A gynecological vaginal mucosa repair gel and its preparation method

Abstract

The present invention relates to the technical field of medical gels, and specifically relates to a gynecological vaginal mucosa repair gel and a preparation method thereof, comprising the following raw materials: carbomer, glycerol, sodium hyaluronate, vitamin E, potassium sorbate, modified nano poly(lactic-co-glycolic acid), modified nano collagen, albumin, tea tree essential oil, aloe vera, astragalus membranaceus, dandelion, saffron and ginseng. In the present invention, the modified nano poly(lactic-co-glycolic acid), modified nano collagen and albumin act through a synergistic effect. The modified nano poly(lactic-co-glycolic acid) serves as a framework structure for cell growth and firmly attaches the drug active ingredient-albumin complex. The polyacrylic acid chains on its surface control the drug release rate by sensing pH value changes. Albumin initiates endocytosis through specific binding and, together with the modified nano collagen, improves the anti-inflammatory performance, promotes cell proliferation and differentiation, and promotes the repair and regeneration of vaginal mucosa tissue.

Description

Technical Field

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

[0002] In the field of women's health, vaginal mucosal injury is a common disease, and its causes are numerous, including physiological factors, infectious factors, improper behaviors, and iatrogenic factors, etc. For example, during menstruation, the vaginal mucosa is easily damaged due to hormonal effects, infections such as bacterial, fungal, or trichomonal vaginitis can cause mucosal inflammation and injury, and improper behaviors such as frequent use of vaginal douches or tampons can all lead to mucosal damage. Due to these reasons, vaginal mucosal injury has a relatively high incidence rate among women. For this disease, local drug treatment is an important treatment method, which can directly act on the damaged mucosa, increase the drug concentration, and avoid the side effects caused by oral drug treatment and systemic treatment. As a locally applied drug product, the gynecological vaginal mucosa repair gel has many advantages. It can directly act on the damaged mucosa and is convenient to use. Its good bioadhesion can keep it on the mucosal surface for a long time, which is beneficial to the continuous release and absorption of drugs, improves the drug utilization rate, and has excellent biocompatibility, which can effectively reduce the 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 mucosa repair gel. However, at present, the gynecological vaginal mucosa repair gel still has some disadvantages and deficiencies in cell tissue repair and regeneration, and needs to be further improved. 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 value change of the physiological environment, so as to 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 soon.

[0003] (1) Technical Problems 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 soon.

[0005] (2) Technical Solutions

[0006] To achieve the above object, on the one hand, the present invention provides a gynecological vaginal mucosa repair gel, which comprises the following raw materials in parts by weight: 6-12 parts of carbomer, 2-5 parts of glycerol, 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 vera, 1-2 parts of astragalus membranaceus, 2-3 parts of dandelion, 1-2 parts of saffron, 1-2 parts of ginseng;

[0007] Modified nano poly lactic acid-glycolic acid copolymer;

[0008] The weight ratio of the modified nano poly lactic acid-glycolic acid copolymer to carbomer is 1:(6-12);

[0009] The modified nano poly lactic acid-glycolic acid copolymer is obtained by grafting polyacrylic acid on the surface of poly lactic acid-glycolic acid copolymer and then nano-sizing;

[0010] The particle size of the modified nano poly lactic acid-glycolic acid copolymer is 80-100 nm, and the specific surface area is 50-80 m 2 / g.

[0011] Further, the preparation method of the modified nano poly lactic acid-glycolic acid copolymer comprises:

[0012] S11. Under stirring, slowly add poly lactic acid-glycolic acid copolymer into anhydrous dichloromethane, stir for 0.5-1 h, and then filter with a 0.22 μm filter membrane to obtain a poly lactic acid-glycolic acid copolymer solution;

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

[0014] S13. Slowly drop the poly lactic acid-glycolic acid copolymer solution into an aqueous solution of polyvinyl alcohol for ultrasonic treatment and set the pulse mode, with an ultrasonic frequency of 40-50 kHz. After ultrasonic treatment at room temperature for 15-30 min, slowly add the polyacrylic acid solution, and continue ultrasonic treatment for 10-20 min to obtain a first mixed solution;

[0015] S14. Transfer the first mixed solution to a magnetic stirrer, with a rotation speed of 500-800 rpm, and stir at room temperature for 6-8 h to obtain a second mixed solution;

[0016] S15. Centrifuge the second mixed solution at a high speed, with a rotation speed of 12000-15000 rpm, centrifuge for 15-20 min, wash the separated solid 3 times with phosphate buffered saline, and then perform freeze-drying;

[0017] S16. After pre-cooling the solid at -60 to -80 °C for 2 to 4 h, set the freeze-drying temperature to -40 to -50 °C. After drying for 24 to 30 h, the modified nano poly(lactic-co-glycolic acid) copolymer is obtained and ground into powder for standby.

[0018] Further, the mass ratio of the poly(lactic-co-glycolic acid) copolymer to polyacrylic acid is 1:(0.1 - 0.2).

[0019] Further, the preparation method of the modified nano collagen includes:

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

[0021] S22. Adjust the pH value of the nano collagen solution to 8.5 - 9.0 with 0.1 mol / L sodium hydroxide solution. At 0 to 4 °C, slowly add chlorosulfonic acid and continue to stir and react for 4 to 6 h, then adjust the pH value to 7.0 - 7.5 to obtain a third mixed solution.

[0022] S23. Transfer the third mixed solution into a dialysis bag and dialyze it in phosphate buffered saline for 36 to 48 h, changing the phosphate buffered saline every 12 h. After dialysis, a fourth mixed solution is obtained.

[0023] S24. Slowly drop 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide into the fourth mixed solution for ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz. After ultrasonic treatment at room temperature for 0.5 to 1 h, add growth factors and continue to stir and react at 0 to 4 °C for 24 to 30 h to obtain a fifth mixed solution.

[0024] S25. Transfer the fifth mixed solution into a dialysis bag and dialyze it in phosphate buffered saline at 0 to 4 °C for 48 to 52 h, changing the phosphate buffered saline every 12 h. After dialysis, a modified nano collagen solution is obtained.

[0025] S26. Freeze-dry the modified nano collagen solution. The drying temperature is -40 to -60 °C. After drying for 12 to 18 h, the modified nano collagen is obtained and ground into powder for standby.

[0026] Further, the modified nano collagen is conjugated with growth factors and has sulfate groups on its surface. Its particle size is 45 - 65 nm and its specific surface area is 120 - 180 m 2 / g.

[0027] Further, 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 preparation method of a gynecological vaginal mucosa repair gel, which is applied to the above-mentioned gynecological vaginal mucosa repair gel, and includes the following steps:

[0029] S31. Add purified water into a container, add carbomer into the container, stir evenly, and then sequentially add glycerol, sodium hyaluronate, vitamin E and potassium sorbate and stir, while heating in a water bath, the heating temperature is 70 - 80 °C until completely dissolved to obtain a sixth mixed solution;

[0030] S32. Wash aloe vera, astragalus membranaceus, dandelion, saffron and ginseng, dry them, crush them, add purified water and 60 - 80% ethanol, and place them in an ultrasonic extractor. The extraction temperature is 55 - 65 °C, and after extraction for 2 - 4 h, a first extract is obtained;

[0031] S33. Add purified water and 60 - 80% ethanol again for continuous extraction twice, respectively obtaining a second extract and a third extract. After mixing the extracts, perform vacuum concentration to obtain a Chinese herbal medicine composite extract;

[0032] S34. Under the stirring state, sequentially add tea tree essential oil, albumin, modified nano - collagen and the Chinese herbal medicine composite extract into the sixth mixed solution, stir for 0.5 - 1 h, then add modified nano - poly(lactic - co - glycolic acid), and continue to stir for 2 - 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, circulate 5 - 10 times, then filter through a 0.22 μm filter membrane, and fill the filtered gynecological vaginal mucosa repair gel into a sterile container, and store it sealed in a cool and dry place.

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

[0035] Further, the usage method of the above - mentioned gynecological vaginal mucosa repair gel is as follows: Wash hands, gently insert the gel applicator into the vagina, push the gel applicator, slowly squeeze the gel into the patient's vagina, lie supine for 6 - 8 min, and 7 - 9 days is a treatment course, depending on the degree of injury recovery.

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

[0037] Carbomer is a kind of polymer, which has the functions of thickening, suspending and stabilizing, and is commonly used as a drug thickener and emulsifier. Glycerol is a simple polyol compound. Since it has three hydroxyl groups (-OH), it can be miscible with water, has hygroscopicity, and has good permeability. In the repair gel, glycerol can relieve vaginal dryness, reduce itching and discomfort, and also helps to protect the skin. Sodium hyaluronate is a linear polysaccharide composed of alternating D-glucuronic acid and N-acetyl-D-glucosamine, containing a large number of hydroxyl groups (-OH) and carboxyl groups (-COOH), with good biocompatibility, and is a powerful moisturizing ingredient, which helps to repair and moisten the vaginal mucosa. Vitamin E is an antioxidant, which can protect cells from oxidative stress damage, reduce inflammatory reactions, relieve tissue irritation, and accelerate the repair process of the skin and mucosa. Potassium sorbate is a commonly used preservative, which can inhibit the growth of microorganisms and improve the product stability, making the product maintain high activity within a wide pH range and extending the product shelf life.

[0038] The main chemical components of tea tree essential oil are terpene compounds, which can destroy the cell membrane structure of microorganisms, interfere with the energy metabolism process of microorganisms, have significant inhibitory effects on bacteria, fungi and certain viruses, while reducing local inflammatory reactions, relieving discomfort symptoms, and accelerating the repair process of the skin and mucosa. Aloe mainly includes various active ingredients such as polysaccharides, anthraquinones, amino acids, vitamins and minerals, has a moisturizing effect, can relieve the skin and reduce mucosal irritation, while promoting wound healing, reducing scar formation, and enhancing local immunity. Astragalus membranaceus is a common traditional Chinese medicine with antioxidant and anti-inflammatory effects. Its main components 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 taraxasterol, chlorogenic acid and flavonoid compounds, which can promote the excretion 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 are crocetin, crocin and kaempferol, etc., which can improve blood circulation, promote tissue repair and regeneration, reduce local inflammatory reactions, regulate the concentrations of serotonin and dopamine, regulate emotions, and improve the mental state. The main active ingredients of ginseng are ginsenosides, ginseng polysaccharides and ginseng alcohols, etc., which can regulate immune function, enhance the activities of T cells and NK cells, improve the body's resistance, while enhancing mitochondrial function, promoting energy metabolism, and accelerating the repair and regeneration of cell tissues.

[0039] Albumin is the most abundant protein in human plasma and is mainly synthesized by the liver. In the gynecological vaginal mucosal repair gel, it exhibits various functions 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 is the main component of connective tissue, with excellent biocompatibility and low immunogenicity. By nanosizing collagen and introducing sulfate groups and coupling growth factors onto its surface through chemical modification, modified nano-collagen is obtained. Modified nano-collagen shows unique advantages in promoting epithelial cell regeneration, regulating the vaginal microenvironment, and regulating immune responses. Poly(lactic-co-glycolic acid) is a biodegradable polymer material formed by the polymerization of two monomers, lactic acid and glycolic acid, through an esterification reaction. Due to its good biocompatibility and controllable degradability, it is used in various biomedical applications such as drug delivery systems and tissue engineering scaffolds. By nanosizing poly(lactic-co-glycolic acid) and grafting pH-sensitive polyacrylic acid polymers onto its surface, modified nano-poly(lactic-co-glycolic acid) is obtained, further enhancing the functionality of modified nano-poly(lactic-co-glycolic acid) and enabling it to adjust the drug release rate according to the change in the pH value of the vaginal physiological environment.

[0040] In the gynecological vaginal mucosa repair gel, the modified nano poly(lactic-co-glycolic acid), modified nano collagen, and albumin act through a synergistic effect. When preparing the gynecological vaginal mucosa repair gel, albumin forms a stable drug active ingredient-albumin complex with drug active ingredients such as modified nano collagen and Chinese herbal medicine compound extract through its hydrophilicity and hydrophobicity. The modified nano poly(lactic-co-glycolic acid) prepared by the emulsion-solvent evaporation method can be used as a drug sustained-release carrier due to its high specific surface area and rich pore structure, and through physical adsorption and chemical action, it interacts with these drug active ingredient-albumin complexes to firmly attach them to the porous structure of the modified nano poly(lactic-co-glycolic acid), and at the same time provides a stable microenvironment for the drug active ingredients. Under normal physiological conditions, the pH value of the vaginal environment is between 3.8 and 4.5, but when there are inflammations, vaginal mucosa tissue damage, etc., the pH value of the vaginal environment will increase. When this gynecological vaginal mucosa repair gel acts on the damaged vaginal tissue mucosa, the modified nano poly(lactic-co-glycolic acid) senses the pH value change, and the polyacrylic acid side chain on its surface will be protonated, causing the modified nano poly(lactic-co-glycolic acid) particles to swell, thereby accelerating drug release and timely releasing more drug active ingredient-albumin complexes. At the same time, albumin specifically binds to the albumin receptor on the surface of the vaginal epithelial cells at the injury site, triggering receptor-mediated endocytosis, so that the drug active ingredient-albumin complex is directly swallowed by the cells to form inner vesicles. Under the action of lysosomes, the drug active ingredient-albumin complex is decomposed, releasing drug components such as modified nano collagen and traditional Chinese medicine active components. The sulfate groups on the surface of the modified nano collagen better bind and stabilize growth factors by mimicking sulfated glycosaminoglycans in the extracellular matrix, and at the same time enhance the interaction with damaged cells, and together with albumin, improve the anti-inflammatory performance of the body. The 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 aggregation that occurs when the modified nano poly(lactic-co-glycolic acid) and modified nano collagen coexist, protecting the structural integrity of the modified nano poly(lactic-co-glycolic acid) and modified nano collagen. With the natural metabolism of the human body, the modified nano poly(lactic-co-glycolic acid) 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 poly(lactic-co-glycolic acid) particles themselves can serve as the skeletal structure for cell growth, creating a good immune microenvironment for the repair of tissue cells, and jointly promoting the repair and regeneration of the vaginal mucosa tissue with drug components such as albumin, modified nano collagen, and traditional Chinese medicine active components.

[0041] (3) Beneficial effects

[0042] Compared with the prior art, the beneficial effects of the present invention are:

[0043] 1. The modified nano-poly(lactic-co-glycolic acid), modified nano-collagen, and albumin act synergistically. Albumin forms a stable drug active ingredient-albumin complex with drug active ingredients such as modified nano-collagen and compound herbal extracts through its hydrophilicity and hydrophobicity, and is firmly attached under the physical adsorption and chemical action of the modified nano-poly(lactic-co-glycolic acid).

[0044] 2. The polyacrylic acid side chains on the surface of the modified nano-poly(lactic-co-glycolic acid) control the drug release rate by sensing the change in the pH value of the vaginal environment. When there is inflammation, vaginal mucosal tissue damage, etc., which cause the pH value of the vaginal environment to increase, the release of the drug active ingredient-albumin complex is accelerated.

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

[0046] 4. The sulfate groups on the surface of the modified nano-collagen better bind and stabilize growth factors by mimicking sulfated glycosaminoglycans in the extracellular matrix, enhancing the interaction with damaged cells, and improving the anti-inflammatory performance of the body together with albumin. The 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-poly(lactic-co-glycolic acid) further promotes the synthesis of collagen at the injured tissue site, and serves as a skeletal structure for cell growth, creating a good immune microenvironment for the repair of tissue cells, and jointly promoting the repair and regeneration of vaginal mucosal tissue with drug components such as albumin, modified nano-collagen, and traditional Chinese medicine active components. Description of the Drawings

[0048] Figure 1 SEM image of the modified nano-poly(lactic-co-glycolic acid) in Example 1 of the present invention;

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

[0050] Figure 3 SEM images of the vaginal tissue of the rat with vaginal tissue injury model in Example 1 of the present invention before (a) and after (b) using the gynecological vaginal mucosal repair gel. Detailed Embodiments

[0051] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0052] The test equipment and preparations in the following embodiments are as follows: electronic balance (Sartorius, Germany), electrothermal constant temperature water bath (Kedao, Jiangsu), magnetic stirrer (Meiyingpu, Shanghai), ultrasonic instrument (Yixin, Shanghai), high-speed centrifuge (Jidi, Guangzhou), ultrasonic extractor (Jiemeng, Guangdong), dialysis instrument (Zhuyan, Jinan), vacuum homogenizing emulsifier (Nuoze, Shanghai), rotary evaporator (Yaote, Shanghai), scanning electron microscope (Zeiss, Germany), specific surface area analyzer (Beijing Beishide Instrument Technology), freeze dryer (Pudong Freeze Drying, Shanghai), pH meter (Yidian, Shanghai), variable magnification stereomicroscope (Olympus, Japan); Chinese medicinal materials were purchased from Tongrentang Pharmacy, and chemical drugs and reagents were purchased from Sigma-Aldrich.

[0053] Example 1: This example discloses a gynecological vaginal mucosa repair gel, including 9 parts of carbomer, 3 parts of glycerol, 1.5 parts of sodium hyaluronate, 1.5 parts of vitamin E, 0.8 part of potassium sorbate, 0.6 part of modified nano-collagen, 0.6 part of albumin, 0.8 part of tea tree essential oil, 3 parts of aloe vera, 1.5 parts of astragalus membranaceus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel further includes a modified nano-poly(lactic-co-glycolic acid) copolymer, and the weight ratio of the modified nano-poly(lactic-co-glycolic acid) copolymer to carbomer is 1:9. The modified nano-poly(lactic-co-glycolic acid) copolymer is obtained by grafting polyacrylic acid on the surface of poly(lactic-co-glycolic acid) and then nano-sizing. The particle size of the modified nano-poly(lactic-co-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, the modified nano-poly(lactic-co-glycolic acid) copolymer, modified nano-collagen, and albumin act through a synergistic effect. When preparing the gynecological vaginal mucosa repair gel, albumin is a multifunctional protein with a flexible structure, and there are multiple hydrophobic binding sites on its surface, such as Sudlow. At the same time, it is rich in charged amino acid residues and shows hydrophilicity. Drug active ingredients such as modified nano-collagen and Chinese herbal medicine compound extracts form stable drug active ingredient-albumin complexes with albumin through the hydrophilicity and hydrophobicity of albumin, such as Figure 1As shown, the modified nano-poly(lactic-co-glycolic acid) prepared by the emulsion-solvent evaporation method has a rich pore 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 drug active ingredient-albumin complex. At the same time, through electrostatic interaction and covalent interaction, these drug active ingredient-albumin complexes are firmly attached to the porous structure of the modified nano-poly(lactic-co-glycolic acid), and also provide a stable microenvironment for the drug active ingredient, protecting the drug from the external environment and maintaining the drug activity. Under normal physiological conditions, the pH value of the vaginal environment is between 3.8 and 4.5. However, when there are inflammations, vaginal mucosal tissue damage, etc., 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-poly(lactic-co-glycolic acid) senses the pH value change, and the carboxyl group (-COOH) of the polyacrylic acid side chain on its surface will be protonated and lose an H + to obtain a negatively charged carboxylate anion (-COO - ). The electrostatic repulsion between the negatively charged carboxylate anions (-COO - ) causes the carbon chain of the modified nano-poly(lactic-co-glycolic acid) to stretch, resulting in the expansion of the nanoparticles. At the same time, it weakens the electrostatic attraction with the positively charged albumin and drug active components, causing the drug active ingredient-albumin complex to dissociate from the porous structure of the modified nano-poly(lactic-co-glycolic acid), releasing the drug active ingredient-albumin complex. At the same time, albumin specifically binds to the albumin receptor on the surface of the vaginal epithelial cells at the injury site, triggering receptor-mediated endocytosis, so that the drug active ingredient-albumin complex is directly swallowed by the cells to form endosomes. Under the action of lysosomes, the drug active ingredient-albumin complex is decomposed, releasing drug components such as modified nano-collagen and traditional Chinese medicine active components. Figure 2SEM image of modified nano - collagen shows that the particle size of modified nano - collagen is uniform, the morphology is spherical and shows a certain fibrous structure. The sulfate groups (-SO3H) on the surface of modified nano - collagen increase the negative charge density of modified nano - collagen. By simulating sulfated glycosaminoglycans in the extracellular matrix, it enables better binding and stabilization of growth factors during the preparation of modified nano - collagen. At the same time, it also enhances the interaction with damaged cells, and together with albumin, improves the anti - inflammatory performance of the body, creating favorable conditions for tissue repair. The growth factors coupled on the surface of modified nano - collagen directly promote cell proliferation and differentiation, thus accelerating the repair and regeneration of cell tissues. In addition, the presence of albumin further avoids the aggregation that occurs when both modified poly (lactic - co - glycolic acid) nanoparticles and modified nano - collagen are present. Aggregation will cause the biological active sites of modified nano - collagen and modified poly (lactic - co - glycolic acid) nanoparticles to be blocked, and the large particles formed by aggregation will affect the uniformity of the distribution of drug active ingredients on the vaginal mucosa. At the same time, overly large nanoparticles are difficult to be taken up by cells, thus reducing their ability to promote cell attachment and growth. However, albumin protects the structural integrity of modified poly (lactic - co - glycolic acid) nanoparticles and modified nano - collagen. Albumin molecules adsorb 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 approach of modified poly (lactic - co - glycolic acid) nanoparticles through steric repulsion. With the natural metabolism of the human body, modified poly (lactic - co - glycolic acid) nanoparticles are gradually decomposed into lactic acid and glycolic acid and are absorbed and utilized by the human body. The released lactic acid further promotes the synthesis of collagen at the injured tissue site. At the same time, the modified poly (lactic - co - glycolic acid) nanoparticle itself can serve as a scaffold structure for cell growth, creating a good immune microenvironment for the repair of tissue cells, and jointly promoting the repair and regeneration of vaginal mucosa tissue with albumin, modified nano - collagen and traditional Chinese medicine active components and other drug components.

[0055] The preparation method of the modified poly (lactic - co - glycolic acid) nanoparticles includes:

[0056] S11. Slowly add poly (lactic - co - glycolic acid) copolymer into anhydrous dichloromethane under stirring. After stirring for 0.5 - 1 h, filter with a 0.22 μm filter membrane to obtain a poly (lactic - co - glycolic acid) copolymer solution;

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

[0058] S13. Slowly drop the poly(lactic-co-glycolic acid) copolymer solution into the aqueous polyvinyl alcohol solution, perform ultrasonic treatment and set the pulse mode, with an ultrasonic frequency of 40 - 50 kHz. After ultrasonic treatment at room temperature for 15 - 30 min, slowly add the polyacrylic acid solution, and continue ultrasonic treatment for 10 - 20 min to obtain the first mixed solution;

[0059] S14. Transfer the first mixed solution to a magnetic stirrer, with a rotation speed of 500 - 800 rpm, and stir at room temperature for 6 - 8 h to obtain the second mixed solution;

[0060] S15. Centrifuge the second mixed solution at a high speed, with a rotation speed of 12000 - 15000 rpm, centrifuge for 15 - 20 min. Wash the separated solid 3 times with phosphate buffered saline and then perform freeze-drying;

[0061] S16. After pre-cooling the solid at -60 - -80 °C for 2 - 4 h, set the freeze-drying temperature to -40 - -50 °C, and dry for 24 - 30 h to obtain the modified nano poly(lactic-co-glycolic acid) copolymer and grind it into a powder for standby.

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

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

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

[0065] S22. Adjust the pH value of the nano collagen solution to 8.5 - 9.0 with 0.1 mol / L sodium hydroxide solution. At 0 - 4 °C, slowly add chlorosulfonic acid, continue stirring and reacting for 4 - 6 h, and then adjust the pH value to 7.0 - 7.5 to obtain the third mixed solution;

[0066] S23. Transfer the third mixed solution into a dialysis bag, dialyze it in phosphate buffered saline for 36 - 48 h, change the phosphate buffered saline every 12 h, and obtain the fourth mixed solution after dialysis;

[0067] S24. Slowly drop 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide into the fourth mixed solution for ultrasonic treatment, with an ultrasonic frequency of 40 - 50 kHz. After ultrasonic treatment at room temperature for 0.5 - 1 h, add the growth factor, and continue stirring and reacting at 0 - 4 °C for 24 - 30 h to obtain the fifth mixed solution;

[0068] S25. Transfer the fifth mixed solution into a dialysis bag and dialyze it in phosphate buffered saline at 0 - 4°C for 48 - 52 h, changing the phosphate buffered saline every 12 h. After dialysis, a modified nano - collagen solution is obtained;

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

[0070] The modified nano - collagen is conjugated with a growth factor and has sulfate groups on its surface. Its particle size is 45 - 65 nm, and its specific surface area is 120 - 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 described gynecological vaginal mucosa repair gel, includes the following steps:

[0073] S31. Add purified water into a container, add carbomer into the container and stir evenly. Then, add glycerol, sodium hyaluronate, vitamin E and potassium sorbate in sequence and stir. At the same time, heat in a water bath at a heating temperature of 70 - 80°C until completely dissolved to obtain a sixth mixed solution;

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

[0075] S33. Add purified water and 60 - 80% ethanol again for extraction, twice continuously, to obtain a second extract and a third extract respectively. Mix the extracts and perform vacuum concentration to obtain a Chinese herbal medicine compound extract;

[0076] S34. Under stirring conditions, add tea tree essential oil, albumin, modified nano - collagen and Chinese herbal medicine compound extract into the sixth mixed solution in sequence. After stirring for 0.5 - 1 h, add modified nano - poly (lactic - co - glycolic acid), and continue stirring for 2 - 4 h to obtain a sixth mixed solution;

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

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

[0079] The usage method of the gynecological vaginal mucosa repair gel is as follows: Wash hands, gently insert the gel applicator into the vagina, push the gel applicator, and slowly squeeze the gel into the patient's vagina. Lie supine for 6 - 8 minutes. One treatment course is 7 - 9 days, depending on the degree of injury recovery.

[0080] Example 2: This example discloses a gynecological vaginal mucosa repair gel, which comprises 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 part of potassium sorbate, 0.2 part of modified nano - collagen, 0.2 part of albumin, 0.5 part of tea tree essential oil, 2 parts of aloe vera, 1 part of astragalus membranaceus, 2 parts of dandelion, 1 part of saffron, 1 part of ginseng. The gynecological vaginal mucosa repair gel further comprises a modified nano - poly (lactic - co - glycolic acid) copolymer. The weight - ratio of the modified nano - poly (lactic - co - glycolic acid) copolymer to carbomer is 1:6. The modified nano - poly (lactic - co - glycolic acid) copolymer is obtained by grafting polyacrylic acid on the surface of poly (lactic - co - glycolic acid) and then nano - sizing. The particle size of the modified nano - poly (lactic - co - 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 - poly (lactic - co - glycolic acid) copolymer and the modified nano - collagen in this example are the same as those in Example 1. The preparation method of the gynecological vaginal mucosa repair gel in this example is the same as that in Example 1.

[0081] Example 3: This example discloses a gynecological vaginal mucosa repair gel, which comprises 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 vera, 2 parts of astragalus membranaceus, 3 parts of dandelion, 2 parts of saffron, 2 parts of ginseng. The gynecological vaginal mucosa repair gel further comprises a modified nano - poly (lactic - co - glycolic acid) copolymer. The weight - ratio of the modified nano - poly (lactic - co - glycolic acid) copolymer to carbomer is 1:12. The modified nano - poly (lactic - co - glycolic acid) copolymer is obtained by grafting polyacrylic acid on the surface of poly (lactic - co - glycolic acid) and then nano - sizing. The particle size of the modified nano - poly (lactic - co - 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 - poly (lactic - co - glycolic acid) copolymer and the modified nano - collagen in this example are the same as those in Example 1. The preparation method of the gynecological vaginal mucosa repair gel in this example is the same as that in Example 1.

[0082] Control group 1: The difference between this example and Example 1 is that it does not contain modified nano poly (lactic-co-glycolic acid). This example discloses a gynecological vaginal mucosa repair gel, including 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 membranaceus, 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 example is the same as that in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this example is the same as that in Example 1.

[0083] Control group 2: The difference between this example and Example 1 is that it does not contain modified nano collagen. This example discloses a gynecological vaginal mucosa repair gel, including 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 albumin, 0.8 parts of tea tree essential oil, 3 parts of aloe vera, 1.5 parts of astragalus membranaceus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel further includes a modified nano poly (lactic-co-glycolic acid) copolymer. The weight ratio of the modified nano poly (lactic-co-glycolic acid) copolymer to carbomer is 1:9. The modified nano poly (lactic-co-glycolic acid) copolymer is obtained by grafting polyacrylic acid on the surface of poly (lactic-co-glycolic acid) and then nano-sizing. The particle size of the modified nano poly (lactic-co-glycolic acid) copolymer is 80 - 100 nm, and the specific surface area is 50 - 80 m 2 / g. The preparation method of the modified nano poly (lactic-co-glycolic acid) copolymer in this example is the same as that in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this example is the same as that in Example 1.

[0084] Control group 3: The difference between this example and Example 1 is that it does not contain albumin. This example discloses a gynecological vaginal mucosa repair gel, including 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 membranaceus, 2.5 parts of dandelion, 1.5 parts of saffron, and 1.5 parts of ginseng. The gynecological vaginal mucosa repair gel further includes a modified nano poly (lactic-co-glycolic acid) copolymer. The weight ratio of the modified nano poly (lactic-co-glycolic acid) copolymer to carbomer is 1:9. The modified nano poly (lactic-co-glycolic acid) copolymer is obtained by grafting polyacrylic acid on the surface of poly (lactic-co-glycolic acid) and then nano-sizing. The particle size of the modified nano poly (lactic-co-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-poly(lactic-co-glycolic acid) copolymer and the modified nano-collagen in this example are the same as those in Example 1. The preparation method of a gynecological vaginal mucosa repair gel in this example is the same as that in Example 1.

[0085] Effect evaluation: An animal model of vaginal tissue injury was used to investigate the recovery of the injured area in rats after using the gynecological vaginal mucosa repair gel. Forty-two adult healthy female rats, weighing 200 - 250 g and 8 - 10 weeks old, specific pathogen free, were provided by Hunan Slack Jingda Experimental Animal Company. All experimental rats were adaptively cultured for 7 days under the conditions of temperature (22 ± 2) °C, humidity 50% ± 10%, noise below 85 dB, and a 12 h light-dark cycle, with free access to water and food to ensure their good health status. After 7 days of feeding, the rats were randomly divided into 7 groups, with 6 rats in each group.

[0086] Establishment of the animal model of vaginal tissue injury in rats: Fast the rats for 12 h before treatment. First, anesthetize the rats by injecting 1% sodium pentobarbital. Soak a cotton swab with a diameter of 3 mm in 80% trichloroacetic acid solution and gently insert it into the vagina to a depth of about 2 cm, then gently smear it on the vaginal wall for 10 s, and immediately rinse the vagina 3 times with normal saline. Observe the changes in the vaginal tissue of all rats during the modeling process. If there are symptoms such as redness at the vaginal orifice, local edema, and slight bleeding, it indicates that the modeling is successful. As Figure 3 shown in (a), obvious edema appears in the submucosa of the vaginal tissue of the rats, the tissue space increases, the fibers are separated, inflammatory cell infiltration occurs, and some of the surface epithelial cells fall off, showing obvious symptoms of vaginal tissue injury. 24 h after the modeling is completed, the rats in each experimental group are administered according to the usage method of the gynecological vaginal mucosa repair gel, 2 times a day, about 0.2 g each time, and the administration continues for 9 days, ensuring that other feeding conditions are the same. The blank group is not administered, and 0.9% sodium chloride solution is given according to the above administration method.

[0087] The vaginal tissue pathological changes of rats with vaginal tissue injury were analyzed by the changes in the body weight and total white blood cell count of rats. The specific methods were as follows: Observe and record the body weight of rats in each group before and after treatment; After 9 consecutive days of treatment, on the 10th day, randomly select 2 rats from each experimental group for blood collection from the eyeballs, and use the microscopic counting method to determine the total white blood cell count. After the treatment, randomly select 1 rat from Example 1, anesthetize and sacrifice it, and perform tissue sampling to observe the physiological changes of vaginal tissue cells. The specific methods are as follows: Take the tissue from the vagina to the bifurcation of the uterus of rats in each group, observe the tissue edema, fix the sampled tissue in 4% paraformaldehyde, embed it in paraffin, section it, and perform hematoxylin-eosin staining respectively, and examine the pathological changes of the tissue under the microscope. The changes in the body weight and total white blood cell count of rats in each experimental group before and after treatment are statistically shown in Table 1, and the recovery of the vaginal tissue of rats in each experimental group was observed and recorded visually on the 1st day, 3rd day, 6th day, and 9th day 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 blank group of rats without medication was significantly lower than that of rats in other experimental groups, and the total white blood cell count in the blood was also much higher than that of rats in other experimental groups, indicating that the inflammatory reaction in the rats was severe, resulting in a decrease in the appetite and food intake of the rats. Comparing the body weight and total white blood cell count of rats in the experimental groups of Examples 1-3, it was found that the body weight change of the rats in Example 1 was the largest and the total white blood cell count was the least, indicating that the gynecological vaginal mucosa repair gel prepared from the drug formula of Example 1 had the best effect, and its drug effect was significantly higher than that of other experimental groups. As Figure 3 (b) shows, the epidermal cells and mucosal cells of the vaginal tissue of rats returned to normal arrangement, without abnormal hyperplasia or infiltration of inflammatory cells, and the structures such as the muscle layer, epithelial layer, and submucosal layer of the vaginal wall were intact without damage marks. Comparing the body weight and total white blood cell count of rats in Example 1 with those in the experimental groups of Control Groups 1-3, it was found that when the three drugs, namely modified nano-poly (lactic-co-glycolic acid), albumin, and modified nano-collagen, existed simultaneously in the gynecological vaginal mucosa repair gel, the drug effect of the gynecological vaginal mucosa repair gel was better, indicating that there was a synergistic effect among the three substances, namely modified nano-poly (lactic-co-glycolic acid), albumin, and modified nano-collagen, in the gynecological vaginal mucosa repair gel.

[0091] According to the symptoms shown by the recovery of rats with vaginal tissue injury models, they were divided into 5 levels, namely not relieved (A), slightly relieved (B), moderately relieved (C), almost cured (D), and completely cured (E), and the specific manifestations were as follows:

[0092] Non - remission (A): There was no obvious improvement in vaginal tissue injury. The vaginal mucosal epithelium showed degeneration and necrosis, with extremely thin thickness. A large number of inflammatory cells were infiltrated under the mucosa. The vaginal secretions were abnormal, showing thin, light yellow or purulent and bloody, etc. The rats showed symptoms such as vulvar burning discomfort, itching pain, and vaginal dryness.

[0093] Mild remission (B): The vaginal tissue injury began to be alleviated, but the improvement was not obvious. The thickness of the vaginal mucosal epithelium increased to some extent, but was still relatively thin. The inflammatory cell infiltration under the mucosa decreased. The vaginal secretions were still somewhat abnormal to a certain degree, but improved compared to before. The vaginal discomfort symptoms of the rats were alleviated, but still detectable.

[0094] Moderate remission (C): The vaginal tissue injury was significantly alleviated. The thickness of the vaginal mucosal epithelium was close to normal. The inflammatory cell infiltration under the mucosa was significantly reduced. The vaginal secretions basically returned to normal, without obvious abnormalities. The vaginal discomfort symptoms of the rats basically disappeared.

[0095] Nearly cured (D): The vaginal tissue injury was significantly restored, approaching the normal state. The structure of the vaginal mucosal epithelium was complete, with normal thickness. There was no inflammatory cell infiltration under the mucosa. The vaginal secretions were completely normal, without abnormal manifestations. The vaginal function of the rats basically returned to normal, without discomfort symptoms.

[0096] Completely cured (E): The vaginal tissue injury was completely restored, indistinguishable from normal rats. The structure, thickness, and function of the vaginal mucosal epithelium all returned to normal. Physiological indicators such as vaginal secretions and pH values were within the normal range. The vaginal function of the rats was completely restored, without any discomfort symptoms.

[0097] Table 2 Statistical results of the 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 CDCDCD 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 shows the statistical results of the recovery of rats with vaginal tissue injury model in each experimental group. It can be seen from Table 2 that there was almost no obvious improvement in the vaginal tissue injury of the blank group rats without medication. When the gynecological vaginal mucosal repair gel prepared in Example 1 was used on the injured parts of the rats, the recovery of the rats was the best. From the 3rd day, the 6th day to the end of the 9 - day treatment course, the recovery of the rats was better than that of other experimental groups, showing excellent drug efficacy. By comparing Examples 1 - 3 with Control Groups 1 - 3, it can be found that the recovery of the rats in Examples 1 - 3 was also significantly better than that in Control Groups 1 - 3. This indicates that by adding three substances, namely modified nano - poly (lactic - co - glycolic acid), albumin, and modified nano - collagen, simultaneously during the gel production process, a gynecological vaginal mucosal repair gel with excellent repair performance can be obtained.

[0100] After the above limited experiments, the application effect of a gynecological vaginal mucosa repair gel in Embodiment 1 of the present invention is remarkable. By adding three substances, namely modified nano-poly(lactic-co-glycolic acid), albumin, and modified nano-collagen, 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 change of the physiological environment, the bioavailability of the drug is improved, the inflammatory reaction is reduced, an immune microenvironment conducive to tissue repair is created, and the cell tissue repair and regeneration process is accelerated, enabling the vaginal tissue to quickly recover to the normal level.

[0101] Finally, it should be noted that although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within 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; 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. The solid is precooled at -60 to -80°C for 2 to 4 hours, and the freeze-drying temperature is set to -40 to -50°C. After drying for 24 to 30 hours, the modified nano-polylactic acid-glycolic acid copolymer is obtained and ground into powder for standby use; 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. The modified nano-collagen solution is freeze-dried at a drying temperature of -40 to -60°C for 12 to 18 hours to obtain the modified nano-collagen and ground into powder for later use; 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; The preparation method of the gynecological vaginal mucosa repair gel 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.

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

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

4. The gynecological vaginal mucosa repair gel according to claim 1, 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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