Gynecological vagina mucosa repairing gel and preparation method thereof

Abstract

The invention relates to the technical field of medical gel, in particular to gynecological vaginal mucosa repairing gel and a preparation method thereof. Comprising the following raw materials: carbomer, glycerol, sodium hyaluronate, vitamin E, potassium sorbate, a modified nano polylactic acid-glycolic acid copolymer, modified nano collagen, albumin, tea tree essential oil, aloe, astragalus membranaceus, dandelion, stigma croci and ginseng. The modified nano polylactic acid-glycolic acid copolymer, the modified nano collagen and the albumin play a role through a synergistic effect, and the modified nano polylactic acid-glycolic acid is used as a skeleton structure for cell growth and is firmly attached to the active pharmaceutical ingredient-albumin compound; the polyacrylic acid chain on the surface controls the drug release rate by sensing the change of the pH value, the albumin initiates endocytosis through specific binding, and the albumin and the modified nano collagen jointly improve the anti-inflammatory performance, promote cell proliferation and differentiation and promote repair and regeneration of vaginal mucosa tissues.

Description

Technical Field

[0001] The invention relates to the technical field of medical gels, in particular to a gynecological vaginal mucosa repairing gel and a preparation method thereof. Background Art

[0002] In the field of women's health, vaginal mucosal injury is a common disease, and there are many reasons for its occurrence, including physiological factors, infection factors, improper behavior and iatrogenic factors. For example, during menstruation, the vaginal mucosa is easily damaged by hormones, bacterial, fungal or trichomoniasis and other infections can cause mucosal inflammation and injury, and improper behaviors such as frequent use of vaginal douches or tampons can cause mucosal damage. Due to these reasons, vaginal mucosal injury has a high incidence rate in women. For this disease, local drug therapy is an important treatment method, which can directly act on the damaged mucosa, increase drug concentration, and avoid the side effects of oral drug therapy and systemic treatment. As a topically applied drug product, gynecological vaginal mucosal repair gel has many advantages. It can directly act on the damaged mucosa and is easy to use. It has good bioadhesion and can stay on the mucosal surface for a long time, which is conducive to the sustained release and absorption of drugs and improves drug utilization. It also has excellent biocompatibility and can effectively reduce irritation to the mucosa. It has been widely used in clinical practice. Therefore, it is of great significance to develop a safe and effective gynecological vaginal mucosal repair gel. However, the current gynecological vaginal mucosa repair gel still has some shortcomings and deficiencies in cell tissue repair and regeneration, which needs further improvement. Therefore, it is considered to enhance the cell tissue repair and regeneration function of the gynecological vaginal mucosa repair gel, and at the same time adjust the drug release rate according to the pH changes of the physiological environment, thereby improving the bioavailability of the drug, accelerating the cell tissue repair and regeneration process, creating an immune microenvironment that is conducive to tissue repair, and allowing patients to recover sooner.

[0003] (1) Technical issues to be solved

[0004] The purpose of the present invention is to provide a gynecological vaginal mucosa repair gel and a preparation method thereof, so as to enhance the cell tissue repair and regeneration function of the gynecological vaginal mucosa repair gel, and at the same time adjust the drug release rate according to the pH value change of the physiological environment, improve the bioavailability of the drug, accelerate the cell tissue repair and regeneration process, create an immune microenvironment conducive to tissue repair, and enable the patient to recover as soon as possible.

[0005] (2) Technical solution

[0006] To achieve the above object, on the one hand, the present invention provides a gynecological vaginal mucosa repair gel, comprising the following raw materials in parts by weight: 6-12 parts of carbomer, 2-5 parts of glycerin, 1-2 parts of sodium hyaluronate, 1-2 parts of vitamin E, 0.5-1 part of potassium sorbate, 0.2-1 part of modified nano-collagen, 0.2-1 part of albumin, 0.5-1 part of tea tree essential oil, 2-4 parts of aloe, 1-2 parts of astragalus, 2-3 parts of dandelion, 1-2 parts of saffron, and 1-2 parts of ginseng;

[0007] Modified nano polylactic acid-glycolic acid copolymer;

[0008] The modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1: (6-12);

[0009] The modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it;

[0010] The modified nano polylactic acid-glycolic acid copolymer has a particle size of 80 to 100 nm and a specific surface area of ​​50 to 80 m 2 / g.

[0011] Furthermore, the preparation method of the modified nano polylactic acid-glycolic acid copolymer comprises:

[0012] S11. Slowly adding the polylactic acid-glycolic acid copolymer to anhydrous dichloromethane under stirring, stirring for 0.5 to 1 h, and then filtering with a 0.22 μm filter membrane to obtain a polylactic acid-glycolic acid copolymer solution;

[0013] S12. dissolving polyacrylic acid in purified water under stirring, stirring for 0.5 to 1 h, and then adjusting the pH value to 4.5 to 5.0 with 0.1 mol / L dilute hydrochloric acid solution to obtain a polyacrylic acid solution;

[0014] S13. slowly dropwise adding the polylactic acid-co-glycolic acid solution into the polyvinyl alcohol aqueous solution for ultrasonic treatment and setting the pulse mode to an ultrasonic frequency of 40 to 50 kHz, and then slowly adding the polyacrylic acid solution after ultrasonic treatment at room temperature for 15 to 30 minutes, and continuing the ultrasonic treatment for 10 to 20 minutes to obtain a first mixed solution;

[0015] S14. The first mixed solution was transferred to a magnetic stirrer at a speed of 500 to 800 rpm and stirred at room temperature for 6 to 8 hours to obtain a second mixed solution;

[0016] S15. The second mixed solution was subjected to high-speed centrifugation at a speed of 12000 to 15000 rpm for 15 to 20 min, and the separated solid was washed three times with phosphate buffered saline and then freeze-dried;

[0017] S16. After the solid is precooled at -60 to -80°C for 2 to 4 hours, the freeze-drying temperature is set to -40 to -50°C, and after drying for 24 to 30 hours, the modified nano polylactic acid-glycolic acid copolymer is obtained and ground into powder for later use.

[0018] Furthermore, the mass ratio of the polylactic acid-glycolic acid copolymer to polyacrylic acid is 1:(0.1-0.2).

[0019] Furthermore, the preparation method of the modified nano-collagen comprises:

[0020] S21. Dissolve collagen in acetic acid, stir at room temperature for 0.5 to 1 h, transfer to a high-pressure homogenizer, set the pressure to 800 to 1000 bar, and cycle 10 to 15 times to obtain a nano-collagen solution;

[0021] S22. The pH value of the nano-collagen solution is adjusted to 8.5-9.0 with 0.1 mol / L sodium hydroxide solution, and chlorosulfonic acid is slowly added at 0-4°C, and the reaction is continued with stirring for 4-6 hours, and then the pH value is adjusted to 7.0-7.5 to obtain a third mixed solution;

[0022] S23. The third mixed solution is transferred to a dialysis bag and dialyzed in a phosphate buffered saline for 36 to 48 hours, with the phosphate buffered saline being replaced every 12 hours. After the dialysis is completed, a fourth mixed solution is obtained;

[0023] S24. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are slowly added dropwise to the fourth mixed solution for ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. After ultrasonic treatment for 0.5 to 1 h at room temperature, growth factors are added, and the reaction is continued with stirring at 0 to 4° C. for 24 to 30 h to obtain a fifth mixed solution;

[0024] S25. The fifth mixed solution is transferred to a dialysis bag, and dialyzed in a phosphate buffered saline at 0 to 4°C for 48 to 52 hours, with the phosphate buffered saline being replaced every 12 hours, to obtain a modified nano-collagen solution after the dialysis is completed;

[0025] S26. Freeze-dry the modified nano-collagen solution at a drying temperature of -40 to -60°C. After drying for 12 to 18 hours, the modified nano-collagen is obtained and ground into powder for later use.

[0026] Furthermore, the modified nano-collagen is coupled with growth factors and contains sulfate groups on the surface, with a particle size of 45 to 65 nm and a specific surface area of ​​120 to 180 m 2 / g.

[0027] Furthermore, the mass ratio of the collagen, chlorosulfonic acid and growth factor is 1:(0.05-0.1):(0.02-0.05).

[0028] On the other hand, based on the same inventive concept, the present invention also provides a method for preparing a gynecological vaginal mucosa repair gel, which is applied to the gynecological vaginal mucosa repair gel, comprising the following steps:

[0029] S31. Add purified water to the container, add carbomer to the container, stir evenly, then add glycerin, sodium hyaluronate, vitamin E and potassium sorbate in sequence and stir, while heating in a water bath at a temperature of 70 to 80 ° C until fully dissolved to obtain a sixth mixed solution;

[0030] S32. Wash and dry aloe, astragalus, dandelion, saffron and ginseng, crush and add purified water and 60-80% ethanol, place in an ultrasonic extractor, extract at 55-65°C, extract for 2-4h to obtain a first extract;

[0031] S33. Purified water and 60-80% ethanol were added again to continue extraction, twice in a row, to obtain a second extract and a third extract, respectively, and the extracts were mixed and concentrated under reduced pressure to obtain a composite extract of Chinese herbal medicine;

[0032] S34. The tea tree essential oil, albumin, modified nano collagen and Chinese herbal compound extract are sequentially added to the sixth mixed solution under stirring, and the modified nano polylactic acid-glycolic acid copolymer is added after stirring for 0.5 to 1 h, and the stirring is continued for 2 to 4 h to obtain a sixth mixed solution;

[0033] S35. Transfer the sixth mixed solution to a high-pressure homogenizer, set the pressure to 800-1000 bar, and filter through a 0.22 μm filter membrane after circulating 5-10 times. Put the filtered gynecological vaginal mucosa repair gel into a sterile container, and store it in a sealed and cool dry place.

[0034] Furthermore, the temperature of the reduced pressure concentration is 55-65° C. and the pressure is 0.5-0.8 bar.

[0035] Furthermore, the method of using the gynecological vaginal mucosa repair gel is as follows: wash your hands, gently insert the gel device into the vagina, push the gel device, slowly squeeze the gel into the patient's vagina, lie on your back for 6 to 8 minutes, and a course of treatment is 7 to 9 days, depending on the degree of recovery of the injury.

[0036] The mechanism of action of the above raw material components is as follows:

[0037] Carbomer is a high molecular polymer that has the functions of thickening, suspending and stabilizing agent, and is often used as a pharmaceutical thickener and emulsifier. Glycerol is a simple polyol compound. Because it has three hydroxyl groups (-OH), it is miscible with water and has hygroscopicity, and has good permeability. In the repair gel, glycerol can relieve vaginal dryness, relieve itching and discomfort, and also help protect the skin. Sodium hyaluronate is a linear polysaccharide formed by alternating D-glucuronic acid and N-acetyl-D-glucosamine. It contains a large number of hydroxyl groups (-OH) and carboxyl groups (-COOH), has good biocompatibility, and is a strong moisturizing ingredient that helps repair and moisturize the vaginal mucosa. Vitamin E is an antioxidant that can protect cells from oxidative stress damage, reduce inflammatory reactions, relieve tissue irritation, and accelerate the repair process of skin and mucosa. Potassium sorbate is a commonly used preservative that can inhibit microbial growth and improve product stability, so that the product maintains high activity in a wide pH range and extends the shelf life of the product.

[0038] The main chemical components of tea tree essential oil are terpenes, which can destroy the cell membrane structure of microorganisms, interfere with the energy metabolism process of microorganisms, and have a significant inhibitory effect on bacteria, fungi and certain viruses. At the same time, they can reduce local inflammatory reactions, relieve discomfort symptoms, and accelerate the repair process of skin and mucous membranes. Aloe vera mainly includes a variety of active ingredients such as polysaccharides, anthraquinones, amino acids, vitamins and minerals. It has a moisturizing effect, can relieve skin and reduce mucous membrane irritation, and at the same time promote wound healing, reduce scar formation, and enhance local immunity. Astragalus is a common Chinese herbal medicine with antioxidant and anti-inflammatory effects. Its main ingredients include astragalic acid, astragalone, astragalin, etc., which have anti-inflammatory and antioxidant effects, can effectively relieve vaginal inflammation and other inflammatory reactions, improve vaginal immunity, and promote tissue repair. The main active ingredients of dandelion are dandelion alcohol, chlorogenic acid and flavonoids, which can promote the discharge of toxins and metabolites in the body, inhibit the production of inflammatory mediators, relieve local inflammatory states, and improve the body's resistance. The main active ingredients of saffron include crocinaldehyde, crocin and kaempferol, which can improve blood circulation, promote tissue repair and regeneration, reduce local inflammatory reactions, regulate serotonin and dopamine concentrations, regulate emotions, and improve psychological state. The main active ingredients of ginseng include ginsenosides, ginseng polysaccharides and ginsenoside alcohol, which can regulate immune function, enhance T cell and NK cell activity, improve body resistance, enhance mitochondrial function, promote energy metabolism, and accelerate cell tissue repair and regeneration.

[0039] Albumin is the most abundant protein in human plasma and is mainly synthesized by the liver. In gynecological vaginal mucosal repair gel, it has multiple effects such as enhancing mucosal moisturizing effect, enhancing biocompatibility, promoting wound healing, and enhancing gel stability. Collagen is the most abundant protein in the human body and the main component of connective tissue. It has excellent biocompatibility and low immunogenicity. Collagen is nano-sized and chemically modified to introduce sulfate groups and coupled growth factors on its surface to obtain modified nano-collagen. Modified nano-collagen has unique advantages in promoting epithelial cell regeneration, regulating vaginal microenvironment, and regulating immune response. Polylactic acid-glycolic acid copolymer is a biodegradable polymer material formed by the esterification reaction of two monomers, lactic acid and glycolic acid. Due to its good biocompatibility and controllable degradability, it is used as a drug delivery system, tissue engineering scaffolds and other biomedical applications. The modified nano polylactic acid-glycolic acid copolymer is obtained by nano-sizing the polylactic acid-glycolic acid copolymer and grafting a pH-sensitive polyacrylic acid polymer on its surface, which further enhances the functionality of the modified nano polylactic acid-glycolic acid copolymer and enables the modified nano polylactic acid-glycolic acid copolymer to adjust the drug release rate according to changes in the pH value of the vaginal physiological environment.

[0040] In the gynecological vaginal mucosa repair gel, modified nano polylactic acid-glycolic acid copolymer, modified nano collagen and albumin play a role through synergistic effects. When preparing the gynecological vaginal mucosa repair gel, albumin forms a stable active drug ingredient-albumin complex with modified nano collagen, Chinese herbal medicine compound extract and other active drug ingredients through its hydrophilicity and hydrophobicity. The modified nano polylactic acid-glycolic acid copolymer prepared by the emulsification-solvent evaporation method can be used as a drug sustained-release carrier due to its high specific surface area and rich pore structure, and interacts with these active drug ingredients-albumin complexes through physical adsorption and chemical action to make them firmly attached to the porous structure of the modified nano polylactic acid-glycolic acid copolymer, while also providing a stable microenvironment for the active drug ingredients. Under normal physiological conditions, the pH value of the vaginal environment is between 3.8 and 4.5. However, when there is inflammation or vaginal mucosal tissue damage, the pH value of the vaginal environment will increase. When the gynecological vaginal mucosal repair gel acts on the damaged vaginal tissue mucosa, the modified nano polylactic acid-glycolic acid copolymer senses the pH change, and the polyacrylic acid side chains on its surface are protonated to cause the modified nano polylactic acid-glycolic acid copolymer particles to swell, thereby accelerating drug release and releasing more active drug ingredients-albumin complexes in a timely manner. At the same time, albumin specifically binds to the albumin receptors on the surface of the vaginal epithelial cells at the injured site, triggering receptor-mediated endocytosis, so that the active drug ingredient-albumin complex is directly engulfed by the cells to form vesicles. Under the action of lysosomes, the active drug ingredient-albumin complex is decomposed, releasing drug ingredients such as modified nano-collagen and active components of traditional Chinese medicine. The sulfate groups on the surface of modified nano-collagen can better bind and stabilize growth factors by simulating sulfated glycosaminoglycans in the extracellular matrix, while also enhancing the interaction with damaged cells, and together with albumin, improve the body's anti-inflammatory properties. Growth factors directly promote cell proliferation and differentiation, thereby accelerating the repair and regeneration of cell tissues. In addition, the presence of albumin further avoids the agglomeration effect that occurs when modified nano-polylactic acid-glycolic acid copolymer and modified nano-collagen exist at the same time, thereby protecting the structural integrity of modified nano-polylactic acid-glycolic acid copolymer and modified nano-collagen. With the natural metabolism of the human body, the modified nano polylactic acid-glycolic acid copolymer is gradually decomposed into lactic acid and glycolic acid and absorbed and utilized by the human body. The released lactic acid further promotes the synthesis of collagen in the injured tissue. At the same time, the modified nano polylactic acid-glycolic acid copolymer particles themselves can serve as a skeleton structure for cell growth, creating a good immune microenvironment for the repair of tissue cells, and together with drug ingredients such as albumin, modified nano collagen and active components of traditional Chinese medicine, promote the repair and regeneration of vaginal mucosal tissue.

[0041] (3) Beneficial effects

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] 1. The modified nano-polylactic acid-glycolic acid copolymer, modified nano-collagen and albumin play a role through synergistic effect. Albumin forms a stable active pharmaceutical ingredient-albumin complex with modified nano-collagen, Chinese herbal medicine compound extract and other active pharmaceutical ingredients through its hydrophilicity and hydrophobicity, and is firmly attached to the modified nano-polylactic acid-glycolic acid copolymer under the physical adsorption and chemical action;

[0044] 2. The polyacrylic acid side chains on the surface of the modified nano-polylactic acid-glycolic acid copolymer control the drug release rate by sensing the changes in the pH value of the vaginal environment. When the pH value of the vaginal environment increases due to inflammation or damage to the vaginal mucosal tissue, the release of the drug active ingredient-albumin complex is accelerated;

[0045] 3. Albumin specifically binds to the albumin receptors on the surface of vaginal epithelial cells to trigger endocytosis, so that the active ingredient-albumin complex is directly engulfed by the cells to form vesicles, and the modified nano-collagen and active components of traditional Chinese medicine are released under the action of lysosomes;

[0046] 4. The sulfate groups on the surface of modified nano-collagen can better bind and stabilize growth factors by simulating sulfated glycosaminoglycans in the extracellular matrix, enhance the interaction with damaged cells, and improve the body's anti-inflammatory properties together with albumin. Growth factors directly promote cell proliferation and differentiation, and accelerate the repair and regeneration of cell tissues.

[0047] 5. The lactic acid released by the gradual decomposition of the modified nano-polylactic acid-glycolic acid copolymer further promotes the synthesis of collagen in the injured tissue, and as a skeleton structure for cell growth, it creates a good immune microenvironment for the repair of tissue cells, and together with drug ingredients such as albumin, modified nano-collagen and active components of traditional Chinese medicine, promotes the repair and regeneration of vaginal mucosal tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 This is a SEM image of the modified nano polylactic acid-glycolic acid copolymer of Example 1 of the present invention;

[0049] Figure 2 This is the SEM image of the modified nano-collagen in Example 1 of the present invention;

[0050] Figure 3 These are SEM images of the vaginal tissue of the vaginal tissue injury model rats in Example 1 of the present invention before (a) and after (b) using the gynecological vaginal mucosa repair gel. DETAILED DESCRIPTION

[0051] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0052] The experimental equipment and preparations of the embodiments described below are as follows: electronic balance (Sartorius, Germany), electric constant temperature water bath (Jiangsu Kedao), magnetic stirrer (Shanghai Meiyingpu), ultrasonic instrument (Shanghai Yixin), high-speed centrifuge (Guangzhou Jidi), ultrasonic extractor (Guangdong Jiemeng), dialyzer (Jinan Zhuyan), vacuum homogenizer (Shanghai Noze), rotary evaporator (Shanghai Yaote), scanning electron microscope (Germany Zeiss), specific surface area analyzer (Beijing Best Instrument Technology), freeze dryer (Shanghai Pudong Freeze Drying), pH meter (Shanghai Yidian), variable magnification stereo microscope (Olympus, Japan); Chinese medicinal materials were purchased from Tong Ren Tang Pharmacy, and chemical drugs and reagents were purchased from Sigma-Aldrich.

[0053] Embodiment 1: This embodiment discloses a gynecological vaginal mucosa repair gel, comprising 9 parts of carbomer, 3 parts of glycerol, 1.5 parts of sodium hyaluronate, 1.5 parts of vitamin E, 0.8 parts of potassium sorbate, 0.6 parts of modified nano collagen, 0.6 parts of albumin, 0.8 parts of tea tree essential oil, 3 parts of aloe vera, 1.5 parts of astragalus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel also comprises a modified nano polylactic acid-glycolic acid copolymer, wherein the modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1:9, wherein the modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing the modified nano polylactic acid-glycolic acid copolymer, wherein the particle size of the modified nano polylactic acid-glycolic acid copolymer is 80-100 nm, and the specific surface area is 50-80 m 2 / g.

[0054] In the gynecological vaginal mucosa repair gel, modified nano polylactic acid-glycolic acid copolymer, modified nano collagen and albumin play a role through synergistic effect. When preparing the gynecological vaginal mucosa repair gel, albumin is a multifunctional protein with a flexible structure. There are multiple hydrophobic binding sites such as Sudlow on its surface. At the same time, it is rich in charged amino acid residues and shows hydrophilicity. Modified nano collagen, Chinese herbal compound extracts and other active pharmaceutical ingredients form stable active pharmaceutical ingredient-albumin complexes with albumin through the hydrophilicity and hydrophobicity of albumin. Figure 1As shown in the figure, the modified nano polylactic acid-glycolic acid copolymer prepared by the emulsification-solvent evaporation method has a rich porous structure and a large specific surface area, which can be used as a drug sustained-release carrier. Its high specific surface area and large porosity provide a large number of adsorption sites for the active drug ingredient-albumin complex. At the same time, through electrostatic interaction and covalent action, these active drug ingredients-albumin complexes are firmly attached to the porous structure of the modified nano polylactic acid-glycolic acid copolymer, and at the same time, a stable microenvironment is provided for the active drug ingredients, protecting the drugs from the influence of the external environment and maintaining the activity of the drugs. Under normal physiological conditions, the pH value of the vaginal environment is between 3.8 and 4.5, but the pH value of the vaginal environment will increase when there is inflammation, vaginal mucosal tissue damage, etc. When the gynecological vaginal mucosal repair gel acts on the damaged vaginal tissue mucosa, the modified nano polylactic acid-glycolic acid copolymer senses the pH change, and the carboxyl group (-COOH) of the polyacrylic acid side chain on its surface will be protonated to remove one H + The negatively charged carboxyl anion (-COO - ), negatively charged carboxyl anion (-COO - ) generate electrostatic repulsion between each other, which makes the carbon chain of the modified nano polylactic acid-glycolic acid copolymer stretch, causing the nanoparticles to expand, while weakening the electrostatic attraction with the positively charged albumin and the active pharmaceutical ingredient, so that the active pharmaceutical ingredient-albumin complex is dissociated from the porous structure of the modified nano polylactic acid-glycolic acid copolymer, releasing the active pharmaceutical ingredient-albumin complex, and at the same time, albumin specifically binds to the albumin receptors on the surface of the vaginal epithelial cells at the injured site to trigger receptor-mediated endocytosis, so that the active pharmaceutical ingredient-albumin complex is directly swallowed by the cells to form vesicles, and the active pharmaceutical ingredient-albumin complex is decomposed under the action of lysosomes, releasing pharmaceutical ingredients such as the modified nano collagen and the active pharmaceutical ingredient of traditional Chinese medicine. Figure 2This is the SEM image of modified nano-collagen. It can be seen that the modified nano-collagen has uniform particle size, spherical morphology and a certain fiber structure. The sulfate group (-SO3H) on the surface of the modified nano-collagen increases the negative charge density of the modified nano-collagen. By simulating the sulfated glycosaminoglycans in the extracellular matrix, the growth factors can be better combined and stabilized during the preparation of the modified nano-collagen. At the same time, it also enhances the interaction with damaged cells, and together with albumin, it improves the body's anti-inflammatory properties and creates favorable conditions for tissue repair. The growth factors coupled to the surface of the modified nano-collagen directly promote cell proliferation and differentiation, thereby accelerating the repair and regeneration of cell tissues. In addition, the presence of albumin further avoids the occurrence of the co-existence of modified nano-polylactic acid-glycolic acid copolymer and modified nano-collagen. Agglomeration will cause the bioactive sites of modified nano-collagen and modified nano-polylactic acid-glycolic acid copolymer to be shielded, and the large particles formed by agglomeration will affect the uniformity of distribution of drug active ingredients on the vaginal mucosa. At the same time, nanoparticles that are too large are difficult to be taken up by cells, thereby reducing their ability to promote cell attachment and growth. However, albumin protects the structural integrity of modified nano-polylactic acid-glycolic acid copolymer and modified nano-collagen. Albumin molecules are adsorbed on the surface of modified nano-collagen to form a protective film. The hydrophilic amino acid residues such as serine (-CH2OH), threonine (-CH(OH)CH3) and asparagine (-CH2CONH2) on its surface form hydrogen bonds with water molecules to create a hydration layer, which prevents the modified nano-polylactic acid-glycolic acid copolymer from approaching through a steric repulsion effect. With the natural metabolism of the human body, the modified nano polylactic acid-glycolic acid copolymer is gradually decomposed into lactic acid and glycolic acid and absorbed and utilized by the human body. The released lactic acid further promotes the synthesis of collagen in the injured tissue. At the same time, the modified nano polylactic acid-glycolic acid copolymer particles themselves can serve as a skeleton structure for cell growth, creating a good immune microenvironment for the repair of tissue cells, and together with drug ingredients such as albumin, modified nano collagen and active components of traditional Chinese medicine, promote the repair and regeneration of vaginal mucosal tissue.

[0055] The preparation method of the modified nano polylactic acid-glycolic acid copolymer comprises:

[0056] S11. Slowly adding the polylactic acid-glycolic acid copolymer to anhydrous dichloromethane under stirring, stirring for 0.5 to 1 h, and then filtering with a 0.22 μm filter membrane to obtain a polylactic acid-glycolic acid copolymer solution;

[0057] S12. dissolving polyacrylic acid in purified water under stirring, stirring for 0.5 to 1 h, and then adjusting the pH value to 4.5 to 5.0 with 0.1 mol / L dilute hydrochloric acid solution to obtain a polyacrylic acid solution;

[0058] S13. slowly dropwise adding the polylactic acid-co-glycolic acid solution into the polyvinyl alcohol aqueous solution for ultrasonic treatment and setting the pulse mode to an ultrasonic frequency of 40 to 50 kHz, and then slowly adding the polyacrylic acid solution after ultrasonic treatment at room temperature for 15 to 30 minutes, and continuing the ultrasonic treatment for 10 to 20 minutes to obtain a first mixed solution;

[0059] S14. The first mixed solution was transferred to a magnetic stirrer at a speed of 500 to 800 rpm and stirred at room temperature for 6 to 8 hours to obtain a second mixed solution;

[0060] S15. The second mixed solution was subjected to high-speed centrifugation at a speed of 12000 to 15000 rpm for 15 to 20 min, and the separated solid was washed three times with phosphate buffered saline and then freeze-dried;

[0061] S16. After the solid is precooled at -60 to -80°C for 2 to 4 hours, the freeze-drying temperature is set to -40 to -50°C, and after drying for 24 to 30 hours, the modified nano polylactic acid-glycolic acid copolymer is obtained and ground into powder for later use.

[0062] The mass ratio of the polylactic acid-glycolic acid copolymer to polyacrylic acid is 1:(0.1-0.2).

[0063] The preparation method of the modified nano collagen comprises:

[0064] S21. Dissolve collagen in acetic acid, stir at room temperature for 0.5 to 1 h, transfer to a high-pressure homogenizer, set the pressure to 800 to 1000 bar, and cycle 10 to 15 times to obtain a nano-collagen solution;

[0065] S22. The pH value of the nano-collagen solution is adjusted to 8.5-9.0 with 0.1 mol / L sodium hydroxide solution, and chlorosulfonic acid is slowly added at 0-4°C, and the reaction is continued with stirring for 4-6 hours, and then the pH value is adjusted to 7.0-7.5 to obtain a third mixed solution;

[0066] S23. The third mixed solution is transferred to a dialysis bag and dialyzed in a phosphate buffered saline for 36 to 48 hours, with the phosphate buffered saline being replaced every 12 hours. After the dialysis is completed, a fourth mixed solution is obtained;

[0067] S24. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are slowly added dropwise to the fourth mixed solution for ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. After ultrasonic treatment for 0.5 to 1 h at room temperature, growth factors are added, and the reaction is continued with stirring at 0 to 4° C. for 24 to 30 h to obtain a fifth mixed solution;

[0068] S25. The fifth mixed solution is transferred to a dialysis bag, and dialyzed in a phosphate buffered saline at 0 to 4°C for 48 to 52 hours, with the phosphate buffered saline being replaced every 12 hours, to obtain a modified nano-collagen solution after the dialysis is completed;

[0069] S26. Freeze-dry the modified nano-collagen solution at a drying temperature of -40 to -60°C. After drying for 12 to 18 hours, the modified nano-collagen is obtained and ground into powder for later use.

[0070] The modified nano collagen is coupled with growth factors and contains sulfate groups on the surface, with a particle size of 45 to 65 nm and a specific surface area of ​​120 to 180 m 2 / g.

[0071] The mass ratio of the collagen, chlorosulfonic acid and growth factor is 1:(0.05-0.1):(0.02-0.05).

[0072] A preparation method of a gynecological vaginal mucosa repair gel, applied to the gynecological vaginal mucosa repair gel, comprises the following steps:

[0073] S31. Add purified water to the container, add carbomer to the container, stir evenly, then add glycerin, sodium hyaluronate, vitamin E and potassium sorbate in sequence and stir, while heating in a water bath at a temperature of 70 to 80 ° C until fully dissolved to obtain a sixth mixed solution;

[0074] S32. Wash and dry aloe, astragalus, dandelion, saffron and ginseng, crush and add purified water and 60-80% ethanol, place in an ultrasonic extractor, extract at 55-65°C, extract for 2-4h to obtain a first extract;

[0075] S33. Purified water and 60-80% ethanol were added again to continue extraction, twice in a row, to obtain a second extract and a third extract, respectively, and the extracts were mixed and concentrated under reduced pressure to obtain a composite extract of Chinese herbal medicine;

[0076] S34. The tea tree essential oil, albumin, modified nano collagen and Chinese herbal compound extract are sequentially added to the sixth mixed solution under stirring, and the modified nano polylactic acid-glycolic acid copolymer is added after stirring for 0.5 to 1 h, and the stirring is continued for 2 to 4 h to obtain a sixth mixed solution;

[0077] S35. Transfer the sixth mixed solution to a high-pressure homogenizer, set the pressure to 800-1000 bar, and filter through a 0.22 μm filter membrane after circulating 5-10 times. Put the filtered gynecological vaginal mucosa repair gel into a sterile container, and store it in a sealed and cool dry place.

[0078] The temperature of the reduced pressure concentration is 55-65° C. and the pressure is 0.5-0.8 bar.

[0079] The method of using the gynecological vaginal mucosa repair gel is as follows: wash your hands, gently insert the gel device into the vagina, push the gel device, slowly squeeze the gel into the patient's vagina, lie on your back for 6 to 8 minutes, and a course of treatment is 7 to 9 days, depending on the degree of recovery of the injury.

[0080] Example 2: This example discloses a gynecological vaginal mucosa repair gel, comprising the following raw materials in parts by weight: 6 parts of carbomer, 2 parts of glycerol, 1 part of sodium hyaluronate, 1 part of vitamin E, 0.5 parts of potassium sorbate, 0.2 parts of modified nano collagen, 0.2 parts of albumin, 0.5 parts of tea tree essential oil, 2 parts of aloe, 1 part of astragalus, 2 parts of dandelion, 1 part of saffron, and 1 part of ginseng. The gynecological vaginal mucosa repair gel also includes a modified nano polylactic acid-glycolic acid copolymer, and the modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1:6. The modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it. The particle size of the modified nano polylactic acid-glycolic acid copolymer is 80-100 nm, and the specific surface area is 50-80 m 2 / g. The preparation methods of the modified nano polylactic acid-glycolic acid copolymer and the modified nano collagen in this embodiment are consistent with those in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this embodiment is consistent with that in Example 1.

[0081] Example 3: This example discloses a gynecological vaginal mucosa repair gel, comprising the following raw materials in parts by weight: 12 parts of carbomer, 5 parts of glycerol, 2 parts of sodium hyaluronate, 2 parts of vitamin E, 1 part of potassium sorbate, 1 part of modified nano collagen, 1 part of albumin, 1 part of tea tree essential oil, 4 parts of aloe, 2 parts of astragalus, 3 parts of dandelion, 2 parts of saffron, and 2 parts of ginseng. The gynecological vaginal mucosa repair gel also includes a modified nano polylactic acid-glycolic acid copolymer, and the modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1:12. The modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it. The particle size of the modified nano polylactic acid-glycolic acid copolymer is 80-100 nm, and the specific surface area is 50-80 m 2 / g. The preparation methods of the modified nano polylactic acid-glycolic acid copolymer and the modified nano collagen in this embodiment are consistent with those in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this embodiment is consistent with that in Example 1.

[0082] Control group 1: The difference between this embodiment and embodiment 1 is that modified nano polylactic acid-glycolic acid copolymer is not contained. This embodiment discloses a gynecological vaginal mucosa repair gel, 9 parts of carbomer, 3 parts of glycerol, 1.5 parts of sodium hyaluronate, 1.5 parts of vitamin E, 0.8 parts of potassium sorbate, 0.6 parts of modified nano collagen, 0.6 parts of albumin, 0.8 parts of tea tree essential oil, 3 parts of aloe, 1.5 parts of astragalus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The preparation method of the modified nano collagen in this embodiment is consistent with that in embodiment 1. The preparation method of a gynecological vaginal mucosa repair gel in this embodiment is consistent with that in embodiment 1.

[0083] Control group 2: The difference between this embodiment and embodiment 1 is that modified nano collagen is not contained. This embodiment discloses a gynecological vaginal mucosa repair gel, which includes 9 parts of carbomer, 3 parts of glycerin, 1.5 parts of sodium hyaluronate, 1.5 parts of vitamin E, 0.8 parts of potassium sorbate, 0.6 parts of albumin, 0.8 parts of tea tree essential oil, 3 parts of aloe, 1.5 parts of astragalus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel also includes a modified nano polylactic acid-glycolic acid copolymer, and the modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1:9. The modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it. The particle size of the modified nano polylactic acid-glycolic acid copolymer is 80-100nm, and the specific surface area is 50-80m 2 / g. The preparation method of the modified nano polylactic acid-glycolic acid copolymer in this embodiment is consistent with that in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this embodiment is consistent with that in Example 1.

[0084] Control group 3: The difference between this embodiment and embodiment 1 is that albumin is not contained. This embodiment discloses a gynecological vaginal mucosa repair gel, comprising 9 parts of carbomer, 3 parts of glycerol, 1.5 parts of sodium hyaluronate, 1.5 parts of vitamin E, 0.8 parts of potassium sorbate, 0.6 parts of modified nano collagen, 0.8 parts of tea tree essential oil, 3 parts of aloe vera, 1.5 parts of astragalus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel also includes a modified nano polylactic acid-glycolic acid copolymer, wherein the modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1:9, wherein the modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it, wherein the particle size of the modified nano polylactic acid-glycolic acid copolymer is 80 to 100 nm, and the specific surface area is 50 to 80 m 2 / g. The preparation methods of the modified nano polylactic acid-glycolic acid copolymer and the modified nano collagen in this embodiment are consistent with those in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this embodiment is consistent with that in Example 1.

[0085] Effect evaluation: The vaginal tissue injury animal model was used to investigate the recovery of the injured area of ​​rats after using the gynecological vaginal mucosal repair gel. 42 adult healthy female rats, weighing 200-250g, aged 8-10 weeks, without specific pathogens, were provided by Hunan Slake Jingda Experimental Animal Company. All experimental rats were cultured for 7 days under the conditions of temperature (22±2)℃, humidity 50%±10%, noise below 85dB, and 12h light and dark cycle, with free drinking water and food to ensure their good health. After 7 days of feeding, the rats were randomly divided into 7 groups, with 6 rats in each group.

[0086] Modeling of vaginal tissue injury rats: fast for 12 hours before treatment, first use 1% sodium pentobarbital injection to anesthetize the rats, soak a 3mm diameter cotton swab in 80% trichloroacetic acid solution and gently insert it into the vagina to a depth of about 2cm, gently apply it on the vaginal wall for 10 seconds, and then immediately rinse the vagina with saline for 3 times. During the modeling process, observe the changes in the vaginal tissue of all rats. If there is redness of the vaginal opening, local edema, and slight bleeding symptoms, it means that the modeling is successful. Figure 3 As shown in (a), the submucosal layer of the vaginal tissue of the rat showed obvious edema, enlarged tissue gaps, fiber separation, inflammatory cell infiltration, and partial shedding of surface epithelial cells, showing obvious symptoms of vaginal tissue damage. 24 hours after the model was completed, the rats in each experimental group were administered according to the method of use of the gynecological vaginal mucosal repair gel, twice a day, about 0.2g each time, for 9 days, ensuring that other feeding conditions were the same, and the blank group was not administered, and was given 0.9% sodium chloride solution according to the above administration method.

[0087] The pathological changes of vaginal tissue in rats with vaginal tissue injury were analyzed by the changes of body weight and total white blood cell count of rats. The specific method is as follows: observe and record the body weight of rats in each group before and after treatment; after continuous treatment for 9 days, 2 rats were randomly selected from each experimental group on the 10th day for eyeball blood collection, and the total white blood cell count was determined by microscopic counting. After the treatment, one rat was randomly selected from Example 1 and anesthetized and killed, and tissue sampling was performed to observe the physiological changes of vaginal tissue cells. The specific method is as follows: tissue from the vagina to the uterine angle of each group of rats was taken to observe the tissue edema, and the tissue was fixed in 4% paraformaldehyde, embedded in paraffin, sliced, and stained with hematoxylin-eosin, and the pathological changes of the tissue were examined under a microscope. The changes in body weight and total white blood cell count of rats in each experimental group before and after treatment are shown in Table 1, and the recovery of vaginal tissue of rats in each experimental group was recorded by naked eye observation on the 1st, 3rd, 6th and 9th days and statistically shown in Table 2.

[0088] Table 1 Statistical table of changes in body weight and total white blood cell count of rats before and after treatment

[0089]

[0090] As can be seen from Table 1, after 9 days of treatment, the body weight of the rats in the blank group without medication was significantly lower than that of the rats in other experimental groups, and the total number of white blood cells in the blood was also much higher than that of the rats in other experimental groups, indicating that the inflammatory response in the rats was severe, which reduced the rats' appetite and food intake. Comparing the body weight and the total number of white blood cells of the rats in the experimental groups of Examples 1 to 3, it was found that the body weight of the rats in Example 1 changed the most and the total number of white blood cells was the least, indicating that the gynecological vaginal mucosa repair gel prepared by the drug formula of Example 1 was the most effective, and its efficacy was significantly higher than that of the other experimental groups, such as Figure 3 As shown in (b), the epidermal cells and mucosal cells of the rat vaginal tissue returned to normal arrangement, without abnormal proliferation or inflammatory cell infiltration, and the structures of the muscle layer, epithelial layer and submucosal layer of the vaginal wall were intact without damage marks. The body weight and total leukocyte count of the rats in the experimental groups of Example 1 and the control groups 1 to 3 were compared, and it was found that when the three drugs of modified nano polylactic acid-glycolic acid copolymer, albumin and modified nano collagen were simultaneously present in the gynecological vaginal mucosa repair gel, the efficacy of the gynecological vaginal mucosa repair gel was better, indicating that the three substances of modified nano polylactic acid-glycolic acid copolymer, albumin and modified nano collagen had a synergistic effect in the gynecological vaginal mucosa repair gel.

[0091] According to the symptoms of the recovery of the vaginal tissue injury model rats, they are divided into 5 levels, namely no relief (A), mild relief (B), moderate relief (C), almost cured (D) and completely cured (E), specifically as follows:

[0092] No relief (A): There was no significant improvement in vaginal tissue damage. The vaginal mucosal epithelium was degenerated and necrotic, and the thickness was extremely thin. A large number of inflammatory cells were seen infiltrating under the mucosa. Vaginal secretions were abnormal, showing thin, light yellow or purulent blood. Rats showed symptoms such as vulvar burning discomfort, itching and pain, and vaginal dryness.

[0093] Mild relief (B): Vaginal tissue damage began to ease, but the improvement was not obvious. The thickness of the vaginal mucosal epithelium increased, but it was still thin. The infiltration of submucosal inflammatory cells decreased. Vaginal secretions still showed a certain degree of abnormality, but it was improved compared with before. The vaginal discomfort symptoms of rats were alleviated, but they were still noticeable.

[0094] Moderate relief (C): Vaginal tissue damage was significantly alleviated, the thickness of the vaginal mucosal epithelium was close to normal, the submucosal inflammatory cell infiltration was significantly reduced, vaginal secretions basically returned to normal, with no obvious abnormalities, and the vaginal discomfort symptoms of the rats basically disappeared.

[0095] Almost cured (D): The vaginal tissue damage has been significantly restored and is close to normal. The vaginal mucosal epithelial structure is intact and the thickness is normal. There is no inflammatory cell infiltration under the mucosa. The vaginal secretions are completely normal and there are no abnormal manifestations. The vaginal function of the rats has basically returned to normal and there are no discomfort symptoms.

[0096] Complete recovery (E): Vaginal tissue damage is completely restored and is no different from that of normal rats. The structure, thickness and function of the vaginal mucosal epithelium have returned to normal. Physiological indicators such as vaginal secretions and pH value are all within the normal range. The vaginal function of the rats is completely restored without any discomfort.

[0097] Table 2 Statistical results of recovery of rats with vaginal tissue injury model

[0098] Group Day 1 Day 3 Day 6 Day 9 Example 1 AAAAAA CCCCBB DDDDCD EEEEEE Example 2 AAAAAA BCBCBC CDCD DEDEEE Example 3 AAAAAA CBBCCC DCCDDD EDDEEE Control group 1 AAAAAA BBBAAB DCCBBC EDDCDD Control group 2 AAAAAA BBABAA CCBCBB DDCECC Control group 3 AAAAAA AABBBB BBCCDC CCDDEC Blank Group AAAAAA AABAAA AABABB AABBBB

[0099] Table 2 is the statistical results of the recovery of the vaginal tissue injury model rats in each experimental group. It can be seen from Table 2 that the vaginal tissue injury of the rats in the blank group without medication was almost not significantly improved, and when the gynecological vaginal mucosa repair gel prepared in Example 1 was used on the injured part of the rats, the recovery of the rats was the best. From the 3rd day, the 6th day to the end of the 9th day of the treatment, the recovery of the rats was better than that of the other experimental groups, showing excellent drug efficacy. By comparing Examples 1 to 3 with Control Groups 1 to 3, it can be found that the recovery of the rats in Examples 1 to 3 is also significantly better than that in Control Groups 1 to 3, which shows that by adding the three substances of modified nano-polylactic acid-glycolic acid copolymer, albumin and modified nano-collagen at the same time during the gel preparation process, a gynecological vaginal mucosa repair gel with excellent repair performance can be obtained.

[0100] Through the above limited experiments, the application effect of the gynecological vaginal mucosa repair gel of Example 1 of the present invention is significant. By adding the three substances of modified nano polylactic acid-glycolic acid copolymer, albumin and modified nano collagen at the same time during the production process, the cell tissue repair and regeneration function of the gynecological vaginal mucosa repair gel can be significantly enhanced. At the same time, the drug release rate is adjusted according to the pH value changes of the physiological environment, the bioavailability of the drug is improved, the inflammatory response is reduced, an immune microenvironment conducive to tissue repair is created, and the cell tissue repair and regeneration process is accelerated, so that the vaginal tissue can quickly return to normal levels.

[0101] Finally, it should be noted that: Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A gynecological vaginal mucosa repair gel, characterized in that: The invention comprises the following raw materials in parts by weight: 6-12 parts of carbomer, 2-5 parts of glycerin, 1-2 parts of sodium hyaluronate, 1-2 parts of vitamin E, 0.5-1 parts of potassium sorbate, 0.2-1 parts of modified nano collagen, 0.2-1 parts of albumin, 0.5-1 parts of tea tree essential oil, 2-4 parts of aloe vera, 1-2 parts of astragalus, 2-3 parts of dandelion, 1-2 parts of saffron and 1-2 parts of ginseng; The gynecological vaginal mucosa repair gel also includes: Modified nano polylactic acid-glycolic acid copolymer; The modified nano polylactic acid-glycolic acid copolymer and carbomer are in a weight ratio of 1: (6-12); The modified nano polylactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of the polylactic acid-glycolic acid copolymer and then nano-crystallizing it; The modified nano polylactic acid-glycolic acid copolymer has a particle size of 80 to 100 nm and a specific surface area of ​​50 to 80 m 2 / g.

2. A gynecological vaginal mucosa repair gel according to claim 1, characterized in that: The preparation method of the modified nano polylactic acid-glycolic acid copolymer comprises: S11. Slowly adding the polylactic acid-glycolic acid copolymer to anhydrous dichloromethane under stirring, stirring for 0.5 to 1 h, and then filtering with a 0.22 μm filter membrane to obtain a polylactic acid-glycolic acid copolymer solution; S12. dissolving polyacrylic acid in purified water under stirring, stirring for 0.5 to 1 h, and then adjusting the pH value to 4.5 to 5.0 with 0.1 mol / L dilute hydrochloric acid solution to obtain a polyacrylic acid solution; S13. slowly dropwise adding the polylactic acid-co-glycolic acid solution into the polyvinyl alcohol aqueous solution for ultrasonic treatment and setting the pulse mode to an ultrasonic frequency of 40 to 50 kHz, and then slowly adding the polyacrylic acid solution after ultrasonic treatment at room temperature for 15 to 30 minutes, and continuing the ultrasonic treatment for 10 to 20 minutes to obtain a first mixed solution; S14. The first mixed solution was transferred to a magnetic stirrer at a speed of 500 to 800 rpm and stirred at room temperature for 6 to 8 hours to obtain a second mixed solution; S15. The second mixed solution was subjected to high-speed centrifugation at a speed of 12000 to 15000 rpm for 15 to 20 min, and the separated solid was washed three times with phosphate buffered saline and then freeze-dried; S16. After the solid is precooled at -60 to -80°C for 2 to 4 hours, the freeze-drying temperature is set to -40 to -50°C, and after drying for 24 to 30 hours, the modified nano polylactic acid-glycolic acid copolymer is obtained and ground into powder for later use.

3. A gynecological vaginal mucosa repair gel according to claim 2, characterized in that: The mass ratio of the polylactic acid-glycolic acid copolymer to polyacrylic acid is 1:(0.1-0.2).

4. The gynecological vaginal mucosa repair gel according to claim 1, characterized in that: The preparation method of the modified nano collagen comprises: S21. Dissolve collagen in acetic acid, stir at room temperature for 0.5 to 1 h, transfer to a high-pressure homogenizer, set the pressure to 800 to 1000 bar, and cycle 10 to 15 times to obtain a nano-collagen solution; S22. The pH value of the nano-collagen solution is adjusted to 8.5-9.0 with 0.1 mol / L sodium hydroxide solution, and chlorosulfonic acid is slowly added at 0-4°C, and the reaction is continued with stirring for 4-6 hours, and then the pH value is adjusted to 7.0-7.5 to obtain a third mixed solution; S23. The third mixed solution is transferred to a dialysis bag and dialyzed in a phosphate buffered saline for 36 to 48 hours, with the phosphate buffered saline being replaced every 12 hours. After the dialysis is completed, a fourth mixed solution is obtained; S24. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are slowly added dropwise to the fourth mixed solution for ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. After ultrasonic treatment for 0.5 to 1 h at room temperature, growth factors are added, and the reaction is continued with stirring at 0 to 4° C. for 24 to 30 h to obtain a fifth mixed solution; S25. The fifth mixed solution is transferred to a dialysis bag, and dialyzed in a phosphate buffered saline at 0 to 4°C for 48 to 52 hours, with the phosphate buffered saline being replaced every 12 hours, to obtain a modified nano-collagen solution after the dialysis is completed; S26. Freeze-dry the modified nano-collagen solution at a drying temperature of -40 to -60°C. After drying for 12 to 18 hours, the modified nano-collagen is obtained and ground into powder for later use.

5. The gynecological vaginal mucosa repair gel according to claim 4, characterized in that: The modified nano collagen is coupled with growth factors and contains sulfate groups on the surface, with a particle size of 45 to 65 nm and a specific surface area of ​​120 to 180 m 2 / g.

6. The gynecological vaginal mucosa repair gel according to claim 4, characterized in that: The mass ratio of the collagen, chlorosulfonic acid and growth factor is 1:(0.05-0.1):(0.02-0.05).

7. A method for preparing a gynecological vaginal mucosa repair gel, which is used to prepare the gynecological vaginal mucosa repair gel as claimed in any one of claims 1 to 6, characterized in that: The method comprises the following steps: S31. Add purified water to the container, add carbomer to the container, stir evenly, then add glycerin, sodium hyaluronate, vitamin E and potassium sorbate in sequence and stir, while heating in a water bath at a temperature of 70 to 80 ° C until fully dissolved to obtain a sixth mixed solution; S32. Wash and dry aloe, astragalus, dandelion, saffron and ginseng, crush and add purified water and 60-80% ethanol, place in an ultrasonic extractor, extract at 55-65°C, extract for 2-4h to obtain a first extract; S33. Purified water and 60-80% ethanol were added again to continue extraction, twice in a row, to obtain a second extract and a third extract, respectively, and the extracts were mixed and concentrated under reduced pressure to obtain a composite extract of Chinese herbal medicine; S34. The tea tree essential oil, albumin, modified nano collagen and Chinese herbal compound extract are sequentially added to the sixth mixed solution under stirring, and the modified nano polylactic acid-glycolic acid copolymer is added after stirring for 0.5 to 1 h, and the stirring is continued for 2 to 4 h to obtain a sixth mixed solution; S35. Transfer the sixth mixed solution to a high-pressure homogenizer, set the pressure to 800-1000 bar, and filter through a 0.22 μm filter membrane after circulating 5-10 times. Put the filtered gynecological vaginal mucosa repair gel into a sterile container, and store it in a sealed and cool dry place.

8. The method for preparing a gynecological vaginal mucosa repair gel according to claim 7, characterized in that: The temperature of the reduced pressure concentration is 55-65° C. and the pressure is 0.5-0.8 bar.

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