Self-assembling hydrogels and methods of making and using the same

Abstract

The application belongs to the field of medicine, and discloses a self-assembled hydrogel, which is a hydrogel prepared from a phosphate buffer and ginger-like notoginseng saponin R1. The self-assembled hydrogel has good stability, viscoelasticity, biocompatibility and antibacterial capacity, can stably act on a tissue affected part in a self-healing manner alone or in a form of carrying other drugs, and improves the diagnosis and treatment effect, especially the diagnosis and treatment effect of diseases based on antibacterial and anti-inflammatory requirements. Meanwhile, the application also provides a preparation method and application of the self-assembled hydrogel, and especially a use as a gel medicine for treating vaginitis.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a self-assembled hydrogel and its preparation method and use. BACKGROUND

[0002] Panax zingiberensis C.Y. Wu et K.M. Feng is a perennial herbaceous plant of the Araliaceae Panax genus. The root and rhizome of Panax zingiberensis C.Y. Wu et K.M. Feng is a traditional Chinese medicinal material with important medicinal value. The root and leaf of Panax zingiberensis C.Y. Wu et K.M. Feng can be used as medicine, as summarized in Chinese Herbal Medicine. Zingibroside R1 is a natural triterpenoid saponin, which is one of the main active ingredients of Panax zingiberensis C.Y. Wu et K.M. Feng and Panax notoginseng. It shows anti-tumor effect and anti-angiogenic activity, and has high value in medical and commercial fields. However, the biomedical activity of Zingibroside R1 has not been fully developed, and previous studies have mostly focused on content determination and chemical structure analysis. In addition, Zingibroside R1 has poor solubility and low bioavailability, and a delivery carrier or adjuvant is needed to improve its bioavailability during use. The introduction of a delivery carrier or adjuvant may cause unpredictable side effects, limiting its clinical application.

[0003] The patent literature related to the application of Zingibroside R1 or Panax notoginseng saponin R1 is as follows:

[0004] Patent application CN118340721A, entitled "Panax notoginseng saponin ophthalmic gel preparation, its preparation method and use", discloses the use of a thickening agent to form a gel system to deliver Panax notoginseng saponin, which includes Panax notoginseng saponin R1.

[0005] Patent application CN117258051A, entitled "Medical hydrogel composition, medical hydrogel and its preparation method and application", discloses the use of a carrier to deliver Panax notoginseng saponin R1.

[0006] Due to the solubility stability and bioavailability of Zingibroside R1, previous studies have used a large amount of cross-linking agent or preservative to deliver Panax notoginseng saponin R1. Therefore, the skilled person in the art has made various improvements on how to carry and release Panax notoginseng saponin.

[0007] Therefore, the present application attempts to further study Zingibroside R1 from the opposite direction to solve some inherent problems. SUMMARY

[0008] The present application aims to provide a self-assembled hydrogel, and the present application finds, through in-depth research on notoginsenoside R1, that the notoginsenoside R1 can make the gel have good stability, viscoelasticity, biocompatibility and antibacterial ability after the gelation in an aqueous solution, which means that the gel can stably act on a tissue affected part in a self-healing manner alone or in a form of carrying other drugs, and improve the diagnosis and treatment effect, especially the diagnosis and treatment effect of diseases based on the antibacterial and anti-inflammatory requirements.

[0009] Meanwhile, the present application also provides a preparation method and application of the self-assembled hydrogel.

[0010] To achieve the above-mentioned purpose, the present application discloses the following:

[0011] A self-assembled hydrogel, which is a hydrogel prepared from a phosphate buffer and notoginsenoside R1.

[0012] In the self-assembled hydrogel, the concentration of notoginsenoside R1 in the self-assembled hydrogel is 1.5-2.5 wt%.

[0013] In the self-assembled hydrogel, the self-assembled hydrogel does not contain any cross-linking agent, preservative or other organic compound; the solvent is a phosphate buffer (PBS); the pH of the phosphate buffer is 7-8, preferably, the pH of the phosphate buffer is 7.4, and the concentration of the phosphate buffer is 0.01M, i.e. 1× PBS.

[0014] Meanwhile, the present application also discloses a preparation method of the self-assembled hydrogel as described above, and the method is as follows:

[0015] Disperse notoginsenoside R1 in 1× PBS, mix with water under heating condition, and then cool to obtain a self-assembled hydrogel.

[0016] In the preparation method, the heating temperature is 90-100℃, and the heating time is 30-90min.

[0017] In addition, the present application also discloses the use of the self-assembled hydrogel as described above to prepare an antibacterial drug, or to prepare a drug carrier.

[0018] In the use, the active ingredients of the drug carrier carry one or more of probiotics, antibiotics and natural products.

[0019] In the use, the probiotics are one or more of lactobacillus rhamnosus, lactobacillus reuteri, bifidobacterium, lactobacillus acidophilus and escherichia coli Nissle 1917.

[0020] the antibiotic is one or more of doxorubicin, 5-fluorouracil, aureomycin;

[0021] the natural product is one or more of curcumin, berberine, rhein.

[0022] Finally, the present application also discloses a medicine comprising the self-assembled hydrogel as described above and a pharmaceutically active ingredient coated in the self-assembled hydrogel.

[0023] In the above medicine, the pharmaceutically active ingredient is one or more of probiotics, antibiotics, natural products; the probiotics are one or more of Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium, Lactobacillus acidophilus, Escherichia coli Nissle1917; the antibiotic is one or more of doxorubicin, 5-fluorouracil, aureomycin; the natural product is one or more of curcumin, berberine, rhein.

[0024] In the above medicine, the medicine is an oral medicine, a medicine applied on the skin, or a medicine directly placed in the vagina or the intestinal tract.

[0025] In the above medicine, the probiotics are Lactobacillus rhamnosus, and the medicine is a medicine for treating vaginitis.

[0026] In the above medicine, the self-assembled hydrogel carries 1x10 6 ~1x10 10 CFUs of Lactobacillus rhamnosus per milliliter.

[0027] The present application has at least the following beneficial effects:

[0028] 1. The ginger-like notoginseng saponin R1 self-assembled hydrogel of the present application has good stability, viscoelasticity, biocompatibility and antibacterial ability, which means that the gel can stably act on the affected tissue in a self-healing manner alone or in the form of carrying other drugs, thereby improving the diagnosis and treatment effect, especially the diagnosis and treatment effect of diseases based on the needs of antibacterial and anti-inflammatory;

[0029] 2. When the ginger-like notoginseng saponin R1 self-assembled hydrogel of the present application is used in the form of a drug carrier and combined with other pharmaceutically active ingredients, it has a drug loading rate of 100% and slow drug release characteristics.

[0030] In a more specific application scenario of the present application, the ginger-like notoginseng saponin R1 self-assembled hydrogel can effectively treat vaginitis by carrying probiotics and using vaginal local administration, without disturbing the vaginal microecology, having excellent viscoelasticity, effectively reducing the mechanical friction between tissues during implantation, and helping to reduce the discomfort that the patient may feel during administration. It can not only serve as a probiotic delivery carrier, but also exert its own efficacy in killing Candida albicans, forming a synergistic treatment that complements each other, not only relieving symptoms and reducing recurrence, but also reshaping a healthy vaginal microenvironment. BRIEF DESCRIPTION OF DRAWINGS

[0031] FIG. 1A A schematic diagram of the gelation process of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0032] FIG. 1B X-ray diffraction pattern of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0033] FIG. 1C Fourier transform infrared spectrum of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0034] FIG. 1D Zeta potential spectrum of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0035] FIG. 1E Gelation photos of the ginger-like notoginseng saponin R1 self-assembled hydrogel with different concentrations;

[0036] FIG. 2A Oscillatory mode-frequency sweep result graph of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0037] FIG. 2B Oscillatory mode-amplitude sweep result graph of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0038] FIG. 2C Continuous time strain sweep result graph of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0039] FIG. 3 Biocompatibility detection result graph of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0040] FIG. 4 Adhesion ability detection result photo of the ginger-like notoginseng saponin R1 self-assembled hydrogel;

[0041] FIG. 5A Photo of the inhibition ability of the ginger-like notoginseng saponin R1 self-assembled hydrogel on Candida albicans;

[0042] FIG. 5BFigure of the inhibitory ability of the self-assembled hydrogel of zingiberensis notoginseng saponin R1 on Candida albicans;

[0043] FIG. 6 Picture of the co-localization of the self-assembled hydrogel of zingiberensis notoginseng saponin R1 encapsulating probiotics.

[0044] FIG. 7A Picture of the progress of the treatment of mice with candidal vaginitis in each experimental group;

[0045] FIG. 7B Figure of the progress of the treatment of mice with candidal vaginitis in each experimental group;

[0046] FIG. 7C Picture of the pathological evaluation of the treatment of mice with candidal vaginitis in each experimental group;

[0047] FIG. 7D Picture of the fungal residues on the infected tissues of the treatment of mice with candidal vaginitis in each experimental group;

[0048] FIG. 8A Figure of the results of the composition of the vaginal microbiota of mice after the treatment of mice with candidal vaginitis in each experimental group;

[0049] FIG. 8B Figure of the PCoA principal coordinate analysis of the vaginal microecology of mice after the treatment of mice with candidal vaginitis in each experimental group. DETAILED DESCRIPTION

[0050] The present application will be described in detail below with reference to the embodiments thereof, and it should be noted that, in the description of the present application, no specific conditions are specified in the embodiments, and conventional conditions or manufacturer's recommended conditions are used. The reagents or instruments used are not specified by the manufacturer, and are all conventional products that can be purchased on the market.

[0051] First Part: Source and Description of Raw Materials

[0052] The "zingiberensis notoginseng saponin R1" mentioned in the embodiments has a white powder appearance, a molecular formula of C 42 H 66 O 14 .

[0053] The molecular structural formula of the zingiberensis notoginseng saponin R1 involved in the present application is:

[0054]

[0055] All animal experiments in the embodiments have been reviewed by the Hunan University Life Medical Ethics Review Committee, and if no special instructions are given, the probiotics used in the animal experiments are all Lactobacillus rhamnosus, and the concentration is 1×10 9CFU / mL, derived from BNCC187896.

[0056] Preparation and characterization of self-assembled hydrogel of notoginseng saponin R1

[0057] Example 1

[0058] Accurately weigh 3.00 mg of notoginseng saponin R1 powder into 200 μL of 1 × PBS, vortex ultrasonic mixing, then heated in a 100℃ oil bath for 60 min, and naturally cooled to obtain a 1.5% mass fraction of notoginseng saponin R1 self-assembled hydrogel.

[0059] Example 2

[0060] Accurately weigh 4.00 mg of notoginseng saponin R1 powder into 200 μL of 1 × PBS, vortex ultrasonic mixing, then heated in a 100℃ oil bath for 60 min, and naturally cooled to obtain a 2% mass fraction of notoginseng saponin R1 self-assembled hydrogel.

[0061] Example 3

[0062] Accurately weigh 5.00 mg of notoginseng saponin R1 powder into 200 μL of 1 × PBS, vortex ultrasonic mixing, then heated in a 100℃ oil bath for 60 min, and naturally cooled to obtain a 2.5% mass fraction of notoginseng saponin R1 self-assembled hydrogel.

[0063] The hydrogels of the above Examples 1 to 3 can all maintain stable hydrogel state under visual state, and the photos of the samples are referred to FIG. 1E .

[0064] Comparative Example 1

[0065] Accurately weigh 4.00 mg of notoginseng saponin R1 powder into 200 μL of physiological saline, vortex ultrasonic mixing, then heated in a 95℃ oil bath for 60 min, and naturally cooled to find that it cannot form a hydrogel.

[0066] As can be seen from the above Examples 1 to 3 and Comparative Example 2, the necessary condition for notoginseng saponin R1 to form a gel is to be dispersed in PBS solution.

[0067] The 2wt% hydrogel of the above Example 2 was further tested.

[0068] Third part Performance test of notoginseng saponin R1 self-assembled hydrogel

[0069] 3.1 Stability characterization of notoginseng saponin R1 self-assembled hydrogel

[0070] The gelation process of the hydrogels of Examples 1-3 is shown in FIG. 1A.

[0071] The gelation photos of the gels of different concentrations of the self-assembled hydrogels of notoginsenoside R1 of Examples 1-3 are shown in FIG. 1E.

[0072] The freeze-dried powder of the gel was then subjected to X-ray Diffraction (XRD) analysis and Fourier Transform infrared spectroscopy (FTIR) analysis, and the gel was subjected to Zeta potential analysis, and the results are shown in FIGS. 1F, 1G and 1H, respectively. FIG. 1B to FIG. 1D

[0073] Compared with the notoginsenoside R1 powder (ZR1), the diffraction peak of the self-assembled hydrogel of notoginsenoside R1 (ZR1 gel) is obvious, showing a crystal structure with ordered molecular arrangement; the FTIR spectrum shows enhanced O-H stretching vibration and carboxyl asymmetric and symmetric C=O stretching vibration red shift, indicating that hydrogen bonds are involved in the assembly process of the self-assembled hydrogel of notoginsenoside R1; in addition, the zeta potential of the self-assembled hydrogel of notoginsenoside R1 is -38.3 ± 0.47 mV, indicating that the stability of the self-assembled hydrogel of notoginsenoside R1 is improved compared with the solution.

[0074] 3.2 Viscoelasticity characterization of the self-assembled hydrogel of notoginsenoside R1

[0075] In this experiment, Anton Par MCR-92 system (Austria) rotary rheometer was used to perform dynamic and static viscoelasticity test on the self-assembled hydrogel of notoginsenoside R1.

[0076] The sample test temperature was 37°C, the test gap was 1 mm, and a thin layer of silicone oil was applied to the edge of the rotor and sample contact surface. The test parameter settings of different scanning modes are as follows: ① oscillation mode-frequency sweep: the angular frequency range was 0.1-100 rad / s, which changed logarithmically, and the strain value γ was constant at 0.2%; ② oscillation mode-amplitude sweep: the shear strain γ was set to change logarithmically from the starting value to the final value of 0.1%-100%, and the angular frequency value was constant at 6 rad / s; ③ continuous time strain sweep: first 25 data points were collected at 0.2% Strain, then 5 data points were collected at 500% Strain, and then 25 data points were collected at 0.2% Strain, the pressure change cycle was repeated three times, and the sample was repeatedly tested three times or more.

[0077] ​The test results are shown in Figure 2. In the oscillation mode-frequency scan, the storage modulus (G') of the self-assembled hydrogel of notoginsenoside R1 was always greater than the loss modulus (G") and did not show frequency dependence, proving that the sample was in a gel state and had good stability. In the oscillation mode-amplitude scan, when the shear strain γ reached 13%, the storage modulus (G') of the self-assembled hydrogel of notoginsenoside R1 was equal to the loss modulus (G"), indicating that it exhibited good equilibrium performance and stability under shear conditions. In the further continuous strain step scan, the self-assembled hydrogel of notoginsenoside R1 could still recover to its original state after multiple strain cycles of 0.2%-500%, proving that the sample has excellent self-healing ability.

[0078] 3.3 Biocompatibility of self-assembled hydrogel of ginger-like notoginsenoside R1

[0079] We incubated Caco-2 cell lines with self-assembled hydrogels containing 1.5%, 2%, and 2.5% (w / w) of notoginsenoside R1 for 6, 12, or 24 hours, respectively. Cell viability was then measured using the MTT assay, and the experiment was repeated three times. The results are shown below. FIG. 3 As shown, the self-assembled hydrogel of ginger-like notoginsenoside R1 has good biocompatibility and does not produce significant cytotoxicity to epithelial-like cells after incubation at 2% by mass for 24 hours.

[0080] 3.4 Determination of the tissue adhesion ability of the self-assembled hydrogel of notoginsenoside R1

[0081] 200 μL of ginger-like ginsenoside R1 self-assembled hydrogel was evenly applied to the bonding area of ​​a piece of fresh pigskin (approximately 10 cm²). 2 Then, another piece of pigskin was placed over the area where the hydrogel was applied and left to stand for a moment. One end of the pigskin pieces that were attached together was picked up with tweezers, and different weights were hung on the other end to test the adhesion of the ginger-like notoginsenoside R1 self-assembled hydrogel.

[0082] Experimental results are as follows FIG. 4 As shown, fresh pigskin that was bonded together after being coated with the self-assembled hydrogel of notoginseng saponin R1 could withstand a weight of 40 g, indicating that the self-assembled hydrogel of notoginseng saponin R1 has the ability to adhere to tissues.

[0083] 3.5 Determination of the antibacterial properties of the self-assembled hydrogel of notoginsenoside R1

[0084] Frozen Candida albicans (CA) was inoculated into SDS liquid medium and cultured at 37°C for 12 h in a shaking incubator to revive fungal activity. After centrifugation to remove the supernatant, the culture was adjusted to OD using fresh appropriate liquid medium. 630= 0.6, and 2% of the ginger Notoginseng saponins Rl self-assembled hydrogel was prepared. Experimental group: 200 μL of the culture medium containing OD 630 = 0.6 was added to the shaking tube, and then the ginger Notoginseng saponins Rl self-assembled hydrogel freeze-dried powder was added to the shaking tube to make the mass fraction 2%, and incubated for 2 h. Control group: 200 μL of the culture medium containing OD 630 = 0.6 was added to the shaking tube without treatment, and incubated for 2 h. After incubation, 10 7 μL was taken out and smeared on the SDS solid medium, and finally placed in a 37℃ incubator to wait for its growth. Finally, the growth of the colonies was counted. The experiment was repeated three times.

[0085] The antibacterial ability of the ginger Notoginseng saponins Rl gel on Candida albicans was evaluated by plate counting method. The results are shown in Figure 5. The ginger Notoginseng saponins Rl gel can significantly inhibit the activity of Candida albicans.

[0086] Part IV Preparation and performance characterization of ginger Notoginseng saponins Rl self-assembled hydrogel encapsulating probiotics

[0087] 4.1 Ginger Notoginseng saponins Rl self-assembled hydrogel for probiotic encapsulation and co-localization detection

[0088] The ginger Notoginseng saponins Rl self-assembled hydrogel of Example 2 was encapsulated with probiotics, and the preparation method was as follows:

[0089] 2% ginger Notoginseng saponins Rl solution was mixed with Congo red dye, and then heated in a 100℃ oil bath for 60 min, and naturally cooled to 37℃. 10 10 μL of the EcN-GFP probiotic with fluorescence was added, and the natural cooling was continued to form a gel. Laser confocal fluorescence microscope was used to observe the co-localization of the probiotics and the hydrogel.

[0090] The ginger Notoginseng saponins Rl self-assembled hydrogel was blended with probiotics, and after freeze-drying, scanning electron microscope was used to observe the co-localization of the probiotics and the hydrogel.

[0091] The experimental results are shown in FIG. 6 Figure 6. Laser confocal microscope and scanning electron microscope both observed that the probiotics were encapsulated in the ginger Notoginseng saponins Rl self-assembled hydrogel.

[0092] 4.2 Evaluation of the therapeutic effect of ginger Notoginseng saponins Rl self-assembled hydrogel probiotic delivery system on vaginitis mouse model

[0093] The 30 mice purchased were divided into 6 groups, namely ① blank group, ② control group, ③ probiotic group, ④ itraconazole group, ⑤ probiotic-ginsenoside R1 self-assembled hydrogel group, and ⑥ ginsenoside R1 self-assembled hydrogel group, five mice in each group. First, the mice model of candidal vaginitis was constructed: the mice in the experimental groups (groups ②-⑥) received intraperitoneal injection of 100 μL of benzoic acid estradiol (2 mg / mL) every day for six days, and then the experimental group mice were vaginally perfused with Candida albicans liquid (20 μL per mouse, OD 630 =0.6) for six days. After the modeling was completed, the mice were administered according to the group for nine days, during which 100 μL of the lavage fluid of each group of mice was collected and stored in a -80°C refrigerator, and when needed, the agar plate count was performed, and the body weight change and the appearance of the vagina of each group of mice were recorded. After the treatment was completed, the mice were sacrificed, the vaginal tissue was dissected, and pathological analysis was performed.

[0094] As shown in FIG. 7A, on the first day of infection with Candida albicans, the vaginas of all mice in the experimental groups appeared red and secreted. In the control group, the inflammation of the vagina was not completely recovered until the 9th day. On the 5th day after treatment with probiotic-ginsenoside R1 self-assembled hydrogel, the inflammation of the vulvar area was greatly reduced, and the vaginal secretion was almost negligible, and the redness and swelling almost disappeared. The therapeutic effect of probiotic-ginsenoside R1 self-assembled hydrogel was further evaluated by counting the number of colonies in the agar plates of the vaginal wash collected on the 1st, 3rd, 5th, 7th, and 9th days. As shown in FIG. 7B, compared with the control group, the cell viability and colony formation of Candida albicans treated with probiotic-ginsenoside R1 self-assembled hydrogel and itraconazole were significantly reduced.

[0095] In addition, pathological evaluation after H&E and high-iodide (PAS) staining was also performed (FIG. 7C), and the vaginal epithelium treated with probiotic-ginsenoside R1 self-assembled hydrogel maintained a smooth endometrial morphology without obvious irregularities. In contrast, the keratinized layer of the vaginal mucosal epithelium of the control group mice was significantly damaged, and a large number of neutrophils were obviously visible in the interstitium due to fungal infection and inflammatory cells infiltration, indicating that inflammation still existed in the body of these mice.

[0096] In order to detect the fungal residues on the infected tissues of the mice on the 5th day, polysaccharides were stained using PAS staining method (FIG. 7D). After treatment with probiotic-ginsenoside R1 self-assembled hydrogel, the amount of fungal residues on the vaginal tissue was almost the same as that on the uninfected tissue, while the infection of the other groups was still obvious.

[0097] The above experimental results prove that probiotic-ginsenoside R1 self-assembled hydrogel has excellent therapeutic effect on candidal vaginitis.

[0098] 4.3 Evaluation of the remodeling effect of ginger-like notoginsenoside R1 self-assembled hydrogel probiotic delivery system on vaginal microecology

[0099] There is evidence that the vaginal microecology of patients with candidal vaginitis is disordered, characterized by reduced biodiversity, decreased proportion of Firmicutes, and increased proportion of Proteobacteria. Lactic acid bacteria promote the stability of the vaginal environment, prevent the settlement and growth of harmful microorganisms, and regulate the ecological balance of the vagina. Therefore, we performed 16S rDNA sequencing on vaginal wash samples from mice at the end of treatment to investigate whether probiotic- ginger-like notoginsenoside R1 self-assembled hydrogel treatment was better than itraconazole treatment in regulating the composition of the mouse vaginal microbiota. Analysis showed that compared with the traditional antifungal drug itraconazole, probiotic- ginger-like notoginsenoside R1 self-assembled hydrogel treatment improved the alpha diversity of the vaginal microecology of mice with candidal vaginitis (P < 0.05) (Fig. 8A). FIG. 8A ).

[0100] PCoA (principal co-ordinates analysis) showed that after probiotic- ginger-like notoginsenoside R1 self-assembled hydrogel treatment, the vaginal microecology of mice with candidal vaginitis was most similar to that of the blank group and was significantly different from that of the itraconazole group, suggesting that the ginger-like notoginsenoside R1 self-assembled hydrogel probiotic delivery system can effectively remodel the healthy vaginal microenvironment and is expected to treat and prevent recurrent vaginitis (Fig. 8B).

[0101] The applicant states that the process of the present application is illustrated by the above examples, but the present application is not limited to the above process steps, nor does it mean that the present application must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvement on the present application, equivalent replacement of the materials selected by the present application, addition of auxiliary ingredients, selection of specific methods, etc. fall within the scope of protection and disclosure of the present application.

Claims

1. A self-assembling hydrogel, characterized in that, The self-assembled hydrogel is a hydrogel prepared by using a phosphate buffer and notoginseng saponin R1, and the concentration of notoginseng saponin R1 in the self-assembled hydrogel is 1.5-2.5 wt%; The preparation method of the self-assembled hydrogel is: dispersing notoginseng saponin R1 in a phosphate buffer and heating, and then cooling to obtain the self-assembled hydrogel.

2. The self-assembling hydrogel of claim 1, wherein, The pH of the phosphate buffer is 7-8.

3. The self-assembling hydrogel of claim 2, wherein, The pH of the phosphate buffer is 7.4, and the concentration of the phosphate buffer is 0.01M.

4. Use of the self-assembled hydrogel according to any one of claims 1-3 for preparing a drug carrier.

5. Use according to claim 4, characterized in that, The active pharmaceutical ingredient carried by the drug carrier is one or more of probiotics, antibiotics, and natural products.

6. Use according to claim 5, characterized in that, The probiotics are one or more of Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium, Lactobacillus acidophilus, and Escherichia coli Nissle 1917. The antibiotic is doxorubicin. The natural product is one or more of curcumin, berberine, and rhein.

7. A medicament, characterized by comprising a compound of the formula (I) or a pharmaceutically acceptable salt thereof. The self-assembled hydrogel according to any one of claims 1-3 and the active pharmaceutical ingredient coated in the self-assembled hydrogel.

8. The medicament according to claim 7, characterized in that, The active pharmaceutical ingredient is one or more of probiotics, antibiotics, and natural products; the probiotics are one or more of Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium, Lactobacillus acidophilus, and Escherichia coli Nissle 1917; the antibiotic is doxorubicin; and the natural product is one or more of curcumin, berberine, and rhein.

9. The medicament according to claim 8, characterized in that, The drug is an oral drug, a drug applied to the skin, or a drug directly placed in the vagina or the intestinal tract.

10. The medicament according to claim 9, characterized in that, The probiotics are Lactobacillus rhamnosus, and the drug is a drug for treating vaginitis.

11. The medicament according to claim 10, characterized in that, 1 x 10 6 ~1 x 10 10 CFUs Lactobacillus rhamnosus.

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