Self-assembled hydrogel as well as preparation method and application thereof

Abstract

The invention belongs to the field of medicines, and discloses a self-assembled hydrogel, and the self-assembled hydrogel is a hydrogel prepared from a phosphate buffer solution and zingiberaceae notoginsenoside R1. The self-assembled hydrogel disclosed by the invention has relatively good stability, viscoelasticity, biocompatibility and antibacterial ability, and can stably act on a tissue affected part in a self-healing manner independently or / and in a manner of carrying other medicines, so that the diagnosis and treatment effect is improved, and particularly the diagnosis and treatment effect on diseases based on antibacterial and anti-inflammatory requirements is improved. Meanwhile, the invention also provides a preparation method and application of the self-assembled hydrogel, especially application of the self-assembled hydrogel as a gel medicine for treating vaginitis.

Description

Technical Field

[0001] The present invention relates to the field of drugs, and particularly to a self-assembled hydrogel and its preparation method and use. Background Art

[0002] Panax zingiberensis refers to the roots and rhizomes of the perennial herb Panax zingiberensis C.Y.Wu et K.M.Feng of the genus Panax in the family Araliaceae, and is a traditional Chinese medicine with important medicinal value. "Chinese Herbal Medicine" summarizes that both the roots and leaves of Panax zingiberensis can be used as medicine. Zingibroside R1 is a natural triterpenoid saponin and one of the main active ingredients of Panax notoginseng and Panax zingiberensis, showing anti-tumor effects and anti-angiogenic activities, and having high value in medical treatment and commerce. However, the biomedical activities of zingibroside R1 have 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 required to improve its bioavailability when used, and the introduction of a delivery carrier or adjuvant may bring unpredictable side effects, limiting its clinical application.

[0003] The following patent literatures regarding the related applications of zingibroside R1 or notoginsenoside R1 can be found:

[0004] Publication No. CN118340721A, a patent application on the ophthalmic gel preparation of total saponins of Panax notoginseng and its preparation method and use, which records the use of a thickener to form a gel system for delivering notoginsenosides, and the notoginsenosides include notoginsenoside R1.

[0005] Publication No. CN117258051A, a patent application on a medical hydrogel composition, a medical hydrogel and its preparation method and application, which records the delivery of notoginsenoside R1 by loading it on a carrier.

[0006] Due to the problems of the solubility and bioavailability of zingibroside R1, a large amount of cross-linking agents or preservatives have been used in previous studies to deliver notoginsenoside R1. Therefore, those skilled in the art have made various improvements in how to load and release notoginsenosides.

[0007] Therefore, the present invention attempts to conduct in-depth research on zingibroside R1 from the opposite direction to solve some of its inherent problems. Summary of the Invention

[0008] The object of the present invention is to provide a self-assembled hydrogel. Through in-depth research on notoginsenoside R1, it is found that after gelation in an aqueous solution, the gel can have good stability, viscoelasticity, biocompatibility and antibacterial ability, which means that the gel can stably act on the affected tissue alone or in the form of carrying other drugs in a self-healing manner, improving the diagnosis and treatment effect, especially for diseases with antibacterial and anti-inflammatory requirements.

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

[0010] To achieve the above object, the present application discloses:

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

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

[0013] In the above self-assembled hydrogel, the self-assembled hydrogel does not contain any cross-linking agents, preservatives or other organic compounds; the solvent is a phosphate buffer solution (PBS); the pH of the phosphate buffer solution is 7-8, preferably, the pH of the phosphate buffer solution is 7.4, and the concentration of the phosphate buffer solution is 0.01 M, that is, 1×PBS.

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

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

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

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

[0018] In the above use, the drug active ingredient carried by the drug carrier is one or more of probiotics, antibiotics, and natural products.

[0019] In the above 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, and chlortetracycline;

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

[0022] Finally, the present invention also discloses a drug, which comprises the self-assembled hydrogel described above and a drug active ingredient encapsulated in the self-assembled hydrogel.

[0023] In the above drug, the drug active 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 one or more of doxorubicin, 5-fluorouracil, and chlortetracycline; the natural product is one or more of curcumin, berberine, and rhein.

[0024] In the above drug, the drug is an oral drug, a drug applied externally to the skin, or a drug directly placed in the vagina or intestine.

[0025] In the above drug, the probiotic is Lactobacillus rhamnosus, and the drug is a drug for treating vaginitis.

[0026] In the above drug, each milliliter of the self-assembled hydrogel loads 1×10 6 ~1×10 10 CFUs of Lactobacillus rhamnosus.

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

[0028] 1. The notoginsenoside R1 self-assembled hydrogel of the present invention has good stability, viscoelasticity, biocompatibility, and antibacterial ability, which means that the gel can stably act on the tissue affected area alone or in combination with other drugs in a self-healing manner, improving the diagnosis and treatment effect, especially for diseases requiring antibacterial and anti-inflammatory treatment.

[0029] 2. When the notoginsenoside R1 self-assembled hydrogel of the present invention is used in combination with other drug active ingredients in the form of a drug carrier, it has a 100% drug loading rate and slow drug release characteristics.

[0030] In a more specific application scenario of the present invention, the notoginsenoside R1 self-assembled hydrogel can effectively treat vaginitis by carrying probiotics and using the method of local vaginal administration. It does not disrupt the vaginal microecology, has excellent viscoelasticity, can effectively reduce the mechanical friction between tissues during implantation, helps to reduce the discomfort that patients may feel during the administration process. It can not only serve as a probiotic delivery carrier but also exert its own efficacy in killing Candida albicans. The two form a synergistic treatment, complementing each other, and can not only relieve symptoms, reduce recurrence, but also reshape a healthy vaginal microenvironment. Description of the Drawings

[0031] Figure 1A It is a schematic diagram of the gelation process of the notoginsenoside R1 self-assembled hydrogel;

[0032] Figure 1B It is a gel formation photo of the notoginsenoside R1 self-assembled hydrogel with different concentrations;

[0033] Figure 1C It is an X-ray diffraction pattern of the notoginsenoside R1 self-assembled hydrogel;

[0034] Figure 1D It is a Fourier transform infrared spectrum of the notoginsenoside R1 self-assembled hydrogel;

[0035] Figure 1E It is a Zeta potential map of the notoginsenoside R1 self-assembled hydrogel;

[0036] Figure 2A It is an oscillation mode-frequency scan result graph of the notoginsenoside R1 self-assembled hydrogel;

[0037] Figure 2B It is an oscillation mode-amplitude scan result graph of the notoginsenoside R1 self-assembled hydrogel;

[0038] Figure 2C It is a continuous time strain scan result graph of the notoginsenoside R1 self-assembled hydrogel;

[0039] Figure 3 It is a biocompatibility test result chart of the notoginsenoside R1 self-assembled hydrogel;

[0040] Figure 4 It is a photo of the adhesion ability test result of the notoginsenoside R1 self-assembled hydrogel;

[0041] Figure 5A It is a photo of the inhibitory ability of the notoginsenoside R1 self-assembled hydrogel against Candida albicans;

[0042] Figure 5BChart of the inhibitory ability of notoginsenoside R1 self-assembled hydrogel against Candida albicans;

[0043] Figure 6 Confocal images of probiotics encapsulated in notoginsenoside R1 self-assembled hydrogel.

[0044] Figure 7A Progress photos of the treatment of murine candidal vaginitis in each experimental group;

[0045] Figure 7B Chart of the progress of the treatment of murine candidal vaginitis in each experimental group;

[0046] Figure 7C Pathological evaluation photos of the treatment of murine candidal vaginitis in each experimental group;

[0047] Figure 7D Photos of fungal residues on the infected tissues of murine candidal vaginitis treated in each experimental group;

[0048] Figure 8A Result chart of the composition of the vaginal microbiota of mice after the treatment of murine candidal vaginitis in each experimental group;

[0049] Figure 8B Result chart of the PCoA principal coordinate analysis of the vaginal microecology after the treatment of murine candidal vaginitis in each experimental group.

[0050] Detailed Description of the Embodiments

[0051] The following will clearly and completely describe the present invention in combination with the embodiments of the present invention. In the description of the present invention, it should be noted that for those not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are followed. For the reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0052] The First Part: Source and Description of Raw Materials

[0053] The "notoginsenoside R1" mentioned in the embodiments has a white powder appearance, and the molecular formula is C 42 H 66 O 14 .

[0054] The molecular structural formula of notoginsenoside R1 involved in the present invention is:

[0055]

[0056] All animal experiments in the embodiments have been reviewed by the Life and Medical Ethics Review Committee of Hunan University. Unless otherwise specified, the probiotics used in animal experiments are all Lactobacillus rhamnosus, with a concentration of 1×10 9CFU / mL, derived from BNCC187896.

[0057] Part II Preparation and Characterization of Notoginsenoside R1 Self-Assembled Hydrogel

[0058] Example 1

[0059] Accurately weigh 3.00 mg of notoginsenoside R1 powder and place it in 200 μL of 1×PBS. Vortex and ultrasonically mix thoroughly, then heat in an oil bath at 100 °C for 60 min and cool naturally to obtain a 1.5% (w / w) notoginsenoside R1 self-assembled hydrogel.

[0060] Example 2

[0061] Accurately weigh 4.00 mg of notoginsenoside R1 powder and place it in 200 μL of 1×PBS. Vortex and ultrasonically mix thoroughly, then heat in an oil bath at 100 °C for 60 min and cool naturally to obtain a 2% (w / w) notoginsenoside R1 self-assembled hydrogel.

[0062] Example 3

[0063] Accurately weigh 5.00 mg of notoginsenoside R1 powder and place it in 200 μL of 1×PBS. Vortex and ultrasonically mix thoroughly, then heat in an oil bath at 100 °C for 60 min and cool naturally to obtain a 2.5% (w / w) notoginsenoside R1 self-assembled hydrogel.

[0064] The hydrogels of the above Examples 1 to 3 can maintain a stable hydrogel state visually. Photos of each sample are referred to Figure 1B .

[0065] Comparative Example 1

[0066] Accurately weigh 4.00 mg of notoginsenoside R1 powder and place it in 200 μL of physiological saline. Vortex and ultrasonically mix thoroughly, then heat in an oil bath at 95 °C for 60 min and cool naturally. It is found that it cannot form a hydrogel.

[0067] It can be seen from the above Examples 1 to 3 and Comparative Example 2 that the necessary condition for notoginsenoside R1 to form a gel is to be dispersed in PBS solution.

[0068] Continue the subsequent tests on the 2 wt% hydrogel of Example 2 above.

[0069] Part III Performance Test of Notoginsenoside R1 Self-Assembled Hydrogel

[0070] 3.1 Stability Characterization of Notoginsenoside R1 Self-Assembled Hydrogel

[0071] The gelation processes of the hydrogels of Examples 1 - 3 are asFigure 1A as shown

[0072] The gelation photos of self-assembled hydrogels of notoginsenoside R1 at different concentrations in Examples 1-3 are as Figure 1B shown

[0073] Subsequently, X-ray diffraction (XRD) analysis and Fourier Transform Infrared spectroscopy (FTIR) analysis were performed on the freeze-dried powder of the gel, and Zeta potential analysis was performed on the gel. The results are respectively as Figures 1B to 1D shown

[0074] Compared with notoginsenoside R1 powder (ZR1), the diffraction peaks of self-assembled hydrogel of notoginsenoside R1 (ZR1 gel) are obvious, showing a crystalline structure with ordered molecular arrangement; the FTIR spectrum shows enhanced O-H stretching vibration and red shift of asymmetric and symmetric C=O stretching vibrations of carboxyl groups, indicating that hydrogen bonds are involved in the assembly process of self-assembled hydrogel of notoginsenoside R1; in addition, the zeta potential of self-assembled hydrogel of notoginsenoside R1 is -38.3±0.47 mV, indicating that the stability of self-assembled hydrogel of notoginsenoside R1 is improved compared with the solution phase.

[0075] 3.2 Viscoelastic characterization of self-assembled hydrogel of notoginsenoside R1

[0076] This experiment was carried out using an Anton Par MCR-92 system (Austria) rotational rheometer to perform dynamic and static viscoelastic tests on the self-assembled hydrogel of notoginsenoside R1.

[0077] The test temperature of the sample was 37 °C, the test gap was 1 mm, and a thin layer of silicone oil was applied to the edge of the contact surface between the rotor and the sample. The test parameters for different scanning modes were set as follows: ① Oscillation mode - frequency sweep: the angular frequency range was 0.1-100 rad / s, varying logarithmically, and the strain value γ was a constant 0.2%; ② Oscillation mode - amplitude sweep: the shear strain γ was set to vary logarithmically from the initial value to the final value of 0.1%-100%, and the angular frequency value was a constant value of 6 rad / s; ③ Continuous time strain sweep: first collect 25 data points at 0.2% Strain, then collect 5 data points at 500% Strain and then collect 25 data points at 0.2% Strain, the pressure change cycle was repeated three times, and the sample was tested three times or more.

[0078] The test results are shown in Figure 2. In the oscillatory mode - frequency sweep, the storage modulus (G’) of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. was always greater than the loss modulus (G”), showing no frequency dependence, which proved that the sample was in a gel state and had good stability; in the oscillatory mode - amplitude sweep, when the shear strain γ reached 13%, the storage modulus (G’) of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. was equal to the loss modulus (G”), indicating that it showed good balance performance and stability under shear conditions; in the further continuous strain step sweep, after multiple 0.2% - 500% strain cycles, the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. could still return to its original state, proving that the sample had excellent self - healing ability.

[0079] 3.3 Biocompatibility of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc.

[0080] After incubating the Caco - 2 cell line with the self - assembled hydrogels of notoginsenoside R1 from Zingiber officinale Rosc. with mass fractions of 1.5%, 2% and 2.5% for 6 hours, 12 hours or 24 hours respectively, the cell viability of Caco - 2 was measured using the MTT assay, and the experiment was repeated three times. The experimental results are as Figure 3 shown. The self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. has good biocompatibility and does not produce obvious cytotoxicity to epithelial - like cells when incubated for 24 hours at a mass fraction of 2%.

[0081] 3.4 Determination of the tissue adhesion ability of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc.

[0082] 200 μL of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. was evenly spread on the fitting part of a fresh pigskin (with an area of about 10 cm 2 ), and then another piece of pigskin was partially covered on the hydrogel - spread part and left standing for a while. One end of the joined pigskins was picked up with forceps, and different weights were hung at the other end to test the adhesion of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc.

[0083] The experimental results are as Figure 4 shown. The fresh pigskins joined together after spreading the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. could bear a weight of 40 g, indicating that the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc. has the ability to adhere to tissues.

[0084] 3.5 Determination of the antibacterial performance of the self - assembled hydrogel of notoginsenoside R1 from Zingiber officinale Rosc.

[0085] The cryopreserved Candida albicans (CA) was inoculated into SDS liquid medium and cultured in a shaking incubator at 37 °C for 12 h to revive the fungal viability. After centrifuging to remove the supernatant medium, it was adjusted to OD 630= 0.6. Similarly, prepare 2% notoginsenoside R1 self-assembled hydrogel for later use. Experimental group: Take 200 μL of the culture medium containing Candida albicans with OD 630 = 0.6 and add it to a shaking tube. Subsequently, add the freeze-dried powder of notoginsenoside R1 self-assembled hydrogel to the shaking tube to make its mass fraction 2%, and incubate for 2 h. Control group: Take 200 μL of the culture medium containing Candida albicans with OD 630 = 0.6 and add it to a shaking tube, without any treatment, and incubate for 2 h. After incubation, dilute it by 10 7 times, then take 20 μL and spread it on the SDS solid medium. Finally, place it in an incubator at 37 °C and wait for it to grow. Finally, count the colonies growing on it. The experiment was repeated three times.

[0086] The antibacterial ability of notoginsenoside R1 gel against Candida albicans was evaluated by the plate counting method. The results are as Figure 5A and Figure 5B shown. Notoginsenoside R1 gel can significantly inhibit the activity of Candida albicans.

[0087] Part 4 Preparation and performance characterization of notoginsenoside R1 self-assembled hydrogel encapsulating probiotics

[0088] 4.1 Detection of probiotic encapsulation and co-localization in notoginsenoside R1 self-assembled hydrogel

[0089] Encapsulate the notoginsenoside R1 self-assembled hydrogel in Example 2 with probiotics. The preparation method is as follows:

[0090] Mix 2% notoginsenoside R1 solution with congo red dye, then heat it in an oil bath at 100 °C for 60 min, naturally cool it to 37 °C, encapsulate 10 10 fluorescent EcN-GFP probiotics, continue to naturally cool to form a gel, and use a laser confocal fluorescence microscope to observe the co-localization of probiotics and hydrogel.

[0091] Mix notoginsenoside R1 self-assembled hydrogel with probiotics, freeze-dry it, and use a scanning electron microscope to observe the co-localization of probiotics and hydrogel.

[0092] The experimental results are as Figure 6 shown. Both the laser confocal microscope and the scanning electron microscope observed that the probiotics were encapsulated in the notoginsenoside R1 self-assembled hydrogel.

[0093] 4.2 Evaluation of the therapeutic effect of notoginsenoside R1 self-assembled hydrogel probiotic delivery system on a mouse model of vaginitis

[0094] Thirty purchased mice were divided into six 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, with five mice in each group. First, a mouse model of candidal vaginitis was constructed: The mice in the experimental groups (groups ②-⑥) were intraperitoneally injected with 100 μL of estradiol benzoate (2 mg / mL) every day for six days, and then Candida albicans suspension (20 μL / mouse, OD 630 = 0.6) was intravaginally perfused into the mice in the experimental groups for six days. After the modeling, drugs were administered according to the groups for nine days. During this period, 100 μL of vaginal lavage fluid was collected from each group of mice and stored in a -80 °C refrigerator. When needed, it was plated for counting, and the daily body weight changes and vaginal appearance of each group of mice were recorded. After the treatment, the mice were sacrificed, and the vaginal tissues were dissected for pathological analysis.

[0095] As Figure 7A shown, on the first day of Candida albicans infection, the vaginas of all mice in the experimental groups showed redness and secretions. In the control group, vaginal inflammation did not completely improve until the ninth day. On the fifth day after treatment with the probiotic-ginsenoside R1 self-assembled hydrogel, the inflammation in the vulvar area was greatly reduced, the vaginal secretions were almost negligible, and the swelling and redness almost disappeared. The therapeutic effect of the probiotic-ginsenoside R1 self-assembled hydrogel was further evaluated by calculating the colony counts in the vaginal lavage agar plates collected on the 1st, 3rd, 5th, 7th, and 9th days. As Figure 7B shown, compared with the control group, the cell viability and colony formation of Candida albicans treated with the probiotic-ginsenoside R1 self-assembled hydrogel and itraconazole were significantly reduced.

[0096] In addition, pathological evaluations after H&E and periodic acid-schiff (PAS) staining ( Figure 7C ) were also performed. The vaginal epithelium treated with the probiotic-ginsenoside R1 self-assembled hydrogel maintained a smooth endometrial morphology without obvious irregularities. In contrast, the keratinized layer of the vaginal mucosal epithelium in the control group mice was significantly damaged, and a large number of neutrophils were significantly infiltrated in the stroma due to fungal infection and inflammatory cells, indicating that there was still inflammation in these mice.

[0097] To detect the fungal residues on the infected tissues of mice on the fifth day, polysaccharides were stained using the PAS staining method ( Figure 7D ). After treatment with the probiotic-ginsenoside R1 self-assembled hydrogel, the amount of fungal residues on the vaginal tissues was almost the same as that on the uninfected tissues, while the infections in the other groups were still obvious.

[0098] The above experimental results demonstrated that the probiotic-ginsenoside R1 self-assembled hydrogel has excellent therapeutic effects on candidal vaginitis.

[0099] 4.3 Evaluation of the Remodeling Effect of the Self-Assembled Hydrogel Probiotic Delivery System of Notoginsenoside R1 on the Vaginal Microbiota

[0100] There is evidence that the vaginal microbiota of patients with vulvovaginal candidiasis is disrupted, characterized by reduced biodiversity, a decreased proportion of Firmicutes organisms, and an increase in Proteobacteria organisms. Lactobacilli 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 the probiotic - notoginsenoside R1 self-assembled hydrogel treatment better regulates the composition of the vaginal microbiota in mice than itraconazole treatment. The analysis showed that compared with the traditional antifungal drug itraconazole, the treatment with the probiotic - notoginsenoside R1 self-assembled hydrogel improved the alpha diversity of the vaginal microbiota in mice with vulvovaginal candidiasis ( Figure 8A ).

[0101] Principal co-ordinates analysis (PCoA) indicated that after treatment with the probiotic - notoginsenoside R1 self-assembled hydrogel, the vaginal microbiota of mice with vulvovaginal candidiasis was most similar to that of the blank group and significantly different from that of the itraconazole group, suggesting that the self-assembled hydrogel probiotic delivery system of notoginsenoside R1 can effectively remodel a healthy vaginal microenvironment and has the potential to treat and prevent recurrent vaginitis ( Figure 8B ).

[0102] The applicant declares that the process method of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above process steps, nor does it mean that the present invention must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvement to the present invention, equivalent substitution of the raw materials selected for the present invention, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A self-assembled hydrogel, characterized in that, The self-assembled hydrogel is a hydrogel prepared from phosphate buffer solution and notoginsenoside R1 of Zingiber officinale Rosc.

2. The self-assembled hydrogel according to claim 1, wherein The concentration of notoginsenoside R1 in the self-assembled hydrogel is 1.5 - 2.5 wt%.

3. The self-assembled hydrogel according to claim 1, wherein The pH of the phosphate buffer solution is 7 - 8. Preferably, the pH of the phosphate buffer solution is 7.4 and the concentration of the phosphate buffer solution is 0.01 M.

4. The preparation method of the self-assembled hydrogel according to any one of claims 1 to 3, characterized in that, The method is as follows: disperse notoginsenoside R1 in the phosphate buffer solution, mix it with water under heating conditions, and then cool to obtain the self-assembled hydrogel.

5. The preparation method according to claim 4, characterized in that, The heating temperature is 90 - 100 °C and the heating time is 30 - 90 min.

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

7. The use according to claim 6, wherein The drug active ingredient carried by the drug carrier is one or more of probiotics, antibiotics, and natural products.

8. The use according to claim 7, characterized in that, The probiotics are one or more of Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium, Lactobacillus acidophilus, and Escherichia coli Nissle 1917; The antibiotics are one or more of doxorubicin, 5-fluorouracil, and chlortetracycline; The natural products are one or more of curcumin, berberine, and rhein.

9. A drug, characterized in that, It includes the self-assembled hydrogel according to any one of claims 1 - 3 and the drug active ingredient encapsulated in the self-assembled hydrogel.

10. The drug according to claim 9, characterized in that, The drug active 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 antibiotics are one or more of doxorubicin, 5-fluorouracil, and chlortetracycline; the natural products are one or more of curcumin, berberine, and rhein.

11. The drug according to claim 9, characterized in that, The drug is an oral drug, a drug applied externally to the skin, or a drug directly placed in the vagina or intestine.

12. The medicament according to claim 10, wherein, The probiotic is Lactobacillus rhamnosus and the drug is a drug for treating vaginitis.

13. The drug according to claim 12, characterized in that, Each milliliter of the self-assembled hydrogel is loaded with 1x10 6 ~1x10 10 CFUs of Lactobacillus rhamnosus.

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