -1 The absorption peak of hydroxyl group becomes broad and blunt or almost indistinct, which proves the existence of hydrogen bond in amorphous substance; while the corresponding physical mixture is a simple superposition of infrared absorption peaks of two molecules. Combining infrared and computer simulation ( Fig.16 - 18), it can be inferred that there are hydrogen bonds, van der Waals forces and other interactions between matrine and polyphenols.

[0077] 4. Powder supersaturated dissolution test from Fig.19 It can be seen that the amorphous form of Res increases the solubility of monomeric Res and exhibits a burst release effect. The maximum concentration of the amorphous group at 5 min is 76.98 μg / mL, which is much greater than 30.92 μg / mL (physical mixture group) and 6.18 μg / mL (crystalline resveratrol group); the final concentration of amorphous Res is comparable to that of the physical mixture, both of which are higher than that of monomeric Res, indicating that there is an interaction between matrine and resveratrol molecules in the solution, which increases the solubility of resveratrol. Fig. 20 It can be seen that the amorphous form of Que has little effect on the solubility of Que, but it shows a burst release effect. At 5 min, the maximum concentration of the amorphous group was 16.82 μg / mL, and the physical mixture group was 18.36 μg / mL, both higher than the monomer 7.14 μg / mL. The final concentration of Que amorphous was equivalent to that of the physical mixture and monomer, indicating that there was an interaction between matrine and quercetin molecules in the solution, but it had little effect on the solubility of quercetin. Fig.21 It can be seen that the solubility of curcumin amorphous and physical mixtures is very different, resulting in the failure to detect curcumin by UV spectrophotometer under normal conditions, indicating that there are different interactions between curcumin and matrine molecules.

[0078] The above dissolution experiments show that polyphenols of different structural types form amorphous substances with matrine, which have different effects on their solubility. There may be different forces between molecules with different intensities.

[0079] 5. Cytotoxicity Assay Table 1 Summary of cytotoxicity of polyphenols

[0080] Depend on Fig.19 , 20 It can be seen that under the three concentration conditions, the cell inhibition rate of 3 mg / mL and 5 mg / mL is close to 100%. At a concentration of 1 mg / mL, the cytotoxicity of amorphous resveratrol and amorphous quercetin is less than that of the corresponding physical mixture; while there is no significant difference in the cytotoxicity of amorphous curcumin and its physical mixture. In addition, in the present invention, the amorphous can reduce the cytotoxicity of polyphenols. The IC 50 The value is about 1 mg / mL, and the IC of quercetin amorphous 50 The value is slightly less than 1 mg / mL. The cytotoxicity of polyphenols has been reported in the literature and is summarized in Table 1. It can be seen from the table that the IC50 The value is at the concentration μg / mL level, which is much smaller than the IC 50 value (1 mg / mL), it can be concluded that making natural polyphenols into amorphous substances can reduce toxicity. The reason may be that through the interaction between matrine and polyphenols, the physicochemical properties of the drug in the amorphous substance, such as the lipid-water partition coefficient, change, and achieve sustained release of the drug, reducing cellular uptake, and the IC of the amorphous substance 50 In addition, matrine and polyphenols exert synergistic antioxidant stress resistance, reducing cellular ROS levels and thus playing a detoxifying role.

[0081] The current literature list is as follows: 1. L. Tian, ​​C. Feiwu, J. Comput. Chem., 2022, 33, 580-592. 2. W. Humphrey, A. Dalke, K. Schulten. "VMD - Visual MolecularDynamics" J. Molec.Graphics 1996,14(1):33-38. 3. Liu Bin, Xu Ke, Han Hongbin, et al. Experimental study on apoptosis of A549 cells induced by resveratrol[J]. Chinese Journal of Oncology Prevention and Treatment, 2014, 21(10): 740-743. 4. Li Wangping, Ma Lijie, Pan Lei, et al. Study on the mechanism of resveratrol-induced apoptosis of small cell lung cancer H446 cells[J]. Chinese Journal of Lung Diseases (Electronic Edition), 2019, 12(01): 15-23. 5. Wang Yaowen, Zhang Xueqiong, Ma Jingjing, et al. Application of resveratrol nanoparticles prepared based on PEG-PLGA and CMCS carriers in the treatment of colon cancer[J]. World Science and Technology-Modernization of Traditional Chinese Medicine, 2019, 21(09): 1924-1931. 6. Miao Fang, Ma Lan. Study on in vitro stability and hepatocellular carcinoma cell toxicity of quercetin lipid nanoparticle freeze-dried powder[J]. Drug Evaluation, 2022, 19(08): 449-453. 7. Xu Hao, Gao Yixuan, Wang Xiangtao. Preparation, characterization and anti-breast cancer research of quercetin nanosuspension[J]. Chinese Herbal Medicine, 2019, 50(01): 42-51. 8. Cao Jun, Jiang Liping, Geng Chengyan, et al. Role of reactive oxygen species in the cytotoxicity of curcumin on human embryonic kidney 293 cells[J]. Journal of Toxicology, 2009, 23(04): 260-263. 9. Jia Shujie, Liu Qinghuan, Wang Wentong, et al. Preparation of curcumin, demethoxycurcumin and bisdemethoxycurcumin reference substances and preliminary study on curcumin cytotoxicity[J]. Chinese Herbal Medicine, 2012, 43(06): 1118-1121. 10. He Yuan, Zhang Yarong, Li Qiuxia, et al. Preparation and preliminary cytotoxicity study of hyaluronic acid modified curcumin chitosan nanoparticles[J]. Chinese Journal of Pharmaceutical Industry, 2015, 46(02): 162-167. 11. Meng Luhua, Zhao Yi, Pan Lijun, et al. Preparation and cytotoxicity study of vitamin A-curcumin liposomes[J]. Chinese Journal of Pharmaceutical Sciences, 2011, 46(14): 1104-1107. What is disclosed above is only a preferred embodiment of the present invention, which certainly cannot be used to limit the scope of rights of the present invention. A person skilled in the art can understand that all or part of the processes of the above embodiments and equivalent changes made according to the claims of the present invention still fall within the scope of the invention.

Claims

1. A matrine-natural polyphenol amorphous substance, characterized in that: The molar ratio of matrine to natural polyphenols in the matrine-natural polyphenol amorphous material is 1-2:1-2.

2. The amorphous material of matrine-natural polyphenols according to claim 1, characterized in that: The compound is one selected from quercetin, resveratrol, curcumin, hesperetin, apigenin, myricetin, naringenin, baicalein, catechin and isoliquiritigenin.

3. The method for preparing the matrine-natural polyphenol amorphous material according to claim 1, characterized in that: The following steps are involved: S1: adding matrine and natural polyphenols into a solvent and stirring at room temperature to obtain a first mixture; S2: rotary evaporating the first mixture to dryness to obtain a crude product of matrine-natural polyphenol amorphous substance; S3: vacuum drying the crude product of matrine-natural polyphenols amorphous substance to obtain matrine-natural polyphenols amorphous substance.

4. The method for preparing the amorphous matrine-natural polyphenols according to claim 3, characterized in that: In S1, the solvent is one or two of methanol, ethanol, ethyl acetate, acetone, and tetrahydrofuran.

5. The method for preparing the matrine-natural polyphenol amorphous material according to claim 3, characterized in that: In S1, the mixture was stirred at room temperature for 5 h-8 h.

6. The method for preparing the amorphous matrine-natural polyphenols according to claim 3, characterized in that: In S2, the temperature of the rotary evaporation is 45°C-55°C.

7. The method for preparing the amorphous matrine-natural polyphenols according to claim 3, characterized in that: In S3, the vacuum drying temperature is 35°C-45°C.

8. Use of the matrine-natural polyphenol amorphous substance as claimed in claim 1 or 3 in the preparation of colitis, hepatitis or tumor drugs.

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