Injectable hydrogel for pet endometritis as well as preparation method and application of injectable hydrogel

Abstract

The invention provides injectable hydrogel for pet endometritis, and belongs to the technical field of veterinary drug preparation. The injectable hydrogel prepared by the invention is prepared from the following raw materials: forsythiaside A, chitosan, beta-sodium glycerophosphate, sodium hyaluronate, acetic acid and water. By combining the technical advantages of a temperature-sensitive gel technology and an injectable gel technology, forsythiaside A and chitosan are combined for use, so that the injectable hydrogel with excellent antibacterial performance is obtained. The forsythiaside A is wrapped by the chitosan, so that the antibacterial effect of the forsythiaside A is enhanced, the release time of the medicine is prolonged, the time required for repairing the inflammatory injury can be effectively shortened, and the probability of secondary infection in the uterine cavity is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of veterinary drug preparation, and in particular to an injectable hydrogel for pet endometritis and a preparation method and application thereof. Background Art

[0002] Endometritis is a disease in which the endometrium and myometrium produce severe inflammatory reactions, and is one of the main diseases that lead to decreased reproductive performance in female livestock. The etiology of this disease is complex, and infection by pathogenic microorganisms is one of its main causes, among which Escherichia coli and Staphylococcus aureus are the main pathogens of endometritis. The invasion of pathogenic microorganisms causes inflammatory reactions in the endometrium and myometrium, resulting in damage to the endometrium, which in turn leads to reproductive disorders.

[0003] At present, local or systemic administration of antibiotics is a commonly used clinical treatment for endometritis, but there are problems such as easy drug resistance, high drug residue and large toxic side effects. For example, Chinese patent CN117717520A discloses a method for preparing a novel uterine injection, wherein the injection prepared uses cephalosporin antibiotic ceftiofur crystalline free acid as the main drug component, and specifically includes the following raw materials: ceftiofur crystalline free acid 5-10%; emulsifier: 5-10%; oil: 5-10%; calcium silicate 6-10%; hydrophilic silicon dioxide 3-5%; modified sesbania powder 5-10%, surfactant 2-5%; antioxidant 1-3%; injection matrix 37-68%.

[0004] Therefore, it is urgent to develop new drug preparations to replace antibiotics for the treatment of endometritis. Plant-derived drugs are not easy to develop drug resistance, have low drug residues and few toxic side effects. Among them, the active ingredient of plant-derived drugs, forsythiaside A, has antibacterial and anti-inflammatory pharmacological effects, but it is still not widely used in the treatment of veterinary clinical diseases due to the restrictions of administration methods, preparation processes and drug utilization.

[0005] The medicinal part of Forsythia suspensa is its dried fruit, which has the effect of clearing away heat and detoxifying, and has been widely used in the prevention and treatment of diseases such as acute nephritis, erysipelas, and ulcers. Forsythia suspensa has a wide range of pharmacological effects. Forsythia glycoside A is a phenylethanol glycoside compound extracted from the dried fruit of Forsythia suspensa. As one of the main components of Forsythia suspensa, it has antibacterial, antioxidant, and antiviral effects. Many studies have shown that Forsythia glycoside A, as one of the strongest antibacterial components in Forsythia suspensa, can effectively inhibit Staphylococcus aureus and achieve anti-inflammatory and anti-infection effects.

[0006] Injectable hydrogels have excellent biocompatibility, good permeability, and low invasiveness, so they have superior benefits compared to traditional hydrogels. For example, the use of injectable hydrogels does not require complex surgical procedures. Injectable hydrogels can ultimately reduce the discomfort and treatment costs of pets through simple and minimally invasive procedures.

[0007] How to prepare an injectable hydrogel using forsythiaside A, an active ingredient of plant-derived medicine, as raw material is the problem to be solved at present. Summary of the invention

[0008] In order to solve the above problems, the purpose of the present invention is to provide an injectable hydrogel for pet endometritis. The present invention encapsulates Forsythiaside A by chitosan, and improves the antibacterial property of Forsythiaside A by combining the antibacterial activity of chitosan, thereby obtaining an injectable hydrogel with excellent antibacterial property, which can reduce intrauterine infection, effectively shorten the repair time of inflammatory damage, and is convenient for vaginal administration.

[0009] In order to achieve the above object, the present invention provides the following technical solutions:

[0010] An injectable hydrogel for pet endometritis comprises the following raw materials in parts by weight:

[0011] 0.1-2 parts of forsythiaside A, 0.8-1.4 parts of chitosan, 9.5-15 parts of sodium β-glycerophosphate, 0.19-0.3 parts of sodium hyaluronate, 0.1-10 parts of acetic acid, and 50-100 parts of water.

[0012] Furthermore, the injectable hydrogel for pet endometritis comprises the following raw materials in parts by mass: 0.8 parts of forsythiaside A, 1.12 parts of chitosan, 14.4 parts of sodium β-glycerophosphate, 0.192 parts of sodium hyaluronate, 0.3 parts of acetic acid, and 81 parts of water.

[0013] Another object of the present invention is to provide a method for preparing an injectable hydrogel for pet endometritis, comprising the following steps:

[0014] (1) Weigh the raw materials according to the proportion;

[0015] (2) taking a portion of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0016] (3) taking a portion of the water, adding forsythiaside A thereto, stirring evenly, and dissolving by ultrasonication to obtain solution 2;

[0017] (4) adding sodium β-glycerophosphate and sodium hyaluronate to the remaining water and stirring evenly to obtain solution 3;

[0018] (5) adding solution 2 dropwise to solution 1 and stirring evenly to obtain solution 4;

[0019] (6) Add the solution 3 dropwise into the solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis.

[0020] Furthermore, in step (2), the mass ratio of chitosan to water is 0.02-0.03:1.

[0021] Furthermore, in step (3), the mass ratio of the forsythiaside A to water is 0.8-0.9:1.

[0022] Furthermore, the volume ratio of solution 1 to solution 3 is 6-8:2-4.

[0023] Furthermore, the temperature of the dropwise addition in step (5) is room temperature or an ice water bath.

[0024] Furthermore, before the dropwise addition in step (6), the solution 3 and the solution 4 are placed at 0 to 4° C. for 30 to 40 minutes;

[0025] Furthermore, the dropwise adding in step (6) is carried out in an ice water bath.

[0026] Furthermore, the dropping in step (6) requires stirring at a speed of 1000 to 1200 r / min.

[0027] The third object of the present invention is to provide an injectable hydrogel for pet endometritis for use in the preparation of antibacterial and anti-inflammatory drugs.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention provides an injectable hydrogel for pet endometritis, which combines the technical advantages of thermosensitive gel technology and injectable gel technology, and uses forsythiaside A and chitosan together to obtain an injectable hydrogel with excellent antibacterial properties. In particular, forsythiaside A is wrapped with chitosan to enhance its antibacterial effect and reduce the probability of secondary infection in the uterine cavity. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a diagram showing the appearance changes of the injectable hydrogel for pet endometritis prepared in Example 1 of the present invention;

[0031] Figure 2 This is a scanning electron micrograph of the injectable hydrogel for pet endometritis prepared in Example 1 of the present invention;

[0032] Figure 3 This is a particle size diagram of the injectable hydrogel for pet endometritis prepared in Example 1 of the present invention;

[0033] Figure 4 This is a Zeta potential diagram of the injectable hydrogel for pet endometritis prepared in Example 1 of the present invention;

[0034] Figure 5 This is a diagram showing the antibacterial effect of an injectable hydrogel for pet endometritis prepared in Example 1 of the present invention;

[0035] Figure 6 The results of HE staining of uterine tissue of mice in different treatment groups. DETAILED DESCRIPTION

[0036] The present invention is further described below with reference to the embodiments, in which the “parts” described in the following embodiments are all “parts by mass”.

[0037] Example 1

[0038] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0039] 0.8 parts of forsythiaside A (original drug), 1.12 parts of chitosan, 14.4 parts of sodium β-glycerophosphate, 0.192 parts of sodium hyaluronate, 0.3 parts of acetic acid, and 81 parts of water.

[0040] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0041] (1) Weigh the raw materials according to the proportion;

[0042] (2) taking 56 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0043] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0044] (4) Add sodium β-glycerophosphate and sodium hyaluronate to the remaining water and stir evenly to obtain solution 3; (the volume ratio of chitosan solution to sodium β-glycerophosphate / sodium hyaluronate solution is 7:3)

[0045] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0046] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0047] Example 2

[0048] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0049] 0.8 parts of forsythiaside A (original drug), 1.28 parts of chitosan, 9.6 parts of sodium β-glycerophosphate, 0.128 parts of sodium hyaluronate, 0.3 parts of acetic acid, and 81 parts of water.

[0050] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0051] (1) Weigh the raw materials according to the proportion;

[0052] (2) taking 64 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0053] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0054] (4) adding sodium β-glycerophosphate and sodium hyaluronate to the remaining water and stirring evenly to obtain solution 3 (wherein the volume ratio of the chitosan solution to the sodium β-glycerophosphate / sodium hyaluronate solution is 8:2);

[0055] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0056] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0057] Example 3

[0058] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0059] 0.8 parts of forsythiaside A (original drug), 0.96 parts of chitosan, 19.2 parts of sodium β-glycerophosphate, 0.192 parts of sodium hyaluronate, 0.3 parts of acetic acid, and 81 parts of water.

[0060] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0061] (1) Weigh the raw materials according to the proportion;

[0062] (2) taking 48 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0063] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0064] (4) adding sodium β-glycerophosphate and sodium hyaluronate to the remaining water and stirring evenly to obtain solution 3 (wherein the volume ratio of the chitosan solution to the sodium β-glycerophosphate / sodium hyaluronate solution is 6:4);

[0065] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0066] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0067] The "inversion method" was used to detect the temperature sensitivity of the injectable hydrogels prepared in Examples 1 to 3. 3 mL of the prepared injectable hydrogel was put into a glass bottle and placed in a 37°C constant temperature water bath. The fluidity of the liquid was observed while timing. When the fluidity became low, the glass bottle was taken out every 30 seconds and inverted 180°. If the sample did not flow for 30 seconds, it indicated that the liquid had turned into gel, and the gelation time was recorded. The results are shown in Table 1.

[0068] Table 1

[0069]

[0070] Comparative Example 1

[0071] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0072] 0.8 parts of Forsythiaside A (original drug), 1.12 parts of chitosan, 14.4 parts of sodium β-glycerophosphate, 0.3 parts of acetic acid, and 81 parts of water.

[0073] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0074] (1) Weigh the raw materials according to the proportion;

[0075] (2) taking 56 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0076] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0077] (4) adding sodium β-glycerophosphate to the remaining water and stirring evenly to obtain solution 3 (wherein the volume ratio of the chitosan solution to the sodium β-glycerophosphate solution is 7:3);

[0078] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0079] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0080] Comparative Example 2

[0081] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0082] 0.8 parts of Forsythiaside A (original drug), 1.28 parts of chitosan, 9.6 parts of sodium β-glycerophosphate, 0.3 parts of acetic acid, and 81 parts of water.

[0083] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0084] (1) Weigh the raw materials according to the proportion;

[0085] (2) taking 64 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0086] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0087] (4) adding sodium β-glycerophosphate to the remaining water and stirring evenly to obtain solution 3 (wherein the volume ratio of the chitosan solution to the sodium β-glycerophosphate solution is 8:2);

[0088] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0089] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0090] Comparative Example 3

[0091] An injectable hydrogel for endometritis in pets, comprising the following raw materials:

[0092] 0.8 parts of Forsythiaside A (original drug), 0.96 parts of chitosan, 19.2 parts of sodium β-glycerophosphate, 0.3 parts of acetic acid, and 81 parts of water.

[0093] The preparation method of the injectable hydrogel for pet endometritis comprises the following steps:

[0094] (1) Weigh the raw materials according to the proportion;

[0095] (2) taking 48 parts of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1;

[0096] (3) Take 1 part of water, add forsythiaside A thereto, stir evenly, and dissolve with ultrasound to obtain solution 2;

[0097] (4) adding sodium β-glycerophosphate to the remaining water and stirring evenly to obtain solution 3 (wherein the volume ratio of the chitosan solution to the sodium β-glycerophosphate solution is 6:4);

[0098] (5) adding solution 2 dropwise to solution 1 at room temperature and stirring evenly to obtain solution 4;

[0099] (6) Place solution 3 and solution 4 in an ice water bath for 40 minutes, then drop solution 3 into solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis. The composite gel contains a complex of forsythiaside A and chitosan.

[0100] The "inversion method" was used to detect its temperature sensitivity. 3 mL of the prepared injectable hydrogel was placed in a glass bottle and placed in a 37°C constant temperature water bath. The fluidity of the liquid was observed while timing. When the fluidity became low, the glass bottle was taken out every 30 seconds and inverted 180°. If the sample did not flow for 30 seconds, it means that the liquid has turned into gel, and the gelation time was recorded. The results are shown in Table 2.

[0101] Table 2

[0102]

[0103] The hydrogel prepared in Example 1 was subjected to the following characterization and experiments.

[0104] (I) Schematic diagram of the appearance change of the gel prepared in Example 1 at different temperatures Figure 1 .from Figure 1 It can be seen that the hydrogel prepared in Example 1 of the present invention is a brown-yellow sol-like state with uniform transparency, no drug precipitation, and can be transformed into a brown-yellow solid gel at body temperature (37° C.), which proves that after the hydrogel of the present invention is injected into the pet's uterus, it can quickly form a gel to cover the affected area and exert its effect.

[0105] (ii) After freeze-drying the gel sample prepared in Example 1 of the present invention, it was adhered to a scanning electron microscope sample plate with conductive glue, and gold was sputtered using an ion sputtering device. Then, the structure of the sample was observed using a scanning electron microscope. The results of the scanning electron microscope are shown in FIG. Figure 2 .from Figure 2It can be seen that the hydrogel prepared in Example 1 of the present invention forms a three-dimensional grid pore structure with uniform pore size, which can carry drugs well and facilitate the absorption and release of nutrients and metabolites.

[0106] (III) Take 1 mL of the hydrogel prepared in Example 1 of the present invention, dilute it 100 times with deionized water, sonicate for 30 min, and store it for later use. Use a nanoparticle size and Zeta potential analyzer (DLS) to measure the particle size and Zeta potential. The particle size measurement results are as follows: Figure 3 The Zeta potential measurement results are as follows Figure 4 .

[0107] from Figure 3 and Figure 4 It can be seen that the particle size of the gel prepared in Example 1 of the present invention is 4.248 nm ( Figure 3 ), due to the small particle size of the gel, the drug can be better delivered to the medication site through the tissue gap, thereby achieving the effect of antibacterial and promoting tissue repair; the Zeta potential is -22.5mV ( Figure 4 ), indicating that the surface charge is neutral and can be adsorbed on the bacterial surface to inhibit bacterial growth.

[0108] (IV) Observation of antibacterial effect by plate coating method

[0109] The hydrogel prepared in Example 1 of the present invention was formulated into a hydrogel with a drug loading concentration of 10 mg / mL. The constant dilution method was slightly modified. 0.1 g of the freeze-dried hydrogel powder prepared in Example 1 of the present invention was weighed and added to a shaking bottle containing 5 mL of autoclaved MH broth, and 1 mL of E. coli, S. aureus, SCVA (1×10 8 CFU / mL), and placed in a 37℃ constant temperature oscillator at 200r / min for 18-24h. The obtained bacterial suspension (100.0μL) was extracted onto a plate, and the coating was diluted by 10-fold dilution method. The diluted coating solution (100.0μL) was added to the nutrient agar medium. The plate was further cultured at 37℃ for 24 hours, and the antibacterial effect was obtained as shown in the figure. Figure 5 .

[0110] from Figure 5 It can be seen that the results of the pet-specific endometrial inflammatory injury injectable gel on the plate for E. coli single bacteria showed that a large number of colonies grew, and the antibacterial effect was poor; the results of the plate coating on the S. aureus single bacteria showed that a small number of colonies grew, showing an antibacterial effect; the results of the plate coating on the SCVA single bacteria showed that a large number of colonies grew, and the antibacterial effect was poor.

[0111] (V) Effect of injectable hydrogel for pet endometritis on the repair of endometrial inflammatory lesions in mice

[0112] Thirty-six healthy female Kunming mice (18-22g) were selected, and 0.2mL of 1mg / mL LPS was injected into the uterus from the vulva using a homemade uterine perfusion device to establish a mouse endometrial inflammatory injury model. After 12 hours, the mice showed depression, rough fur, and yellow secretions in the genitals, indicating that the model was successfully constructed. The mice were randomly divided into 4 groups (i.e., A. blank control group, B. LPS modeling group, C. injectable hydrogel treatment group for pet endometritis, and D. Forsythiaside A raw material drug treatment group) by random drawing, with 9 mice in each group. Group A did not receive any treatment, and the other 3 groups were modeled. After modeling, groups C and D were administered intrauterine with Forsythiaside A raw material drug solution and injectable hydrogel for pet endometritis, respectively, once every 24 hours, for a total of 4 times. 24 hours after the last administration, three mice were randomly selected from each group and anesthetized and then killed. The uterine tissue was removed and flattened on sterile filter paper. The blood on the tissue was cleaned and fixed with 4% paraformaldehyde. HE staining was performed. The HE staining results of the uterine tissue of mice in different treatment groups were obtained as follows: Figure 6 .

[0113] from Figure 6 It can be seen that the results of histopathological analysis showed that the uterine tissue structure of mice in the blank control group was normal, no inflammatory infiltration was found, the endometrial cells were closely arranged, and the glands were evenly distributed; the uterus of mice in the LPS modeling group showed obvious inflammatory cell infiltration, severe endometrial cell shedding, and destroyed glandular structure; after treatment with the Forsythiaside A raw material drug treatment group, the pathological changes in the uterine tissue of mice were significantly reduced, but a small amount of inflammatory cell infiltration and endometrial cell shedding were still visible; after treatment with the injectable hydrogel treatment group for pet endometritis, there was almost no obvious pathological change in the uterine tissue of mice.

[0114] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An injectable hydrogel for endometritis in pets, It is characterized in that Including the following raw materials by mass: 0.1-2 parts of forsythiaside A, 0.8-1.4 parts of chitosan, 9.5-15 parts of sodium β-glycerophosphate, 0.19-0.3 parts of sodium hyaluronate, 0.1-10 parts of acetic acid, and 50-100 parts of water.

2. The injectable hydrogel for pet endometritis according to claim 1, It is characterized in that The invention comprises the following raw materials in parts by weight: 0.8 parts of forsythiaside A, 1.12 parts of chitosan, 14.4 parts of sodium β-glycerophosphate, 0.192 parts of sodium hyaluronate, 0.3 parts of acetic acid and 81 parts of water.

3. The method for preparing the injectable hydrogel for pet endometritis according to claim 1 or 2, It is characterized in that The following steps are involved: (1) Weigh the raw materials according to the proportion; (2) taking a portion of water, adding chitosan thereto, and then adding acetic acid and stirring to dissolve, to obtain solution 1; (3) taking a portion of the water, adding forsythiaside A thereto, stirring evenly, and dissolving by ultrasonication to obtain solution 2; (4) adding sodium β-glycerophosphate and sodium hyaluronate to the remaining water and stirring evenly to obtain solution 3; (5) adding solution 2 dropwise to solution 1 and stirring evenly to obtain solution 4; (6) Add the solution 3 dropwise into the solution 4 and stir evenly to obtain the injectable hydrogel for pet endometritis.

4. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that The mass ratio of chitosan to water in step (2) is 0.02-0.03:

1.

5. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that The mass ratio of the forsythiaside A to water in step (3) is 0.8-0.9:

1.

6. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that The volume ratio of the solution 1 to the solution 3 is 6-8:2-4.

7. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that Before the dropwise addition in step (6), the solution 3 and the solution 4 are placed at 0 to 4° C. for 30 to 40 minutes.

8. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that The dropwise addition in step (6) is carried out in an ice-water bath.

9. The method for preparing the injectable hydrogel for pet endometritis according to claim 3, It is characterized in that The dropping in step (6) needs to be stirred at a speed of 1000 to 1200 r / min.

10. Use of the injectable hydrogel for pet endometritis according to claim 1 or 2, It is characterized in that The injectable hydrogel for pet endometritis is used in the preparation of antibacterial and anti-inflammatory drugs.

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