Aescin-saffloryellow A hydrogel, preparation method thereof and application thereof in sepsis

Abstract

The present invention discloses a sodium aescinate-hydroxysafflor yellow A hydrogel, a preparation method, and its application in sepsis. The present invention provides a method for preparing the sodium aescinate-hydroxysafflor yellow A hydrogel. The preparation method is simple and stable, and can produce an injectable, highly stable sodium aescinate-hydroxysafflor yellow A hydrogel. The sodium aescinate-hydroxysafflor yellow A hydrogel has a significant therapeutic effect on sepsis in mice. 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 excipients or complex reagents or catalysts are required. The hydrogel has high safety, good biocompatibility, and is biodegradable.

Description

Technical Field

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

[0002] Sepsis is a systemic inflammatory response syndrome triggered by infection. It results from an imbalance in the body's immune response to bacterial, viral, fungal, or parasitic infections, leading to endothelial damage, microcirculatory impairment, and tissue hypoxia, which in turn trigger multiple organ dysfunction and even failure. It is a leading cause of death in intensive care units (ICUs) worldwide. Sepsis typically progresses rapidly, and if not promptly addressed, it can deteriorate into severe sepsis or septic shock. The latter is accompanied by persistent hypotension and carries a very high mortality rate. Currently, the main treatment options include early use of antibiotics, supportive therapy, and fluid resuscitation.

[0003] Safflower, also known as crocus or saffron, is widely cultivated in my country for its dried tubular flowers, which are used as a traditional Chinese medicine for promoting blood circulation, removing blood stasis, and relieving pain. Safflower petals contain a variety of active ingredients, among which the representative quality marker, Hydroxysafflor Yellow A (HSYA), belongs to the flavonoid class. Its molecule contains multiple hydrogen bonds and unsaturated double bonds. It exhibits antioxidant properties by scavenging free radicals and inhibiting lipid peroxidation, while also inhibiting the release of inflammatory mediators and regulating related signaling pathways. HSYA has potential for use in drug delivery systems (such as hydrogels and nanoparticles) to treat cardiovascular and cerebrovascular diseases, arthritis, and other conditions.

[0004] Currently, there are no reports of hydroxysafflor yellow A being formulated into a hydrogel, let alone an injectable hydrogel. Currently, injectable hydrogels primarily utilize polymers such as biopolysaccharides for localized in situ administration. Hydrogels that can be injected intravenously without clogging blood vessels are relatively rare. Currently reported are supramolecular hydrogels composed of nanoparticles, liposomes, and peptides, but there is virtually no research on tail vein injection.

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

[0006] The first object of the present invention is to provide a method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel, the second object is to provide a sodium aescinate-hydroxysafflor yellow A hydrogel prepared by the preparation method, and the third object is to provide a use 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:

[0008] 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 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.

[0009] Preferably, the alkaline aqueous solution includes NaOH solution, KOH solution and PBS buffer solution.

[0010] Preferably, the organic solvent includes methanol and ethanol.

[0011] More preferably, the method of directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution to self-assemble into 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.

[0012] 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; and 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.

[0013] More preferably, the ratio of sodium aescinate to hydroxysafflor yellow A in the alkaline aqueous solution or 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 the alkaline aqueous solution or organic solvent is (8-60): (1-30) g / L.

[0014] More preferably, the pH of the alkaline aqueous solution is 8.0 to 14.0.

[0015] More preferably, the constant temperature heating temperature is 30-100°C.

[0016] The sodium aescinate-hydroxysafflor yellow A hydrogel prepared by the above preparation method.

[0017] Application of the sodium aescinate-hydroxysafflor yellow A hydrogel in the preparation of a drug for treating sepsis.

[0018] Beneficial effects:

[0019] 1. The present invention provides a method for preparing a sodium aescinate-hydroxysafflor yellow A hydrogel. The preparation method is simple and stable, and can produce an injectable, highly stable sodium aescinate-hydroxysafflor yellow A hydrogel. The sodium aescinate-hydroxysafflor yellow A hydrogel has a significant therapeutic effect on sepsis in mice.

[0020] 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;

[0021] 3. The applicant previously prepared an injectable aescin hydrogel (see patent CN111249226A). The principle is to dissolve aescin in an alkaline aqueous solution, and the aescin self-assembles into nanofibers through non-covalent forces such as hydrogen bonding, 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 to form hydrogels with several other natural products and sodium aescin, but none of them achieved the expected effect. This is mainly because when these natural products coexist with sodium aescin, they affect the non-covalent forces such as hydrogen bonding, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds between aescin molecules, interfering with their self-assembly into nanofibers and then forming a hydrogel. The applicant unexpectedly discovered that hydroxysafflor yellow A and sodium aescin can form a hydrogel that is injectable, highly stable, and achieves a sustained-release effect. It can also simultaneously exert the pharmacological effects of both hydroxysafflor yellow A and sodium aescin.

[0022] 4. The sodium aescinate-hydroxysafflor yellow A hydrogel of the present invention can be injected intravenously without clogging blood vessels. Currently, injectable hydrogels in the prior art primarily use polymers such as biopolysaccharides for in situ local administration. However, few hydrogels can be injected intravenously without clogging blood vessels. Currently reported supramolecular hydrogels composed of nanoparticles, liposomes, and polypeptides have been studied, but there is little research on hydrogels that can be injected intravenously. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] 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;

[0024] Figure 2 These are the SEM and TEM images of sodium aescinate-hydroxysafflor yellow A hydrogel;

[0025] Figure 3These are the infrared and ultraviolet spectra of sodium aescinate-hydroxysafflor yellow A hydrogel;

[0026] Figure 4 The injectability of sodium aescinate-hydroxysafflor yellow A hydrogel;

[0027] Figure 5 The rheological behavior of sodium aescinate-hydroxysafflor yellow A hydrogel; Figure a shows that the storage modulus (G') and loss modulus (G'') change with strain, showing typical gel behavior; Figure b shows that the apparent viscosity gradually decreases with increasing shear rate;

[0028] Figure 6 This is the XRD pattern of sodium aescinate-hydroxysafflor yellow A hydrogel;

[0029] Figure 7 Sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel), sodium aescinate (ES), hydroxysafflor yellow A (HSYA) 1 H NMR spectrum;

[0030] Figure 8 is the 7-day survival rate of mice in different groups (n=15);

[0031] Figure 9 is the body temperature of mice in different groups (n=15);

[0032] Figure 10 Figure 5. Body weights of mice in different groups (n=15). DETAILED DESCRIPTION

[0033] The essential contents of the present invention are described in detail below with reference to the embodiments, but the protection scope of the present invention is not limited thereto.

[0034] Example 1: Preparation Example

[0035] 8 mg of sodium aescinate and 1 mg of hydroxysafflor yellow A were weighed and dissolved in 1 mL of NaOH solution (pH 8) to obtain an aqueous solution. The resulting aqueous solution was then heated at 30°C for 48 h and allowed to cool at room temperature to obtain the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-1).

[0036] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH greater than 7, preferably a pH of 8.0 to 14.0.

[0037] Example 2: Preparation Example

[0038] 35 mg of sodium aescinate and 20 mg of hydroxysafflor yellow A were weighed and dissolved in 15 mL of ethanol to obtain an ethanol solution. The organic solvent was removed from the ethanol solution using a rotary evaporator (water bath temperature ranged from 30°C to 100°C) to obtain vesicle-1. Vesicle-1 was then dissolved in 1 mL of NaOH solution (pH 12), heated at 60°C for 12 hours, and allowed to cool at room temperature to obtain the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2).

[0039] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH greater than 7, preferably a pH of 8.0 to 14.0.

[0040] Example 3: Preparation Example

[0041] 60 mg of sodium aescinate and 30 mg of hydroxysafflor yellow A were weighed and dissolved in 30 mL of methanol to obtain a methanol solution. The resulting methanol solution was incubated at 70°C for 1 hour. The organic solvent was removed using a rotary evaporator (water bath at 30-100°C) to obtain vesicle-2. Vesicle-2 was then dissolved in 1 mL of NaOH solution (pH 14), heated at 100°C for 0.5 hour, and allowed to cool at room temperature to obtain sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-3).

[0042] The NaOH solution may also be replaced by other alkaline aqueous solutions, such as KOH solution, PBS buffer solution, with a pH greater than 7, preferably a pH of 8.0 to 14.0.

[0043] Example 4: Morphology characterization and performance testing

[0044] 1. Appearance and morphology characterization

[0045] The appearance of the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 was recorded using a digital camera. Figure 1 As shown (a: alkaline aqueous solution before gelation, b: hydrogel after 1 day, c: hydrogel after 30 days), there was no significant change 30 days after gelation, indicating that the hydrogel has good stability. Sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0046] 2. Micromorphology characterization

[0047] 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 (a), SEM shows that the hydrogel sample microstructure presents a three-dimensional network consisting of hollow spherical shells with a size of 0.1-1 μm and micron-sized fibers, 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) This 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 cell uptake through endocytosis, which is of great significance for improving the bioavailability of drugs and prolonging the duration of drug action.

[0048] The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0049] 3. Infrared spectrum and ultraviolet spectrum

[0050] Figure 3 The infrared spectrum and ultraviolet spectrum of the sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2. 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 Around) 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 Around) are retained in ES-HSYA@Gel. In the UV-Vis spectrum ( Figure 3In Figure (b), sodium aescinate exhibits characteristic absorption peaks at 200 nm and 220 nm, associated with n→π* transitions between C=C and C=O in its molecular structure. Hydroxysafflor yellow A exhibits characteristic absorption peaks at 195 nm, 223 nm, 260 nm, 330 nm, and 400 nm. This is due to the presence of benzene rings, C=C, and C=O in its molecular structure, as well as its conjugated nature, resulting in strong absorption in the UV and visible regions. The ES-HSYA@Gel exhibits a red shift in the UV absorption peak at 207 nm, a relative increase in the UV absorption peaks at 260 nm and 330 nm, and a relative decrease in the UV absorption peak at 400 nm. This is likely due to changes in the molecular structures of sodium aescinate and hydroxysafflor yellow A during the gelation process.

[0051] The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples have similar properties.

[0052] 4. Injectability

[0053] Figure 4 The sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 demonstrated smooth injection without significant clogging. It quickly recovered into a stable gel at room temperature and maintained its shape, demonstrating its potential for localized administration and providing a promising platform for drug delivery and tissue engineering. The sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples exhibited similar properties.

[0054] 5. Rheological behavior

[0055] 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 Figure a, the storage modulus (G') and loss modulus (G'') exhibit typical gel behavior as a function of strain. Within the low strain range, they are constant, with G' higher than G'', indicating solid behavior dominated by elasticity and a stable network structure. When the strain exceeds 10%, G' decreases while G'' increases, and the hydrogel transitions from elastic to viscous behavior until the hydrogel structure at the intersection is destroyed and flow occurs. A viscosity sweep of the hydrogel is performed, as shown in Figure 3. Figure 5 As shown in Figure b, at low shear rates, 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.

[0056] 6. XRD pattern

[0057] 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°) exhibit diffraction peaks. These peaks correspond to those of the individual components, but the peak intensities are significantly lower, likely due to the formation of a large number of amorphous regions in the hydrogel, resulting in reduced crystallinity. Sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples exhibit similar properties.

[0058] 7. 1 H NMR spectrum

[0059] Figure 7 The sodium aescinate-hydroxysafflor yellow A hydrogel (ES-HSYA@Gel-2) prepared in Example 2 1 H NMR spectrum of sodium aescinate 1 The H NMR spectrum displays multiple characteristic peaks corresponding to the complex proton environment within the steroidal saponin structure. In the higher-field region (δ 0.5 to 2.0 ppm), these peaks are attributed to H atoms in -CH3 and -CH2- on the aliphatic ring and chain; in the lower-field region (δ 3.0 to 5.0 ppm), these peaks are attributed to H atoms in -O-CH2-, -O-CH-, and -CH=CH-, as well as H atoms chemically shifted by adjacent groups (such as C=O). Sodium aescinate-hydroxysafflor yellow A hydrogels prepared in other examples exhibit similar properties.

[0060] Example 5: Animal Experiment

[0061] 1. Experimental Animals

[0062] Seventy-five male C57BL / 6 mice, 6-8 weeks old, weighing 22 ± 1 g, were obtained from Henan Sikebes Laboratory Animal Co., Ltd. (animal qualification certificate number: SCXK (Yu) 2020-0005). They were maintained in the Changsha Medical College animal room at a controlled temperature of 20 ± 1°C, relative humidity of 50 ± 10%, and a 12-h light / 12-h dark photoperiod. Standardized chow and sterilized drinking water were available ad libitum.

[0063] 2. Experimental reagents

[0064] Dexamethasone sodium phosphate injection (Hubei Jinyao Pharmaceutical Co., Ltd., National Medicine Approval No. H42020019), Hydroxysafflor Yellow A (Nanjing Chunqiu Bioengineering Co., Ltd., purity 98%), Sodium Aescinate (Shanghai Yuanye Biotechnology Co., Ltd., purity 98%), ES-HSYA@Gel hydrogel was ES-HSYA@Gel-2 prepared in Example 2. The preparation method of ES@Gel hydrogel was the same as that of ES-HSYA@Gel hydrogel, except that HSYA was not added. Anesthesia machine. All reagents were prepared and used according to the instructions or experimental requirements, and the storage conditions met the reagent requirements.

[0065] 3. Experimental methods

[0066] After one week of adaptive feeding, mice were randomly divided into five groups: a model group (CLP), a hydroxysafflor yellow A aqueous solution group (HSYA group), a escinate hydrogel group (ES@Gel group), a escinate-hydroxysafflor yellow A hydrogel group (ES-HSYA@Gel group), and a dexamethasone group (DEX group), 15 in each group. Modeling methods: The sepsis model was established by anesthetizing mice, exposing the abdomen through a midline incision, ligating the cecum (approximately 60% of its length), puncturing the cecum with a sterile 21G needle, squeezing out a small amount of feces, then reinserting the cecum, and closing the abdomen. Postoperatively, 1 ml of normal saline was injected subcutaneously to promote recovery. Four hours after modeling, each group received a single tail vein injection of the drug according to the dose, followed by no further drug administration. Survival rates of the mice were observed for 7 consecutive days, and body temperatures and body weights were recorded. Statistical analysis was performed using GraphPad Prism 9.5.0 software. P < 0.05 was considered statistically significant.

[0067] CLP group: Model mice were injected with an equal volume of PBS solution via the tail vein 4 hours after modeling and then observed for 7 consecutive days.

[0068] HSYA group: Model mice were injected with hydroxysafflor yellow yellow A aqueous solution in the tail vein. The dosage was based on the body weight of the mice, calculated as hydroxysafflor yellow A, and the dose was 4.5 mg / kg. The mice were injected into the tail vein once 4 hours after modeling and observed for 7 consecutive days.

[0069] ES@Gel group: Model mice were injected with sodium aescinate hydrogel (ES@Gel) via tail vein. The dose was based on the body weight of the mice, calculated as sodium aescinate, at a dose of 6.8 mg / kg. The mice were injected once into the tail vein 4 hours after modeling and observed for 7 consecutive days.

[0070] ES-HSYA@Gel group: Model mice were injected with ES-HSYA@Gel via the tail vein. The dose was 11.3 mg / kg based on the body weight of the mice, including 6.8 mg / kg sodium aescinate and 4.5 mg / kg hydroxysafflor yellow A. The mice were injected once into the tail vein 4 hours after modeling and observed for 7 consecutive days.

[0071] Dexamethasone group: Model mice were injected with dexamethasone aqueous solution through the tail vein. The dose was 2 mg / kg according to the body weight of the mice. The dexamethasone was injected into the tail vein once 4 hours after modeling and the mice were observed for 7 consecutive days.

[0072] ①Body temperature analysis: Record the changes in body temperature of mice in each group in the morning and evening for 7 days after administration.

[0073] ② Body weight analysis: Record the body weight changes of mice in each group in the morning and evening 7 days after administration.

[0074] 4. Experimental results

[0075] Figure 8 The 7-day survival rates of mice in different groups (n=15) are shown. Compared with the CLP group, the hydroxysafflor yellow A aqueous solution (HYSA) and dexamethasone (DEX) groups did not significantly improve the 7-day survival rates of mice (P>0.05). However, the sodium aescinate hydrogel (ES@Gel) and aescinate-hydroxysafflor yellow A hydrogel (HSYA-ES@Gel) groups improved the 7-day survival rates of mice (P<0.05), with the HSYA-ES@Gel group showing the best effect (P<0.0001), indicating that the hydrogel has a significant therapeutic effect on sepsis in mice.

[0076] Figure 9 The body temperatures of mice in different groups (n=15) are shown. Except for the HSYA-ES@Gel group, which maintained a relatively constant body temperature, the other groups exhibited remittent fever (a temperature difference between morning and evening greater than 2°C), indicating that the HSYA-ES@Gel group can maintain the body temperature of septic mice.

[0077] Figure 10 The weights of mice in different groups (n=15) are shown. The weight changes of mice in each group were almost identical, and the mice were in good condition.

[0078] In summary:

[0079] 1. The present invention provides a method for preparing a sodium aescinate-hydroxysafflor yellow A hydrogel. The preparation method is simple and stable, and can produce an injectable, highly stable sodium aescinate-hydroxysafflor yellow A hydrogel. The sodium aescinate-hydroxysafflor yellow A hydrogel has a significant therapeutic effect on sepsis in mice.

[0080] 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;

[0081] 3. The applicant previously prepared an injectable aescin hydrogel (see patent CN111249226A). The principle is to dissolve aescin in an alkaline aqueous solution, and the aescin self-assembles into nanofibers through non-covalent forces such as hydrogen bonding, 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 to form hydrogels with several other natural products and sodium aescin, but none of them achieved the expected effect. This is mainly because when these natural products coexist with sodium aescin, they affect the non-covalent forces such as hydrogen bonding, π-π stacking, electrostatic forces, van der Waals forces, and coordination bonds between aescin molecules, interfering with their self-assembly into nanofibers and then forming a hydrogel. The applicant unexpectedly discovered that hydroxysafflor yellow A and sodium aescin can form a hydrogel that is injectable, highly stable, and achieves a sustained-release effect. It can also simultaneously exert the pharmacological effects of both hydroxysafflor yellow A and sodium aescin.

[0082] 4. The sodium aescinate-hydroxysafflor yellow A hydrogel of the present invention can be injected intravenously without clogging blood vessels. Currently, injectable hydrogels in the prior art primarily use polymers such as biopolysaccharides for in situ local administration. However, few hydrogels can be injected intravenously without clogging blood vessels. Currently reported supramolecular hydrogels composed of nanoparticles, liposomes, and polypeptides have been studied, but there is little research on hydrogels that can be injected intravenously.

[0083] The purpose of the above 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 this specific embodiment.

Claims

1. A method for preparing sodium aescinate-hydroxysafflor yellow A hydrogel, characterized in that: The steps include: A method for self-assembling a hydrogel by directly placing sodium aescinate and hydroxysafflor yellow A in an alkaline aqueous solution 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 allowing it to cool at room temperature to obtain a sodium aescinate-hydroxysafflor yellow A hydrogel; Alternatively, sodium aescinate and hydroxysafflor yellow A are first dissolved in an organic solvent, the organic solvent is subsequently removed to form vesicles, and the vesicles are then placed in an alkaline aqueous solution for self-assembly to form a hydrogel, comprising the following steps: sodium aescinate and hydroxysafflor yellow A are weighed and dissolved in an organic solvent to obtain an organic solution; the organic solvent is removed from the obtained organic solution to obtain vesicles; and the obtained vesicles are then dissolved in an alkaline aqueous solution, heated at a constant temperature, and allowed to cool at room temperature to obtain a sodium aescinate-hydroxysafflor yellow A hydrogel.

2. The preparation method according to claim 1, wherein: 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, wherein: The organic solvent is one or more of methanol and ethanol.

4. The preparation method according to claim 1, wherein: 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.

5. The preparation method according to claim 1, wherein: The pH of alkaline aqueous solution is 8.0~14.

0.

6. The preparation method according to claim 1, wherein: The constant temperature heating temperature is 30~100℃.

7. Aescinate-hydroxysafflor yellow A hydrogel prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the sodium aescinate-hydroxysafflor yellow A hydrogel according to claim 7 in the preparation of a medicament for treating sepsis.

Images