Temperature-sensitive poloxamer gel for preventing vaginal radiation injury and preparation method of temperature-sensitive poloxamer gel

Abstract

The invention provides temperature-sensitive poloxamer gel for preventing vaginal radiation injury and a preparation method of the temperature-sensitive poloxamer gel, and belongs to the technical field of medical gel. The temperature-sensitive type poloxamer gel is prepared from the following components: 6 percent to 18 percent of a poloxamer compound, 3 percent to 8 percent of a functional component, 0.01 percent to 0.08 percent of a penetration enhancer, 0.10 percent to 0.45 percent of a regulator, 0.13 percent to 0.25 percent of a humectant, 0.05 percent to 0.12 percent of a preservative and the balance of water, the poloxamer compound is prepared by compounding poloxamer 407 and poloxamer 188, and the poloxamer compound is prepared by compounding the poloxamer 407 and the poloxamer 188. The temperature-sensitive poloxamer gel for preventing the vaginal radiation injury, disclosed by the invention, is relatively long in retention time at an acting part, has a certain slow release effect, can keep long-time stimulation to vaginal mucosa, is beneficial to rapid healing of a wound surface, can effectively prevent radioactive vaginitis, is convenient to use, and is safe and non-irritant to a human body.

Description

Technical Field

[0001] This invention relates to the field of medical gel technology, specifically to a thermosensitive poloxamer gel for the prevention of vaginal radiation injury and its preparation method. Background Technology

[0002] Cervical cancer is one of the most common gynecological malignancies in women, ranking first among female reproductive tract malignancies in my country. In recent years, it has shown a trend of affecting younger women and an increasing incidence rate, posing a serious threat to women's lives and quality of life. Currently, the main treatments for cervical cancer are surgery and radiotherapy / chemotherapy. Radical radiotherapy is the preferred treatment for locally advanced cervical cancer, and it includes external beam radiation therapy and intracavitary brachytherapy, both of which are indispensable. However, when receiving brachytherapy, the radiation source is located in the cervix and vaginal area. The vagina and surrounding tissues are affected by ionizing radiation, making radiation vaginitis highly likely. Acute radiation vaginitis mainly manifests as vaginal mucosal congestion, edema, redness, pain, and unpleasant odor; chronic radiation vaginitis generally presents as vaginal adhesions or vaginal stenosis. These conditions not only cause significant inconvenience to patients' lives but also severely impact their self-confidence and quality of life. Therefore, early clinical intervention is of great significance for patients with vaginal radiation damage.

[0003] Currently, treatments for vaginal radiation damage mainly include vaginal washes, oral medications, and topical gels. However, vaginal washes kill not only pathogens but also vaginal lactobacilli and can easily disrupt the vaginal pH balance. Long-term use of vaginal washes can easily lead to a decrease in the body's immunity, increasing the risk of infection, and their effectiveness in preventing radiation damage caused by cervical cancer radiotherapy is not ideal. Currently, medications for treating vaginal radiation damage usually act on the affected area of ​​the vagina through blood circulation, but this treatment method has drawbacks such as slow onset of action, the need for long-term use, and significant side effects. Topical vaginal gels are commonly used to treat vaginal radiation damage, but they generally suffer from high irritation, easy allergies, and unsatisfactory treatment effects. Furthermore, most of the research published in this field focuses on the treatment of radiation vaginitis after its onset. Since radiation vaginitis has a long course and seriously affects patients' quality of life, providing a product to prevent vaginal radiation damage is particularly important.

[0004] Poloxamer 407 is an amphiphilic triblock copolymer composed of hydrophilic polyoxyethylene segments and hydrophobic polyoxypropylene segments in a specific ratio. It is a thermoresponsive copolymer with low viscosity at room temperature, transforming into a gel state upon reaching body temperature or elevated temperatures. It also exhibits excellent biocompatibility and biodegradability, making it an ideal thermosensitive gel material suitable for vaginal treatment. However, poloxamer 407 has poor adhesion, resulting in hydrogel materials with low mechanical strength and rapid dissolution. When diluted alone in a water-rich environment, poloxamer 407 gel quickly loses its gelling ability. Summary of the Invention

[0005] In view of this, the present invention provides a thermosensitive poloxamer gel for the prevention of vaginal radiation injury, comprising, by weight percentage, the following components:

[0006] The composition consists of 6%-18% poloxamer complex, 3%-8% functional ingredients, 0.01%-0.08% penetration enhancer, 0.10%-0.45% regulator, 0.13%-0.25% humectant, 0.05%-0.12% preservative, and the balance being water.

[0007] Furthermore, the poloxamer complex is composed of poloxamer 407 and poloxamer 188.

[0008] Furthermore, the mass ratio of poloxamer 407 to poloxamer 188 in the poloxamer complex is 15-45:3-12.

[0009] Furthermore, the functional ingredients include anti-inflammatory agents and repair agents, wherein the mass ratio of the anti-inflammatory agents to the repair agents is 3-8:10-17.

[0010] Furthermore, the preparation method of the anti-inflammatory agent includes: mixing dendrobine, resveratrol, guaiacol and anhydrous ethanol, and ultrasonically treating to obtain an organic phase; then adding the organic phase to a stabilizer solution and stirring until uniformly mixed to obtain the anti-inflammatory agent.

[0011] Furthermore, the mass ratio of dendrobine, resveratrol, and guaiacol is 2-5:1-3:5-8.

[0012] Furthermore, the concentration of the organic phase is 5-10 mg / mL.

[0013] Furthermore, the stirring speed is 300-500 rpm, and the stirring time is 5-8 min.

[0014] Furthermore, the stabilizer is povidone K30.

[0015] Furthermore, the volume ratio of the stabilizer solution to the organic phase is 20-35:1.

[0016] Furthermore, the concentration of the stabilizer solution is 0.4-0.7 mg / mL.

[0017] Furthermore, the preparation method of the repair agent includes: dissolving epidermal growth factor, sodium heparin, and mannitol in water, filtering, and obtaining the repair agent.

[0018] Furthermore, the mass-to-volume ratio of the epidermal growth factor, sodium heparin, mannitol, and water is 0.03-0.06:0.1-0.5:10-18:100-300.

[0019] Furthermore, the filtration refers to filtration using a 0.22 μm PES membrane.

[0020] Furthermore, the penetration enhancer includes any one of oleic acid, menthol, and propylene glycol; the regulator includes sodium chloride; the humectant includes any one of glycerin, polyethylene glycol, and propylene glycol; and the preservative includes any one of sodium benzoate, p-hydroxybenzoic acid, propylparaben, and benzalkonium chloride.

[0021] This invention also provides a method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury, comprising the following steps:

[0022] (1) Mix the penetration enhancer, regulator, humectant, preservative and water in proportion to obtain a mixed solution; add poloxamer 407 and poloxamer 188 to the mixed solution in proportion, and after full swelling, obtain a mixed adhesive solution;

[0023] (2) Disperse the functional ingredients evenly in the mixed gel solution described in step (1) and stir evenly to obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

[0024] Furthermore, the stirring speed in step (1) is in the range of 1500-3000 rpm.

[0025] Furthermore, in step (1), after adding poloxamer 407 and poloxamer 188, the stirring speed is in the range of 100-250 rpm.

[0026] Furthermore, the stirring speed in step (2) is in the range of 300-600 rpm.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The thermosensitive poloxamer gel for the prevention of vaginal radiation injury provided by this invention has a long residence time at the site of application, has a certain sustained-release effect, can maintain stimulation of the vaginal mucosa for a long time, helps the wound to heal quickly, can effectively prevent the occurrence of radiation vaginitis, and is convenient to use and safe and non-irritating to the human body. Detailed Implementation

[0029] This invention provides a thermosensitive poloxamer gel for the prevention of vaginal radiation injury, comprising the following components by weight percentage:

[0030] The composition consists of 6%-18% poloxamer complex, 3%-8% functional ingredients, 0.01%-0.08% penetration enhancer, 0.10%-0.45% regulator, 0.13%-0.25% humectant, 0.05%-0.12% preservative, and the balance being water.

[0031] The water used in this invention is preferably purified water.

[0032] In some embodiments of the present invention, the poloxamer complex is composed of poloxamer 407 and poloxamer 188.

[0033] In some embodiments of the present invention, the mass ratio of poloxamer 407 to poloxamer 188 in the poloxamer complex is 15-45:3-12.

[0034] In some embodiments of the present invention, the functional ingredients include an anti-inflammatory agent and a repairing agent, wherein the mass ratio of the anti-inflammatory agent to the repairing agent is 3-8:10-17.

[0035] In some embodiments of the present invention, the method for preparing the anti-inflammatory agent includes: mixing dendrobium, resveratrol, guaiacol and anhydrous ethanol, and ultrasonically treating to obtain an organic phase; then adding the organic phase to a stabilizer solution and stirring until uniformly mixed to obtain the anti-inflammatory agent.

[0036] In some embodiments of the present invention, the mass ratio of dendrobine, resveratrol, and guaiacol is 2-5:1-3:5-8.

[0037] In some embodiments of the present invention, the concentration of the organic phase is 5-10 mg / mL.

[0038] In some embodiments of the present invention, the stirring speed is 300-500 rpm and the stirring time is 5-8 min.

[0039] In some embodiments of the present invention, the stabilizer is povidone K30.

[0040] In some embodiments of the present invention, the volume ratio of the stabilizer solution to the organic phase is 20-35:1.

[0041] In some embodiments of the present invention, the concentration of the stabilizer solution is 0.4-0.7 mg / mL.

[0042] In some embodiments of the present invention, the method for preparing the repair agent includes: dissolving epidermal growth factor, sodium heparin, and mannitol in water, filtering, and obtaining the repair agent.

[0043] In some embodiments of the present invention, the mass-to-volume ratio of the epidermal growth factor, sodium heparin, mannitol and water is 0.03-0.06:0.1-0.5:10-18:100-300.

[0044] In some embodiments of the present invention, the filtration refers to filtration using a 0.22 μm PES membrane.

[0045] In some embodiments of the present invention, the penetration enhancer includes any one of oleic acid, menthol, and propylene glycol.

[0046] In some embodiments of the present invention, the regulator includes sodium chloride, and the humectant includes any one of glycerin, polyethylene glycol, and propylene glycol.

[0047] In some embodiments of the present invention, the preservative includes any one of sodium benzoate, p-hydroxybenzoic acid, propylparaben, and benzalkonium chloride.

[0048] This invention also provides a method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury, comprising the following steps:

[0049] (1) Mix the penetration enhancer, regulator, humectant, preservative and water in proportion to obtain a mixed solution; add poloxamer 407 and poloxamer 188 to the mixed solution in proportion, and after full swelling, obtain a mixed adhesive solution;

[0050] (2) Disperse the functional ingredients evenly in the mixed gel solution described in step (1) and stir evenly to obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

[0051] In some embodiments of the present invention, the stirring speed in step (1) is in the range of 1500-3000 rpm.

[0052] In some embodiments of the present invention, the stirring speed after adding poloxamer 407 and poloxamer 188 in step (1) is in the range of 100-250 rpm.

[0053] In some embodiments of the present invention, the stirring speed in step (2) is in the range of 300-600 rpm.

[0054] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0055] Unless otherwise specified, the test methods or experimental methods described in the following examples are all conventional methods; unless otherwise specified, the raw materials and additives are obtained from conventional commercial sources or prepared by conventional methods.

[0056] The preparation method of the anti-inflammatory agent described in Examples 1-3 below is as follows: Dendrobium phenol, resveratrol, guaiacol and anhydrous ethanol are mixed, the mass ratio of dendrobium phenol, resveratrol and guaiacol is 3:1:5, and ultrasonic treatment is performed at 300W for 15 min to obtain an organic phase solution with a concentration of 5 mg / mL; then, while stirring, the organic phase solution is added to a 0.7 mg / mL aqueous solution of povidone K30, the volume ratio of the aqueous solution of povidone K30 to the organic phase solution is 5:1, and the mixture is stirred at 500 rpm for 8 min to obtain the anti-inflammatory agent.

[0057] The preparation method of the repair agent described in Examples 1-3 below is as follows: epidermal growth factor, sodium heparin, and mannitol are dissolved in water, and the mass-volume ratio of epidermal growth factor, sodium heparin, mannitol and water is 0.06g:0.1g:12g:150mL. The solution is filtered through a 0.22μm PES membrane for sterilization to obtain the repair agent.

[0058] Dendrobium phenols, CAS No.: 83088-28-2, purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0059] Resveratrol, CAS No.: 501-36-0, was purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0060] Guaiacin, CAS No.: 90-05-1, purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0061] Povidone K30, also known as polyvinylpyrrolidone, CAS No. 9003-39-8, was purchased from Jinan Dahui Chemical Technology Co., Ltd.

[0062] Epidermal growth factor, also known as recombinant human epidermal growth factor, CAS No.: 62253-63-8, purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0063] Heparin sodium, CAS No.: 9041-08-1, purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0064] Mannitol, CAS No.: 87-78-5, purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0065] Poloxamer 407 and Poloxamer 188 were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0066] Example 1

[0067] A thermosensitive poloxamer gel for the prevention of vaginal radiation injury comprises, by weight percentage: 15% poloxamer complex, 7% functional ingredients, 0.03% oleic acid, 0.15% sodium chloride, 0.20% glycerin, 0.11% sodium benzoate, and the balance being water; wherein the poloxamer complex contains poloxamer 407 and poloxamer 188 in a weight ratio of 25:7, and the functional ingredients are composed of an anti-inflammatory agent and a repairing agent in a weight ratio of 5:11.

[0068] The specific steps for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury are as follows:

[0069] (1) Mix oleic acid, sodium chloride, glycerin, sodium benzoate and purified water in proportion and stir at 2000 rpm to obtain a mixed solution; after controlling the ambient temperature at 4℃, add poloxamer 407 and poloxamer 188 to the mixed solution in proportion and stir at 150 rpm until fully swollen to obtain a mixed gel.

[0070] (2) Maintain a temperature of 4°C, uniformly disperse the functional components in the mixed gel solution described in step (1), stir at 500 rpm until uniform, and adjust the pH of the system to 7.0 using a pH adjuster, namely triethanolamine, to obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

[0071] Example 2

[0072] A thermosensitive poloxamer gel for the prevention of vaginal radiation injury comprises, by weight percentage: 6% poloxamer complex, 3% functional ingredients, 0.01% menthol, 0.10% sodium chloride, 0.13% polyethylene glycol, 0.05% propylparaben, and the balance being water; wherein the poloxamer complex contains poloxamer 407 and poloxamer 188 in a weight ratio of 15:8, and the functional ingredients are composed of an anti-inflammatory agent and a repairing agent in a weight ratio of 5:11.

[0073] The specific steps for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury are as follows:

[0074] (1) Mix menthol, sodium chloride, polyethylene glycol, propylparaben and purified water in proportion and stir at 1500 rpm to obtain a mixed solution; after controlling the ambient temperature at 4℃, add poloxamer 407 and poloxamer 188 to the mixed solution in proportion and stir at 100 rpm until fully swollen to obtain a mixed gel.

[0075] (2) Maintain a temperature of 4°C, uniformly disperse the functional components in the mixed gel solution described in step (1), stir at 300 rpm until uniform, and adjust the pH of the system to 7.0 using a pH adjuster, namely triethanolamine, to obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

[0076] Example 3

[0077] A thermosensitive poloxamer gel for the prevention of vaginal radiation injury comprises, by weight percentage: 18% poloxamer complex, 8% functional ingredients, 0.08% propylene glycol, 0.45% sodium chloride, 0.25% glycerin, 0.12% benzalkonium chloride, and the balance being water; wherein the poloxamer complex contains poloxamer 407 and poloxamer 188 in a weight ratio of 45:11, and the functional ingredients are composed of an anti-inflammatory agent and a repairing agent in a weight ratio of 5:11.

[0078] The specific steps for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury are as follows:

[0079] (1) Mix propylene glycol, sodium chloride, glycerol, benzalkonium chloride and purified water in proportion and stir at 2000 rpm to obtain a mixed solution; after controlling the ambient temperature at 4℃, add poloxamer 407 and poloxamer 188 to the mixed solution in proportion and stir at 250 rpm until fully swollen to obtain a mixed gel solution.

[0080] (2) Maintain a temperature of 4°C, uniformly disperse the functional components in the mixed gel solution described in step (1), stir at 600 rpm until uniform, and adjust the pH of the system to 7.0 using a pH adjuster, namely triethanolamine, to obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

[0081] Comparative Example 1

[0082] The difference from Example 1 is that dendrobine was not added during the preparation of the anti-inflammatory agent, while the remaining steps are the same as in Example 1.

[0083] Comparative Example 2

[0084] The difference from Example 1 is that resveratrol was not added during the preparation of the anti-inflammatory agent, while the remaining steps were the same as in Example 1.

[0085] Comparative Example 3

[0086] The difference from Example 1 is that guaiacol was not added during the preparation of the anti-inflammatory agent, while the remaining steps are the same as in Example 1.

[0087] Comparative Example 4

[0088] The difference from Example 1 is that the mass ratio of dendrobine, resveratrol, and guaiacol is 1:3:5, while the remaining steps are the same as in Example 1.

[0089] Comparative Example 5

[0090] The difference from Example 1 is that the mass ratio of dendrobine, resveratrol, and guaiacol is 6:3:5, while the remaining steps are the same as in Example 1.

[0091] Comparative Example 6

[0092] The difference from Example 1 is that it does not contain epidermal growth factor, but the rest of the steps are the same as in Example 1.

[0093] Comparative Example 7

[0094] The difference from Example 1 is that it does not contain heparin sodium, but the rest of the steps are the same as in Example 1.

[0095] Performance testing

[0096] 1) Test the therapeutic effect of the examples and comparative examples on acute radiation vaginitis.

[0097] Case selection:

[0098] We selected 110 cervical cancer patients who received radical radiotherapy at the First Hospital of Jilin University between October 2021 and May 2022.

[0099] Inclusion criteria:

[0100] 1. Age between 18 and 65 years, in good physical condition, with an Eastern Cooperative Oncology Group Performance Status (ECOGPS) score of 0-2;

[0101] 2. Primary cervical cancer diagnosed by histopathology, FIGO stage IIa-IVa, with no contraindications to radiotherapy or chemotherapy;

[0102] 3. Before the test, hemoglobin, white blood cells, platelets, alanine aminotransferase, neutrophil count, creatinine, urea, etc. were all normal.

[0103] Exclusion criteria:

[0104] 1. Pre-existing gynecological inflammation;

[0105] 2. Did not receive radical radiotherapy;

[0106] 3. Has received pelvic and abdominal radiation therapy;

[0107] 4. Individuals with distant metastases (stage IVB) at the time of diagnosis;

[0108] 5. Congenital vaginal stenosis;

[0109] 6. Individuals who were already enrolled in another clinical study at the time of inclusion in the study.

[0110] This study was approved by the hospital's ethics committee. All cervical cancer patients were fully informed of the benefits and risks of participating in this study and agreed to sign the informed consent form.

[0111] Test method:

[0112] One hundred and ten cervical cancer patients were randomly divided into 11 groups: a control group, Example 1, Example 2, Example 3, and Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5, Comparative Example 6, and Comparative Example 7. All 11 groups received pelvic external beam radiation therapy and intracavitary brachytherapy. External beam radiation therapy consisted of 46-60 Gy / 23-30 fractions, 5 times per week. Intracavitary brachytherapy consisted of 28 Gy / 4 fractions, 2 times per week.

[0113] Control group: Before daily radiotherapy, the experimental patients were irrigated with a vaginal douche. The procedure was as follows: 500ml of 0.05% povidone-iodine solution was poured into a vaginal douche device and the vagina was irrigated 1-2 times by professional staff from the hospital.

[0114] Experimental groups (Example 1, Example 2, Example 3 and Comparative Examples 1, 2, 3, 4, 5, 6 and 7 are collectively referred to as experimental groups): Based on the control group (after vaginal irrigation), the syringe filled with gel material from the examples or comparative examples was gently inserted into the vagina to a depth of 6-8 cm. Then, the gel material in the syringe was slowly pushed into the vagina to evenly cover the anterior, posterior and lateral walls of the vagina. After administration, the patient should lie flat for 15-30 minutes before moving.

[0115] Treatment frequency: 2g once every 2 days, 5 times for 1 course of treatment, for a total of 30 days, then change to 2 times / week until the end of radiotherapy.

[0116] Evaluation criteria:

[0117] The degree of vaginal radiation injury is assessed according to the Radiation Therapy Oncology Group (RTOG) grading system for acute radiation reactions. Radiation vaginitis is classified into 5 grades:

[0118] Grade 0, no changes in vaginal mucosa;

[0119] Grade I: Vaginal mucosal congestion, edema, and mild pain;

[0120] Grade II: Vaginal mucosal congestion, edema, and punctate ulcers;

[0121] Grade III: Vaginal mucosal congestion, edema, patchy ulcers covered with a white membrane, and increased pain;

[0122] Grade IV, extensive vaginal mucosal ulceration and severe pain, requiring discontinuation of radiotherapy.

[0123] The onset time of acute radiation-induced vaginal injury is calculated from the start of radiotherapy.

[0124] The experimental results are shown in the table below.

[0125]

[0126] As shown in the table above, the thermosensitive poloxamer gel prepared in this embodiment of the invention can effectively prevent vaginal radiation damage, reduce the incidence of acute radiation vaginitis, and also reduce the occurrence of severe radiation vaginitis. Comparative Examples 1-3 all used single active ingredients, and their preventive effects on radiation vaginitis were poor, indicating that the combined use of dendrobium, resveratrol, and guaiacol is more effective in preventing radiation vaginitis than a single ingredient. The repair agents described in Comparative Examples 6-7, which do not contain epidermal growth factor or heparin sodium, also showed poor preventive effects on radiation vaginitis, indicating that there is a synergistic effect between epidermal growth factor and heparin sodium in preventing radiation vaginitis.

[0127] Comparative Examples 4-5 present technical solutions with mass ratios of dendrobium, resveratrol, and guaiacol higher or lower than those of this invention. The results show that when the mass ratio of dendrobium, resveratrol, and guaiacol is outside the scope of this invention, the prepared gel cannot effectively prevent radiation vaginitis. This indicates that although there is a synergistic effect between dendrobium, resveratrol, and guaiacol, the preventive effect against radiation vaginitis is better only within a specific ratio range.

[0128] (ii) The vaginal mucosal irritation test was performed on the gel material prepared in Example 1. The test procedure is as follows:

[0129] The vaginal mucosal irritation test was conducted according to Section 2.3.5 of Part II, "Technical Specifications for Inspection of Disinfection Products," of the 2002 edition of the "Disinfection Technical Specifications" issued by the Ministry of Health. The test temperature was 22℃-25℃, and the RH was 60%-65%.

[0130] 1) Prepare experimental animals and syringes filled with the test gel: Randomly divide healthy female white rabbits into a treatment group and a control group, with 3 rabbits in each group. Connect an 8 cm blunt-tipped soft tube to a 2 mL syringe and fill it with the test solution. Prepare one set for each experimental animal.

[0131] 2) Experimental procedure: Fix the animal supine, exposing the perineum and vaginal opening; after moistening the catheter with the test gel, gently insert it into the vagina of the test animal (4-5 cm), and slowly inject 2 mL of the test gel provided in Example 1. After the procedure, remove the catheter to complete the drug treatment.

[0132] The control group animals were treated with physiological saline in the same way.

[0133] Twenty-four hours after exposure, the animals were euthanized using an air embolization method. The intact vagina was removed via laparotomy and longitudinally incised for visual inspection to check for congestion, edema, or other signs of infection. The vagina was then fixed in 10% formalin solution for 24 hours. Tissue sections were prepared from three locations: both ends and the center of the vagina. After HE staining, histopathological examination was performed, and the irritation reaction was scored according to the vaginal mucosal irritation reaction scoring criteria in section 2.3.5 of the "Disinfection Technical Specifications" (2002 edition).

[0134] 3) Experimental results: No abnormalities were found in the longitudinal section of the vagina by visual observation, and the stimulation index was 0.9 (<1).

[0135] This indicates that the gel material prepared in Example 1 of the present invention does not irritate the vaginal mucosa of white rabbits and has good safety.

[0136] Meanwhile, the present invention also conducted vaginal mucosal irritation tests on the temperature-sensitive poloxamer gels prepared in Examples 2-3, and the results were comparable to those in Example 1, showing no irritation to the vaginal mucosa of white rabbits and good safety.

[0137] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A thermosensitive poloxamer gel for the prevention of vaginal radiation injury, characterized in that, By weight percentage, it includes the following components: The composition consists of 6%-18% poloxamer complex, 3%-8% functional ingredients, 0.01%-0.08% penetration enhancer, 0.10%-0.45% regulator, 0.13%-0.25% humectant, 0.05%-0.12% preservative, and the balance being water. The poloxamer complex is composed of poloxamer 407 and poloxamer 188.

2. The thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 1, characterized in that, The mass ratio of poloxamer 407 to poloxamer 188 in the poloxamer complex is 15-45:3-12.

3. The thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 1, characterized in that, The functional ingredients include anti-inflammatory agents and repair agents.

4. The thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 1, characterized in that, The method for preparing the anti-inflammatory agent includes: mixing dendrobine, resveratrol, guaiacol and anhydrous ethanol, and ultrasonically treating to obtain an organic phase; then adding the organic phase to a stabilizer solution and stirring until uniformly mixed to obtain the anti-inflammatory agent.

5. The thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 1, characterized in that, The preparation method of the repair agent includes: dissolving epidermal growth factor, sodium heparin, and mannitol in water, filtering, and obtaining the repair agent.

6. The thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 1, characterized in that, The penetration enhancer includes any one of oleic acid, menthol, and propylene glycol; the regulator includes sodium chloride; the humectant includes any one of glycerin, polyethylene glycol, and propylene glycol; and the preservative includes any one of sodium benzoate, p-hydroxybenzoic acid, propylparaben, and benzalkonium chloride.

7. The method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to any one of claims 1-6, characterized in that, Includes the following steps: (1) Mix the penetration enhancer, regulator, humectant, preservative and water in proportion to obtain a mixed solution; add poloxamer 407 and poloxamer 188 to the mixed solution in proportion, and after full swelling, obtain a mixed adhesive solution; (2) Disperse the functional ingredients evenly in the mixed gel solution described in step (1), stir evenly, and obtain a thermosensitive poloxamer gel for the prevention of vaginal radiation injury.

8. The method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 7, characterized in that, The stirring speed in step (1) is in the range of 1500-3000 rpm.

9. The method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 7, characterized in that, After adding poloxamer 407 and poloxamer 188 in step (1), the stirring speed is in the range of 100-250 rpm.

10. The method for preparing the thermosensitive poloxamer gel for the prevention of vaginal radiation injury according to claim 7, characterized in that, The stirring speed in step (2) is in the range of 300-600 rpm.

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