Sodium aescinate-hydroxysafflor yellow A hydrogel, preparation method and application of sodium aescinate-hydroxysafflor yellow A hydrogel in sepsis

Abstract

The invention discloses sodium aescinate-hydroxysafflor yellow A hydrogel as well as a preparation method and application of the hydrogel in sepsis. The invention provides the preparation method of the sodium aescinate-hydroxysafflor yellow A hydrogel, the preparation method is simple, convenient and stable, and the injectable sodium aescinate-hydroxysafflor yellow A hydrogel with high stability can be prepared. The sodium aescinate-hydroxysafflor yellow A hydrogel has a remarkable treatment effect on sepsis of mice; the sodium aescinate and the hydroxysafflor yellow A used as the raw materials of the sodium aescinate-hydroxysafflor yellow A hydrogel are natural products, other auxiliary materials or complex reagents, catalysts and the like do not need to be added, and the sodium aescinate-hydroxysafflor yellow A hydrogel is high in safety, good in biocompatibility and biodegradable.

Description

Technical Field

[0001] The invention relates to preparation and application of a hydrogel, and in particular to a sodium aescinate-hydroxysafflor yellow A hydrogel, a preparation method and application of the hydrogel in sepsis. Background Art

[0002] Sepsis is a systemic inflammatory response syndrome caused by infection. It is an imbalance of the body's immune response caused by bacterial, viral, fungal or parasitic infections, resulting in vascular endothelial damage, microcirculatory disorders and tissue hypoxia, which in turn leads to multiple organ dysfunction and even failure. It is one of the leading causes of death in intensive care unit (ICU) patients worldwide. Sepsis usually progresses rapidly, and if not intervened in time, it may deteriorate into severe sepsis or septic shock, the latter of which is accompanied by persistent hypotension and has a very high mortality rate. The main treatment options currently used include early use of antibiotics, supportive therapy, fluid resuscitation, etc.

[0003] Safflower, also known as saffron and saffron, can be used as a traditional Chinese medicine with its dried tubular flowers. It has the effects of promoting blood circulation, removing blood stasis and relieving pain, and is widely planted in my country. Safflower petals contain a variety of active ingredients, among which the representative quality marker Hydroxysafflor Yellow A (HSYA) belongs to the flavonoids. The molecule contains multiple hydrogen bonds and unsaturated double bonds. It can achieve antioxidant effects by scavenging free radicals and inhibiting lipid peroxidation, inhibiting the release of inflammatory mediators and regulating related signal pathways to achieve anti-inflammatory effects. It has potential in the use of drug delivery systems (such as hydrogels, nanoparticles, etc.) to treat cardiovascular and cerebrovascular diseases, arthritis and other diseases.

[0004] At present, there is no report on the preparation of hydroxysafflor yellow A into hydrogel in the prior art, let alone the preparation of injectable hydrogel. In the prior art, injectable hydrogels are mainly administered locally in situ using polymers such as biopolysaccharides. There are relatively few hydrogels that can be injected intravenously without blocking blood vessels. Currently, there are reports of supramolecular hydrogels composed of nanoparticles, liposomes, polypeptides, etc., and there is almost no research on tail vein injection.

[0005] The applicant invented a hydrogel for treating sepsis and proposed the present invention. Summary of the invention

[0006] The first purpose of the present invention is to provide a method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel, the second purpose is to provide sodium aescinate-hydroxysafflor yellow A hydrogel prepared by the preparation method, and the third purpose is to provide an application of the hydrogel in the preparation of a drug for treating sepsis.

[0007] The above-mentioned purpose of the present invention is achieved through the following technical solutions: A method for preparing a sodium aescinate-hydroxysafflor yellow A hydrogel comprises the following steps: directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution for self-assembly to form a hydrogel; or firstly dissolving sodium aescinate and hydroxysafflor yellow A in an organic solvent and then removing the organic solvent to form vesicles, and then placing the vesicles in an alkaline aqueous solution for self-assembly to form a hydrogel.

[0008] Preferably, the alkaline aqueous solution includes NaOH solution, KOH solution and PBS buffer solution.

[0009] Preferably, the organic solvent includes methanol and ethanol.

[0010] More preferably, the method of directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution for self-assembly to form a hydrogel comprises the following steps: weighing sodium aescinate and hydroxysafflor yellow A and dissolving them in an alkaline aqueous solution to obtain an aqueous solution; then heating the obtained aqueous solution at a constant temperature, and cooling it at room temperature to obtain a sodium aescinate-hydroxysafflor yellow A hydrogel.

[0011] More preferably, the method of first dissolving sodium aescinate and hydroxysafflor yellow A in an organic solvent and then removing the organic solvent to form vesicles and then placing the vesicles in an alkaline aqueous solution for self-assembly to form a hydrogel comprises the following steps: weighing sodium aescinate and hydroxysafflor yellow A and dissolving them in an organic solvent to obtain an organic solution; removing the organic solvent from the obtained organic solution to obtain vesicles; then dissolving the obtained vesicles in an alkaline aqueous solution, heating at a constant temperature, and standing and cooling at room temperature to obtain sodium aescinate-hydroxysafflor yellow A hydrogel.

[0012] More preferably, the ratio of sodium aescinate to hydroxysafflor yellow A in an alkaline aqueous solution or an organic solvent is (0.5-100): (0.5-50) g / L. In a specific embodiment, the ratio of sodium aescinate to hydroxysafflor yellow A in an alkaline aqueous solution or an organic solvent is (8-60): (1-30) g / L.

[0013] More preferably, the pH of the alkaline aqueous solution is 8.0 to 14.0.

[0014] More preferably, the temperature of the constant temperature heating is 30-100°C.

[0015] The sodium aescinate-hydroxysafflor yellow A hydrogel prepared by the above preparation method.

[0016] Application of the sodium aescinate-hydroxysafflor yellow A hydrogel in the preparation of a drug for treating sepsis.

[0017] Beneficial effects: 1. The present invention provides a method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel. The preparation method is simple and stable, and can prepare an injectable sodium aescinate-hydroxysafflor yellow A hydrogel with high stability. The sodium aescinate-hydroxysafflor yellow A hydrogel has a significant therapeutic effect on sepsis in mice; 2. The raw materials sodium aescinate and hydroxysafflor yellow A used in the sodium aescinate-hydroxysafflor yellow A hydrogel obtained by the present invention are both natural products, and no other auxiliary materials or complex reagents, catalysts, etc. need to be added. It has high safety, good biocompatibility, and is biodegradable, and is suitable for use in the pharmaceutical field; 3. The applicant previously prepared an injectable hydrogel of aescin (see patent CN111249226A). The principle is to dissolve aescin in an alkaline aqueous solution, and aescin self-assembles into nanofibers through non-covalent forces such as hydrogen bonds, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds. The nanofibers further self-assemble into a hydrogel with a three-dimensional network structure. Before proposing the technical solution of the present invention, the applicant tried several other natural products and sodium aescinate hydrogels, but none of them achieved the expected effect. This is mainly because these natural products will affect the non-covalent forces such as hydrogen bonds, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds between aescin molecules when they coexist with sodium aescinate, interfering with their self-assembly to form nanofibers and then hydrogels. The applicant unexpectedly discovered that hydroxysafflor yellow A and sodium aescinate can form a hydrogel that is injectable, highly stable, and achieves a sustained release effect. It can also simultaneously exert the pharmacological effects of the two natural products, hydroxysafflor yellow A and sodium aescinate. 4. The sodium aescinate-hydroxysafflor yellow A hydrogel of the present invention can be injected intravenously without blocking blood vessels. In the current prior art, injectable hydrogels are mainly administered locally in situ using polymers such as biopolysaccharides. There are relatively few hydrogels that can be injected intravenously without blocking blood vessels. Currently, there are reported supramolecular hydrogels composed of nanoparticles, liposomes, polypeptides, etc., among which there is almost no research on tail vein injection. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 These are digital photos of sodium aescinate-hydroxysafflor yellow A hydrogel, a is an alkaline aqueous solution, b is the hydrogel after 1 day, and c is the hydrogel after 30 days; Figure 2 These are the SEM and TEM images of sodium aescinate-hydroxysafflor yellow A hydrogel; Figure 3 The infrared spectrum and ultraviolet spectrum of sodium aescinate-hydroxysafflor yellow A hydrogel are shown; Figure 4 The injectability of sodium aescinate-hydroxysafflor yellow A hydrogel; Figure 5 The rheological behavior of sodium aescinate-hydroxysafflor yellow A hydrogel; a shows that the storage modulus (G') and loss modulus (G'') show typical gel behavior with the change of strain; b shows that the apparent viscosity decreases gradually with the increase of shear rate; Figure 6 is the XRD pattern of sodium aescinate-hydroxysafflor yellow A hydrogel; Figure 7 It is a hydrogel of sodium aescinate-hydroxysafflor yellow A (ES-HSYA@Gel), sodium aescinate (ES), and hydroxysafflor yellow A (HSYA). 1 H NMR spectrum; Figure 8 is the 7-day survival rate of mice in different groups (n=15); Fig. 9 is the body temperature of mice in different groups (n=15); Fig.10 is the body weight of mice in different groups (n=15). DETAILED DESCRIPTION

[0019] The essential contents of the present invention are described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited thereto.

[0020] Example 1: Preparation Example 8 mg of sodium aescinate and 1 mg of hydroxysafflor yellow A were weighed and dissolved in 1 mL of NaOH solution with a pH of 8 to obtain an aqueous solution. The obtained aqueous solution was then heated at a constant temperature of 30 °C for 48 h and allowed to stand and cool at room temperature to obtain sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-1).

[0021] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH value greater than 7, preferably a pH value of 8.0 to 14.0.

[0022] Example 2: Preparation Example Weigh 35 mg of sodium aescinate and 20 mg of hydroxysafflor yellow A and dissolve them in 15 mL of ethanol to obtain an ethanol solution. Use a rotary evaporator (water bath at 30-100°C) to remove the organic solvent from the obtained ethanol solution to obtain vesicle-1. Then, the obtained vesicle-1 was dissolved in 1 mL of NaOH solution with a pH of 12, heated at a constant temperature of 60°C for 12 hours, and cooled at room temperature to obtain sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2).

[0023] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH value greater than 7, preferably a pH value of 8.0 to 14.0.

[0024] Example 3: Preparation Example Weigh 60 mg of sodium aescinate and 30 mg of hydroxysafflor yellow A and dissolve them in 30 mL of methanol to obtain a methanol solution. The obtained methanol solution was kept at 70°C for 1 h, and the organic solvent was removed using a rotary evaporator (water bath 30~100°C) to obtain vesicle-2. The obtained vesicle-2 was then dissolved in 1 mL of NaOH solution with a pH of 14, heated at 100°C for 0.5 h, and cooled at room temperature to obtain sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-3).

[0025] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH value greater than 7, preferably a pH value of 8.0 to 14.0.

[0026] Example 4: Morphology characterization and performance testing 1. Appearance and morphology characterization The appearance of the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 was recorded with a digital camera. Figure 1 As shown in the figure (a is the alkaline aqueous solution before gelation, b is the hydrogel after 1 day, and c is the hydrogel after 30 days), there is no obvious change after 30 days of gelation, indicating that the hydrogel has good stability. The sodium aescinate-hydroxysafflor yellow A hydrogel prepared in other examples has similar properties.

[0027] 2. Micromorphology characterization Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the microscopic morphology of the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2. Figure 2 As shown in Figure a, SEM shows that the microscopic morphology of the hydrogel sample presents a three-dimensional network composed of hollow spherical shells and micron-sized fibers with a size of 0.1~1 μm, which may be related to the self-assembly of sodium aescinate-hydroxysafflor yellow A vesicles into fibers. TEM shows that the vesicle alkaline aqueous solution sample (i.e., the alkaline aqueous solution before gelation) is a spherical vesicle with a diameter of about 110 nm ( Figure 2 (b) It may be due to the self-assembly of the amphiphilic molecules sodium aescinate and hydroxysafflor yellow A in water. The vesicle structure is conducive to the cell uptake through endocytosis, which is of great significance for improving the bioavailability of drugs and prolonging the duration of drug action.

[0028] The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0029] 3. Infrared spectrum and ultraviolet spectrum Figure 3 The infrared spectrum and ultraviolet spectrum of the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2. In the infrared spectrum ( Figure 3 In a), sodium aescinate (ES), hydroxysafflor yellow A (HSYA), and ES-HSYA@Gel all showed OH stretching vibration peaks (3350 cm -1 ), the CH stretching vibration peaks of methyl and methylene (2920 cm -1 、2850 cm -1 and its bending vibration peak (1420 cm -1 、1380 cm -1 ), olefin = CH out-of-plane bending vibration peak (890 cm -1 In addition, the CO stretching vibration peaks of the ether bond and hydroxyl group in sodium aescinate (1240 cm -1 , 1170 cm -1 The vibration peak of the benzene ring skeleton in hydroxysafflor yellow A (1560 cm -1 Left and right) are retained in ES-HSYA@Gel. In the UV-Vis spectrum ( Figure 3 In (b), the characteristic absorption peaks of sodium aescinate are located at 200 nm and 220 nm, which are related to the n→π* transition of C=C and C=O in its molecular structure. The characteristic absorption peaks of hydroxysafflor yellow A are located at 195 nm, 223 nm, 260 nm, 330 nm, and 400 nm. This is because the molecular structure contains benzene rings, C=C, C=O and is conjugated, and the absorption in the ultraviolet and visible light regions is strong. The ultraviolet absorption peak position of ES-HSYA@Gel at 207 nm is red-shifted, the ultraviolet absorption peak intensities at 260 nm and 330 nm are relatively increased, and the ultraviolet absorption peak intensity at 400 nm is relatively reduced, which may be due to the molecular structure changes of sodium aescinate and hydroxysafflor yellow A during the gelation process.

[0030] The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0031] 4. Injectability Figure 4It shows that the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 has a smooth injection process without obvious blockage, quickly recovers to a stable gel at room temperature, and maintains a good shape, has the potential for local administration, and provides a good platform for drug delivery and tissue engineering. The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0032] 5. Rheological behavior The strain scan was performed on the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2. Figure 5 As shown in a, the storage modulus (G') and loss modulus (G'') show typical gel behavior with the change of strain. In the low strain range, they are constant, and G' is higher than G'', showing a solid behavior dominated by elasticity and a stable network structure. When the strain exceeds 10%, G' decreases and G'' increases, and the hydrogel changes from elastic behavior to viscous behavior until the intersection hydrogel structure is destroyed and flows. The viscosity of the hydrogel is scanned, as shown in Figure 5 As shown in b, at low shear rate, the hydrogel exhibits a high viscosity. As the shear rate increases, the apparent viscosity gradually decreases, the gel dissociates, and the fluidity increases. The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0033] 6. XRD spectrum X-ray diffraction analysis was performed on the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2. Figure 6 Sodium aescinate (8°, 12°, 40°), hydroxysafflor yellow A (8°, 23°), and hydrogel (8°, 12°, 23°) showed diffraction peaks. The diffraction peaks of the hydrogels corresponded to the diffraction peaks of the single components, but the peak intensity was significantly reduced, which may be due to the formation of a large number of amorphous regions in the hydrogels, resulting in reduced crystallinity. The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other embodiments have similar properties.

[0034] 7. 1 H NMR spectrum Figure 7 The sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 1 H NMR spectrum of sodium aescinate 1The H NMR spectrum shows multiple characteristic peaks, corresponding to the complex proton environment in the steroidal saponin structure. In the higher field region (δ 0.5 ~ 2.0 ppm), the peaks are -CH 3 、-CH 2 -H; while in the lower field region (δ 3.0 ~ 5.0 ppm), -O-CH 2 -, -O-CH-, -CH=CH-, and H in the chemical shift caused by the adjacent group (such as C=O). The sodium aescinate-hydroxysafflor yellow A hydrogel prepared in other examples has similar properties.

[0035] Example 5: Animal Experiment 1. Experimental Animals 75 6-8 week old C57BL / 6 male mice, weighing 22±1 g, were obtained from Henan Sikebes Experimental Animal Co., Ltd., animal certificate number: SCXK (Yu) 2020-0005. They were raised in the animal room of Changsha Medical College, with the ambient temperature controlled at 20±1℃, relative humidity at 50±10%, and a photoperiod of 12 h light / 12 h dark. Standard feed and sterilized drinking water were provided, and food and water were available ad libitum.

[0036] 2. Experimental reagents Dexamethasone sodium phosphate injection (Hubei Jinyao Pharmaceutical Co., Ltd., national medicine standard H42020019), hydroxysafflor yellow A (Nanjing Chunqiu Bioengineering Co., Ltd., purity 98%), sodium aescinate (Shanghai Yuanye Biotechnology Co., Ltd., purity 98%), ES-HSYA@Gel hydrogel is ES-HSYA@Gel-2 prepared in Example 2, and the preparation method of ES@Gel hydrogel is the same as that of ES-HSYA@Gel hydrogel, except that HSYA is not added. Gas anesthesia machine. All reagents were prepared and used according to the instructions or experimental requirements, and the storage conditions met the reagent requirements.

[0037] 3. Experimental methods After one week of adaptive feeding, the mice were randomly divided into 5 groups, including the model group (CLP group), hydroxysafflor yellow A aqueous solution group (HSYA group), sodium aescinate hydrogel group (ES@Gel group), sodium aescinate-hydroxysafflor yellow A hydrogel group (ES-HSYA@Gel group), and dexamethasone group (DEX group), 15 in each group. Modeling method: The sepsis model was established by anesthetizing mice, exposing the midline incision of the abdomen, ligating the cecum (about 60% of the length), puncturing the cecum with a sterile 21G needle, squeezing out a small amount of feces, and then returning the cecum and closing the abdomen. After surgery, 1 ml of normal saline was injected subcutaneously to promote recovery. 4 hours after modeling, each group was given a dose of drug by tail vein injection once, and no drug was given again. The survival rate of mice was observed for 7 consecutive days, and the body temperature and weight of mice were recorded. Graphpad Prism 9.5.0 statistical software was used for statistical analysis, and P < 0.05 was considered statistically significant.

[0038] CLP group: Model mice were injected with an equal volume of PBS solution via the tail vein, once 4 hours after modeling, and observed for 7 consecutive days.

[0039] HSYA group: Model mice were injected with hydroxysafflor yellow A aqueous solution in the tail vein. The dosage was 4.5 mg / kg based on the weight of the mice. The mice were injected once in the tail vein 4 hours after modeling and observed for 7 consecutive days. ES@Gel group: model mice were injected with sodium aescinate hydrogel (ES@Gel) via tail vein. The dosage was based on the body weight of the mice, calculated as sodium aescinate, and the dose was 6.8 mg / kg. The mice were injected into the tail vein once 4 hours after modeling, and the mice were observed for 7 consecutive days. ES-HSYA@Gel group: ES-HSYA@Gel was injected into the tail vein of model mice. The dosage was 11.3 mg / kg according to the body weight of mice, including 6.8 mg / kg sodium aescinate and 4.5 mg / kg hydroxysafflor yellow A. The mice were injected into the tail vein once 4 hours after modeling and observed for 7 consecutive days. Dexamethasone group: Model mice were injected with dexamethasone aqueous solution through the tail vein. The dosage was 2 mg / kg according to the body weight of the mice. The drug was injected into the tail vein once 4 hours after modeling and the mice were observed for 7 consecutive days.

[0040] ①Body temperature analysis: Record the changes in body temperature of each group of mice in the morning and evening 7 days after administration.

[0041] ② Body weight analysis: Record the body weight changes of each group of mice in the morning and evening 7 days after administration.

[0042] 4. Experimental results Figure 8The 7-day survival rate of mice in different groups (n=15) is shown. Compared with the CLP group, the hydroxysafflor yellow A aqueous solution (HYSA) group and the dexamethasone (DEX) group did not significantly improve the 7-day survival rate of mice (P>0.05), while the sodium aescinate hydrogel (ES@Gel) group and the aescinate-hydroxysafflor yellow A hydrogel (HSYA-ES@Gel) group could improve the 7-day survival rate of mice (P<0.05), with the HSYA-ES@Gel group having the best effect (P<0.0001), indicating that the hydrogel has a significant therapeutic effect on sepsis in mice.

[0043] Fig. 9 The body temperature of mice in different groups (n=15) is shown. Except for the HSYA-ES@Gel group, which had a relatively constant body temperature, the other groups showed remittent fever (the difference between morning and evening body temperature was >2°C), indicating that the HSYA-ES@Gel group can maintain the body temperature of septic mice.

[0044] Fig.10 The weights of mice in different groups (n=15) are shown. The weight changes of mice in each group were almost the same, and the mice were in good condition.

[0045] In summary: 1. The present invention provides a method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel. The preparation method is simple and stable, and can prepare an injectable sodium aescinate-hydroxysafflor yellow A hydrogel with high stability. The sodium aescinate-hydroxysafflor yellow A hydrogel has a significant therapeutic effect on sepsis in mice; 2. The raw materials sodium aescinate and hydroxysafflor yellow A used in the sodium aescinate-hydroxysafflor yellow A hydrogel obtained by the present invention are both natural products, and no other auxiliary materials or complex reagents, catalysts, etc. need to be added. It has high safety, good biocompatibility, and is biodegradable, and is suitable for use in the pharmaceutical field; 3. The applicant previously prepared an injectable hydrogel of aescin (see patent CN111249226A). The principle is to dissolve aescin in an alkaline aqueous solution, and aescin self-assembles into nanofibers through non-covalent forces such as hydrogen bonds, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds. The nanofibers further self-assemble into a hydrogel with a three-dimensional network structure. Before proposing the technical solution of the present invention, the applicant tried several other natural products and sodium aescinate hydrogels, but none of them achieved the expected effect. This is mainly because these natural products will affect the non-covalent forces such as hydrogen bonds, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds between aescin molecules when they coexist with sodium aescinate, interfering with their self-assembly to form nanofibers and then hydrogels. The applicant unexpectedly discovered that hydroxysafflor yellow A and sodium aescinate can form a hydrogel that is injectable, highly stable, and achieves a sustained release effect. It can also simultaneously exert the pharmacological effects of the two natural products, hydroxysafflor yellow A and sodium aescinate. 4. The sodium aescinate-hydroxysafflor yellow A hydrogel of the present invention can be injected intravenously without blocking blood vessels. In the current prior art, injectable hydrogels are mainly administered locally in situ using polymers such as biopolysaccharides. There are relatively few hydrogels that can be injected intravenously without blocking blood vessels. Currently, there are reported supramolecular hydrogels composed of nanoparticles, liposomes, polypeptides, etc., among which there is almost no research on tail vein injection.

[0046] The purpose of the above-mentioned embodiments is to specifically introduce the essential content of the present invention, but those skilled in the art should know that the protection scope of the present invention should not be limited to the specific embodiments.

Claims

1. A method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel, characterized in that: The method comprises the following steps: directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution to self-assemble into a hydrogel; or firstly dissolving sodium aescinate and hydroxysafflor yellow A in an organic solvent and then removing the organic solvent to form vesicles, and then placing the vesicles in an alkaline aqueous solution to self-assemble into a hydrogel.

2. The preparation method according to claim 1, characterized in that: The alkaline aqueous solution is one or more of a NaOH solution, a KOH solution and a PBS buffer solution.

3. The preparation method according to claim 1, characterized in that: The organic solvent is one or more of methanol and ethanol.

4. The preparation method according to claim 1, characterized in that: The method for directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution for self-assembly to form a hydrogel comprises the following steps: weighing sodium aescinate and hydroxysafflor yellow A and dissolving them in an alkaline aqueous solution to obtain an aqueous solution; then heating the obtained aqueous solution at a constant temperature, standing and cooling at room temperature to obtain a sodium aescinate-hydroxysafflor yellow A hydrogel; firstly dissolving sodium aescinate and hydroxysafflor yellow A in an organic solvent, then removing the organic solvent to form vesicles, and then placing the vesicles in an alkaline aqueous solution for self-assembly to form a hydrogel comprises the following steps: weighing sodium aescinate and hydroxysafflor yellow A and dissolving them in an organic solvent to obtain an organic solution; removing the organic solvent from the obtained organic solution to obtain vesicles; then dissolving the obtained vesicles in an alkaline aqueous solution, heating at a constant temperature, standing and cooling at room temperature to obtain a sodium aescinate-hydroxysafflor yellow A hydrogel.

5. The preparation method according to claim 4, characterized in that: The ratio of sodium aescinate and hydroxysafflor yellow A in the alkaline aqueous solution or organic solvent is (0.5-100): (0.5-50) g / L.

6. The preparation method according to claim 4, characterized in that: The pH of alkaline aqueous solution is 8.0~14.

0.

7. The preparation method according to claim 4, characterized in that: The temperature of constant temperature heating is 30~100℃.

8. Aescinate-hydroxysafflor yellow A hydrogel prepared by the preparation method according to any one of claims 1 to 7.

9. Use of the sodium aescinate-hydroxysafflor yellow A hydrogel according to claim 8 in the preparation of a medicament for treating sepsis.

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