Private care thixotropic gel and preparation method thereof

Abstract

The invention relates to private care thixotropic gel and a preparation method thereof, and belongs to the technical field of gel. The gel is prepared from 0.01 wt%-5 wt% of aloe-mushroom repairing gel, 0.01 wt%-15 wt% of chamomile essence, 0.5 wt%-1.8 wt% of PCO ternary preservative, 0.05 wt%-5 wt% of lactic acid solution, 0.01 wt%-8 wt% of allantoin, 1 wt%-5 wt% of quaternized chitosan, 0.5 wt%-2.5 wt% of tannic acid and 0.01 wt%-10 wt% of sodium alginate-chitosan probiotic microcapsules, probiotic extract composite liquid serves as a core material, and sodium alginate and chitosan serve as wall materials. The composition comprises the following components in percentage by weight: 0.01 to 10 percent of polysorbate-80, 0.01 to 50 percent of caprylic / capric triglyceride and the balance of water. The private care thixotropic gel with a yield stress point can be formed at a relatively low concentration, when the gel is applied to private parts, the gel is easy to apply in a semi-solid state, the mucous membrane adhesion is improved, and the vagina retention time is prolonged.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of gels, and more particularly relates to a private care thixotropic gel and a preparation method thereof. BACKGROUND

[0002] The vaginal wall of the vagina is composed of three layers from inside to outside, namely mucosa, muscle layer and adventitia. Among them, the mucosa refers to the covering epithelium inside the vagina, and this layer of membrane mainly plays a protective role. There are reproductive tract immune cells under the vaginal mucosa, which are always on the move, identify and eliminate pathogens, and can effectively prevent bacteria, fungi and other microorganisms from invading the body. Moreover, the vaginal mucosa can keep the vagina in a weakly acidic environment, which can play a role in killing bacteria.

[0003] However, due to dietary habits, poor hygiene and cleaning, or external damage, the female vagina is prone to infection, resulting in an increase in harmful bacteria, inflammation, disruption of the vaginal acid-base balance, and further triggering abnormal leukorrhea, vaginitis and other gynecological diseases. The bacteriostatic repair ability of the vaginal mucosa itself is limited, so external repair is needed to help inhibit harmful bacteria at this time.

[0004] To solve the health problems of the female vaginal area, a variety of private care products can be purchased on the market, but most of these private care products use chemical components to synthesize, and the components can cause strong irritation to the vaginal mucosa, thereby disrupting the balance of vaginal flora, especially disrupting the weakly acidic environment maintained by lactobacilli, and thus making gynecological inflammation problems prone to recur.

[0005] Private care vaginal products should be weakly acidic, and the upper limit of their osmotic pressure should not exceed 1200 mOsm / kg, in order to minimize the risk of mucosa / epithelial damage. In terms of permeability, although low-osmotic vaginal products can temporarily enhance the permeability of the mucosa, they can cause excessive water absorption of epithelial cells, leading to a fragile barrier; and high-osmotic vaginal products can suck water from the cells, leading to mucosal atrophy, interference or shedding, affecting the health of the vaginal tissue. Therefore, it is necessary to develop a gel product suitable for external use in the vagina. SUMMARY

[0006] The present application aims to provide a private care thixotropic gel and a preparation method thereof. The prepared gel helps to maintain the vaginal microecological balance, improve the cleanliness of the vagina, and improve the immunity of the vaginal mucosa.

[0007] The purpose of the present application can be achieved by the following technical solutions: A private care thixotropic gel, comprising the following components in mass percentage: 0.01-5wt% aloe-mushroom repair jelly, comprising aloe vera leaf juice, sodium alginate, tricholoma populinum extract, ganoderma lucidum extract, lentinula edodes extract, and inonotus obliquus extract; 0.01-15wt% Chamomile essence, including chamomile flower / leaf extract and water; 0.5-1.8wt% PCO ternary preservative, including phenoxyethanol, octoxyglycerin and benzoic acid; 0.05-5wt% lactic acid solution, including lactic acid and water; 0.01-8wt% allantoin; 1-5wt% quaternary ammonium chitosan; 0.5-2.5wt% tannic acid; 0.01-10wt% sodium alginate-chitosan probiotic microcapsule, with probiotic extract composite liquid as core material, sodium alginate and chitosan as wall material; the probiotic extract composite liquid includes water, caprylic / capric triglyceride, polyglyceryl-3 diisostearate, polyglyceryl-2 dipolyhydroxystearate, lactic acid bacteria fermentation extract, lactobacillus fermentation product, fermentation extract of single spore bacteria, fermentation product extract of schizosaccharomyces pombe, yeast fermentation product, larch mushroom extract, red ganoderma extract, lentinus edodes extract, sodium alginate, birch inonotus extract, chondrus crispus, citric acid, chitosan; 0.01-10wt% polysorbate-80; 0.01-50wt% caprylic / capric triglyceride and the rest water.

[0008] Further, the mass ratio of the quaternary ammonium chitosan and tannic acid is 1-3:1.

[0009] Further, the wall-core ratio of the sodium alginate-chitosan probiotic microcapsule is 1:3-4; the particle size of the sodium alginate-chitosan probiotic microcapsule is 30-50 microns.

[0010] Further, the molecular weight of sodium alginate in the wall material of the sodium alginate-chitosan probiotic microcapsule is 10-200kDa, the molecular weight of chitosan is 50-100kDa, and the degree of deacetylation of chitosan is ≥85%.

[0011] Sodium alginate is a natural anionic polysaccharide, and chitosan is a cationic polymer obtained by deacetylation of chitin. Its pH response characteristics make its amino groups protonate in an acidic environment, forming an electrostatic complex with the carboxyl groups of sodium alginate, thereby enhancing the stability and adhesion of the microcapsule.

[0012] Further, the preparation method of the sodium alginate-chitosan probiotic microcapsule is: A1, dissolve sodium alginate powder in deionized water, heat in water bath at 60-80℃ overnight, then cool to room temperature, get 1.5-2.5wt% sodium alginate solution; A2, the sodium alginate solution is mixed with the probiotic extract solution at a wall-to-core ratio of 1:3-4, and a mixed solution is obtained by homogenization; A3, the mixed solution is dropped into a CaCl2 solidification solution with a concentration of 3-5%, stirred at a speed of 400-600 r / min, and then solidified to obtain calcium alginate gel microspheres; A4, after washing the calcium alginate microspheres, immerse them in a chitosan solution with a concentration of 0.75-1.0% and a pH of 4.5-5.0, continue to stir, wash with water, and obtain wet capsules; finally, vacuum freeze-drying is performed to obtain sodium alginate-chitosan probiotic microcapsules.

[0013] Further, in step A3, the dropping speed of the mixed solution is 25-35 drops / min; and the solidification temperature is 40-50°C.

[0014] Further, in step A4, the temperature for vacuum freeze-drying is -15 to -25°C; the vacuum pressure is 500-500 Pa; and the drying time is 16-20 hours.

[0015] Further, the mass fraction of lactic acid in the lactic acid solution is 85.0-95.0%, and the balance is water.

[0016] Further, the mass fraction of aloe vera leaf juice in the aloe-mushroom repair jelly is 90-98%; The mass fraction of sodium alginate in the aloe-mushroom repair jelly is 1-5%; The mass fraction of the P. djamor extract in the aloe-mushroom repair jelly is 0.1-5%; The mass fraction of the Ganoderma lucidum extract in the aloe-mushroom repair jelly is 0.0001-5%; The mass fraction of the Lentinula edodes extract in the aloe-mushroom repair jelly is 0.0001-5%; The mass fraction of the Inonotus obliquus extract in the aloe-mushroom repair jelly is 0.0001-5%.

[0017] Further, the mass fraction of the chamomile flower / leaf extract in the chamomile essence is 0.001-45%, and the balance is water.

[0018] Further preferably, the mass fraction of the chamomile flower / leaf extract in the chamomile essence is 5-35%, and the balance is water.

[0019] Further, the mass fraction of phenoxyethanol in the PCO ternary preservative is 54.0-56.0%; The mass fraction of octisalate in the PCO ternary preservative is 34.0-36.0%; The mass percentage of the benzoic acid in the PCO ternary preservative is 9.0-11.0%.

[0020] Further, the mass percentage of the lactic acid in the lactic acid solution is 85.0-95.0%, and the balance is water.

[0021] Further, the mass percentage of water in the probiotic extract composite solution is 15-30%. The mass percentage of caprylic / capric triglyceride in the probiotic extract composite solution is 40-55%. The mass percentage of polyglyceryl-3 diisostearate in the probiotic extract composite solution is 1-5%. The mass percentage of polyglyceryl-2 dipolyhydroxystearate in the probiotic extract composite solution is 1-10%. The mass percentage of lactic acid bacteria fermentation extract in the probiotic extract composite solution is 0.0001-10%. The mass percentage of lactobacillus fermentation product in the probiotic extract composite solution is 0.0001-10%. The mass percentage of fermentation product extract of Streptomyces sp. in the probiotic extract composite solution is 0.0001-10%. The mass percentage of fermentation product extract of Schizosaccharomyces pombe in the probiotic extract composite solution is 0.0001-10%. The mass percentage of fermentation product of Saccharomycete in the probiotic extract composite solution is 0.0001-10%. The mass percentage of extract of Lactarius deliciosus in the probiotic extract composite solution is 0.0001-5%. The mass percentage of extract of Ganoderma lucidum in the probiotic extract composite solution is 0.0001-5%. The mass percentage of extract of Lentinula edodes in the probiotic extract composite solution is 0.0001-5%. The mass percentage of sodium alginate in the probiotic extract composite solution is 0.0001-5%. The mass percentage of extract of Inonotus obliquus in the probiotic extract composite solution is 0.0001-5%. The mass percentage of Chondrus crispus in the probiotic extract composite solution is 0.0001-5%. The mass percentage of citric acid in the probiotic extract composite solution is 0.0001-2%. The mass percentage of chitosan in the probiotic extract composite solution is 0.0001-5%.

[0022] Further, the mass percentage of the aloe-mushroom repair gel is 1-5wt%, preferably 2-5wt%, and specifically can be 2wt%, 3wt%, 4wt% or 5wt%.

[0023] Further, the mass percentage of the chamomile essence is 1-15wt%, preferably 3-10wt%, and specifically can be 3wt%, 4wt%, 5wt%, 6wt%, 7wt%, 8wt%, 9wt% or 10wt%.

[0024] Further, the mass percentage of the PCO ternary preservative is 0.8-1.5wt%, and specifically can be 0.8wt%, 0.9wt%, 1wt%, 1.1wt%, 1.2wt%, 1.3wt%, 1.4wt% or 1.5wt%.

[0025] Further, the mass percentage of the lactic acid solution is 0.5-5wt%, preferably 1-4wt%.

[0026] Further, the mass percentage of the allantoin is 0.5-8wt%, preferably 0.5-6wt%, and specifically can be 0.5wt%, 1wt%, 2wt%, 3wt%, 4wt%, 5wt% or 6wt%.

[0027] Further, the mass percentage of the quaternized chitosan is 1-3wt%.

[0028] Further, the mass percentage of the tannic acid is 0.5-1.5wt%.

[0029] Further, the mass percentage of the sodium alginate-chitosan probiotic microcapsule is 1-10wt%, preferably 2-10wt%, and specifically can be 2wt%, 3wt%, 4wt%, 5wt%, 6wt%, 7wt%, 8wt%, 9wt% or 10wt%.

[0030] Further, the mass percentage of the polysorbate-80 is 1-10wt%, preferably 2-8wt%, and specifically can be 2wt%, 3wt%, 4wt%, 5wt%, 6wt%, 7wt% or 8wt%.

[0031] Further, the mass percentage of the caprylic / capric triglyceride is 1-50wt%, and preferably can be 1-10wt%, 10-20wt%, 20-30wt%, 30-40wt%, and specifically can be 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt%, 16wt%, 17wt%, 18wt%, 19wt%, 20wt%, 21wt%, 22wt%, 23wt%, 24wt% or 25wt%.

[0032] The preparation method of the private care thixotropic gel comprises the following steps: Step one, heat the deionized water to 85-90℃, keep 75-85℃; and heat the polysorbate-80 to 55-65℃; Step two, disperse aloe-mushroom repair jelly in deionized water; Step three, when the product of step two is cooled to 30-40℃, add quaternary ammonium chitosan, tannic acid, PCO ternary preservative and allantoin in sequence with stirring operation, to obtain an aqueous phase; Step four, premix chamomile essence and caprylic / capric triglyceride, then add heated polysorbate-80, mix and stir to obtain an oil phase; Step five, continuously add the oil phase of step four into the aqueous phase of step three with stirring operation, then add sodium alginate-chitosan probiotic microcapsules, and finally add lactic acid solution as a pH regulator to adjust the pH value of the system to 3.8-5 to obtain the final product.

[0033] Further, the pH value of the system is 3.8-4.5.

[0034] In the technical solution, quaternary ammonium chitosan (QCS) is a derivative obtained by quaternary ammonium modification of chitosan, which has good water solubility and biocompatibility. Tannic acid (TA) is a natural polymer rich in polyphenols, which can form hydrogen bond and coordination bond network with QCS. In the vaginal environment, the amino groups on the molecular chain of QCS are protonated, enhancing the interaction with TA and forming a stable thixotropic gel network. This network will temporarily dissociate when subjected to shear force, reducing the viscosity and exhibiting liquid properties; when the shear force disappears, the network gradually recovers, the viscosity rises, and a solid structure is reformed, thus realizing thixotropy. This property enables the gel to adapt to the dynamic environment of the vagina, maintaining adhesion while slowly releasing active ingredients to achieve the desired therapeutic effect.

[0035] Aloe-mushroom repair jelly is a fully natural dry mixture composed of sodium alginate, aloe vera leaf juice and four kinds of mushroom extract, which helps to soothe and repair damaged skin, while forming a protective barrier to help maintain moisture and promote healing; in addition, aloe-mushroom repair jelly is a very unique rheological modifier that can impart unique tactile and suspension properties to the gel.

[0036] Chamomile essence has anti-inflammatory, antibacterial, soothing, mucosal sedative and antioxidant effects. On the one hand, chamomile essence can impart a certain fragrance and soothing effect to the gel; on the other hand, due to its liposolubility, chamomile ingredients diffuse slowly in the hydrogel, which can play a natural slow-release role.

[0037] PCO ternary preservative is a composite preservative, which has broad-spectrum antibacterial effect and can inhibit the growth of bacteria, fungi and microorganisms. The preservative itself is mostly a small-molecule organic compound, which can be distributed into the gel matrix and vaginal secretions, and quickly released to play an antibacterial role. However, under the action of the gel matrix, the release rate of the preservative is still slower than that of the pure solution, thereby maintaining a long-term antibacterial concentration in the vagina.

[0038] The lactic acid solution is used to adjust the pH of the vaginal gel to weak acidity, so as to maintain the vaginal microecological balance and play a certain antibacterial and skin renewal promoting effect.

[0039] Allantoin is a skin conditioner, which has the effects of moisturizing, soothing, promoting wound healing and anti-inflammatory. At the same time, the presence of allantoin can reduce the mucous membrane irritation caused by other ingredients, so that the gel can play a long-acting effect more comfortably in the vagina.

[0040] The core material of the sodium alginate-chitosan probiotic microcapsule, i.e. the probiotic extract composite liquid, contains lactobacillus and other symbiotic species, which can regulate the balance of vaginal flora, inhibit the growth of harmful bacteria, and then promote and maintain the normal and healthy skin microbiota. By microencapsulating the probiotics and then dispersing them in the gel, the probiotics are adhered to the mucosal surface and release live bacteria to colonize the vaginal mucosa, preventing the probiotics from being released too quickly and inactivated. This design realizes the slow and sustained release of probiotics, prolonging the action time.

[0041] Polysorbate-80 (Tween 80) is a non-ionic surfactant with emulsifying and solubilizing effects, which helps the oil components such as chamomile essence and caprylic / capric triglyceride to be uniformly dispersed in the hydrogel, forming a stable emulsion system. In terms of sustained release, Tween 80 can increase the solubility of certain active substances, so that they are more dissolved in the water phase, thereby accelerating the release.

[0042] Caprylic / capric triglyceride is a medium-chain fatty acid triglyceride (MCT oil), which, in the gel, can dissolve and carry fat-soluble active ingredients as an oil phase, forming an oil-in-water emulsion. The presence of the oil phase can delay the release of the active ingredients to some extent, and increase the lubricity and application feeling of the gel, making the product more comfortable to use.

[0043] The above components synergistically improve the vaginal environment and improve the vaginal mucosal immunity, and have the effects of lubrication, soothing, moisturizing, anti-inflammatory and promoting tissue repair.

[0044] The beneficial effects of the present application are: (1) The gel of the present application realizes thixotropy in the vaginal environment through the three-dimensional network structure formed by quaternary ammonium chitosan and tannic acid, and realizes semi-solid state under static, which is convenient for coating and adhering to the surface of the vaginal mucosa during use, realizes "semi-solid" residence, thereby prolonging the contact time of the active ingredients and the mucosa; gradually undergoes "thixotropic" liquefaction under mechanical shearing, changes back to liquid state and penetrates into the mucosa, so that the active ingredients therein can be continuously absorbed and permeated, and long-acting care effect is achieved. This solid-liquid characteristic makes the gel have good adhesion and retention performance, and also ensures that the active ingredients are fully permeated, so as to achieve the comprehensive care effect of maintaining the vaginal microecological balance, improving the cleanliness and improving the mucosal immunity.

[0045] (2) The present application can form a private care thixotropic gel with a yield stress point at a relatively low concentration, which is easy to apply in semi-solid state when applied to the private part, improves the mucosal adhesion, and increases the vaginal residence time; when changing from semi-solid state to liquid state, the internal physical crosslinking is opened, the active ingredients penetrate into the mucosa, and have a slow-release property, which improves the utilization rate of the active ingredients; and the active ingredients are combined with aloe-mushroom repair jelly, probiotic extract composite liquid and chamomile essence, realizing multiple synergistic effects, which can effectively maintain the vaginal microecological balance, improve the cleanliness of the vagina and improve the mucosal immunity of the vagina. DETAILED DESCRIPTION

[0046] In order to further illustrate the technical means and effects adopted by the present application to achieve the predetermined invention purpose, the specific embodiments, structures, features and effects according to the present application are described in detail as follows in combination with examples.

[0047] The raw material procurement information used in all examples and comparative examples of the present application is as follows: The aloe-mushroom repair jelly, chamomile essence and probiotic extract composite liquid are all purchased from LCOSMETIX LIMITED, and the batch number of the aloe-mushroom repair jelly is LCosmetix HealJelly-Advance; the batch number of the chamomile essence is LCosmetix ProGuard-Chamomile; and the batch number of the probiotic extract composite liquid is LCosmetix Capsucare-Probio.

[0048] PCO ternary preservative is purchased from PCI INNOVATIVE CHEMICALS SDN. BHD. Lactic acid is purchased from KOBION TRADING (SHANGHAI) CO., LTD.

[0049] Allantoin is purchased from ASHLAND (CHINA) INVESTMENT CO., LTD.

[0050] Polysorbate-80 is purchased from Guangdong Runhua Chemical Co., Ltd.

[0051] Caprylic / capric triglyceride, purchased from Wuxing Chemical Industry Co., Ltd.

[0052] Example 1 A private care thixotropic gel, comprising the following components by mass percentage: 3wt% aloe-mushroom repair jelly; 5wt% chamomile essence, wherein the concentration of chamomile flower / leaf extract is 10%; 1wt% PCO ternary preservative, wherein the mass percentage of phenoxyethanol, octoxyglycerol and benzoic acid in the PCO ternary preservative is 55%, 35% and 10% respectively; 0.05-5wt% lactic acid solution, wherein the mass percentage of lactic acid in the lactic acid solution is 90%; 0.6wt% allantoin; 2wt% quaternary ammonium chitosan; 1wt% tannic acid; 10wt% sodium alginate-chitosan probiotic microcapsules, with probiotic extract composite liquid as core material, sodium alginate and chitosan as wall material; the wall-core ratio is 1:3.5; 5wt% polysorbate-80; 10wt% caprylic / capric triglyceride and the balance of water.

[0053] The preparation method of the above-mentioned sodium alginate-chitosan probiotic microcapsules is as follows: A1, dissolve sodium alginate powder in deionized water, heat in water bath at 70℃ overnight, then cool to room temperature, obtain a 2wt% sodium alginate solution; A2, mix the sodium alginate solution with the probiotic extract composite liquid according to the wall-core ratio of 1:3.5, homogenize for 5 minutes, obtain a mixed solution; A3, use a 100 microliter syringe to drop the mixed solution into a 4% CaCl2 solidification solution, control the dropping speed at 30 drops per minute, stir at a speed of 500r / min, then solidify, obtain calcium alginate gel microspheres; A4, rinse the calcium alginate microspheres with distilled water for 3 times to remove the surface residual Ca 2＋ and free probiotics, then immerse in a chitosan solution with a concentration of 0.75-1.0% and pH adjusted to 4.5-5.0 with 1% acetic acid, continue to stir for 30 minutes, so that the chitosan molecules combine with the outer layer of sodium alginate through electrostatic interaction to form a stable chitosan-sodium alginate composite film, then wash with distilled water to remove the surface residual chitosan and acetic acid, obtain wet capsules; finally, vacuum freeze-drying at a pre-freezing temperature of-20℃ and a vacuum pressure of 600Pa for 18 hours, obtain sodium alginate-chitosan probiotic microcapsules.

[0054] The preparation method of the private care thixotropic gel is as follows: Step one, heat the deionized water to 85°C, and keep the temperature at 80±2°C; and heat the polysorbate-80 to 60°C; Add the aloe-mushroom repair jelly and mix, disperse and homogenize; Step two, disperse the aloe-mushroom repair jelly in the deionized water, and stir until completely dissolved; Step three, when the product of step two is cooled to 35°C, sequentially add the quaternary ammonium chitosan, tannic acid, PCO three-way preservative and allantoin to the water phase while stirring; Step four, premix the chamomile essence and caprylic / capric triglyceride, then add the heated polysorbate-80 and stir until uniform to obtain the oil phase; Step five, continuously and slowly add the oil phase of step four to the water phase of step three while stirring, then add the sodium alginate-chitosan probiotic microcapsule and mix again; Step six, add the lactic acid solution as a pH adjuster to adjust the pH value of the system to 3.8-5 to obtain the final product; Step seven, irradiate the final product under the condition of 8kGy for sterilization, then fill it into a sterile syringe, seal and package to obtain the final product.

[0055] Example 2 A private care thixotropic gel, comprising the following components by mass percentage: 5wt% aloe-mushroom repair jelly; 3wt% chamomile essence, wherein the concentration of chamomile flower / leaf extract is 10%; 1.5wt% PCO three-way preservative, wherein the proportions of phenoxyethanol, octisalate and benzoic acid in the PCO three-way preservative are 55%, 35% and 10% respectively; 0.05-5wt% lactic acid solution, wherein the mass proportion of lactic acid in the lactic acid solution is 90%; 1wt% allantoin; 3wt% quaternary ammonium chitosan; 1wt% tannic acid; 5wt% sodium alginate-chitosan probiotic microcapsule, wherein the probiotic extract composite liquid is used as the core material, and sodium alginate and chitosan are used as the wall material; the wall-to-core ratio is 1:3.5; 3wt% polysorbate-80; 12wt% caprylic / capric triglyceride and the balance of water.

[0056] The preparation method is the same as that of Example 1.

[0057] Example 3 A private care thixotropic gel comprising the following components by mass percentage: 2 wt% aloe-mushroom repair jelly; 10 wt% chamomile essence, wherein the concentration of chamomile flower / leaf extract is 10%; 0.8 wt% PCO ternary preservative, wherein the proportions of phenoxyethanol, octoxyglycerin and benzoic acid in the PCO ternary preservative are 55%, 35% and 10%, respectively; 0.05-5 wt% lactic acid solution, wherein the mass proportion of lactic acid in the lactic acid solution is 90%; 5 wt% allantoin; 1 wt% quaternized chitosan; 0.5 wt% tannic acid; 2 wt% sodium alginate-chitosan probiotic microcapsule, wherein the probiotic extract composite liquid is used as the core material, sodium alginate and chitosan are used as the wall material, and the wall-to-core ratio is 1:3.5; 8 wt% polysorbate-80; 5 wt% caprylic / capric triglyceride and the balance of water.

[0058] The preparation method is the same as that of Example 1.

[0059] Comparative Example 1 The difference between this comparative example and Example 1 is that allantoin is replaced by sodium hyaluronate in this comparative example. The other components and preparation method are the same as those of Example 1.

[0060] Comparative Example 2 The difference between this comparative example and Example 1 is that the addition amounts of quaternized chitosan and tannic acid in this comparative example are 0. The other components and preparation method are the same as those of Example 1.

[0061] Comparative Example 3 The difference between this comparative example and Example 1 is that the sodium alginate-chitosan probiotic microcapsule is replaced by a single probiotic extract composite liquid in this comparative example. The other components and preparation method are the same as those of Example 1.

[0062] Comparative Example 4 The difference between this comparative example and Example 1 is that caprylic / capric triglyceride is replaced by cetyl alcohol stearate in this comparative example. The other components and preparation method are the same as those of Example 1.

[0063] The samples prepared in Examples 1-3 and Comparative Examples 1-4 are subjected to the following performance tests: (1) Physical property test Rheological property test: The yield stress and thixotropic ring area were measured by MCR300 rheometer at 37℃ to simulate the vaginal temperature, to evaluate the thixotropy of the gel.

[0064] Adhesion test: The adhesion of the gel on the glass plate was measured by a rotational viscometer to simulate its adhesion ability on the vaginal mucosa.

[0065] Thixotropic transition time test: The complete transition time from solid to liquid was recorded by observing the morphological changes of the gel in simulated vaginal fluid (SVF).

[0066] The formula of the simulated vaginal fluid is as follows: NaCl 3.51 g / L; KOH 1.4 g / L; Ca(OH)2 0.222 g / L; bovine serum albumin 18 mg / L; lactic acid 2.0 g / L; glycerol 160 mg / L; urea 0.4 g / L; glacial acetic acid 1.0 g / L; glucose 5.0 g / L; water to 1 L; and 0.1N HCl to adjust the pH to 4.2±0.1.

[0067] pH stability test: After the sample was placed at room temperature for 72 hours, 1.0 g of the gel sample was weighed, 9.0 mL of purified water was added, and the sample was fully stirred and dissolved. Then, the electrode of a precision pH meter was immersed in the solution, and the pH value was recorded after the reading was stable. The determination was repeated for three times, and the average value was taken.

[0068] The performance test results are shown in Table 1.

[0069] (2) Biological activity test Probiotic survival rate test: The gel sample was incubated in SVF at 37℃ to simulate the vaginal environment, and samples were taken at 0, 24, 48 and 72 hours, respectively, to determine the number of viable bacteria. The protective effect of the microcapsule on the probiotics was evaluated.

[0070] Anti-inflammatory activity test: The inhibition rate of the gel on inflammatory factors such as TNF-α and IL-6 was determined by ELISA method.

[0071] Antioxidant activity test: The antioxidant capacity of the gel was evaluated by DPPH free radical scavenging method.

[0072] The test results are shown in Table 2.

[0073] (3) Therapeutic effect test 70 female volunteers aged 18-45 years diagnosed as bacterial vaginosis (BV) according to the Amsel standard were selected for a 1-week trial, and followed up for 30 days. Each group had 10 volunteers, corresponding to the samples of Examples 1-3 and Comparative Examples 1-4, respectively. The volunteers used the syringe to send about 5 g of the gel of the present application into the deep part of the vagina after cleaning the vulva every night, and used it continuously for 7 days. No other vaginal care products were used during the trial period.

[0074] Observation period: ①Baseline period (day 0): Record demographic data, medical history, gynecological examination, and collect vaginal secretions for laboratory testing.

[0075] ②Treatment period (days 1-7): Record daily symptom diary (itching, burning, secretions).

[0076] ③Follow-up period: Follow-up at 3 days after stopping medication (day 10), 7 days (day 14), 14 days (day 21), and 21 days (day 30).

[0077] Primary efficacy endpoint and evaluation method: ①Refer to the "Clinical Application Expert Consensus on Vaginal Microecology Evaluation", use standardized scoring system, and perform Vaginal Microecology Evaluation System (VMES) scoring.

[0078] Scoring criteria: Normal (0 points): Bacterial density Ⅱ-Ⅲ, diversity Ⅰ-Ⅱ, lactobacillus as dominant bacteria, pH ≤4.5, white blood cells <5 / HP, negative for clue cells, positive for H2O2.

[0079] Mild imbalance (1 point): 4-5 items meet the normal criteria.

[0080] Moderate imbalance (2 points): 2-3 items meet the normal criteria.

[0081] Severe imbalance (3 points): 0-1 item meets the normal criteria, or positive for clue cells.

[0082] Endpoint: The proportion of subjects with VMES score improvement ≥2 points at 7 days after stopping medication (day 14) compared to baseline (improvement rate).

[0083] ②Diagnose BV using the classic Amsel criteria, 1 point for each item, and total score ≥3 points for BV.

[0084] The four criteria are: homogeneous, thin, gray vaginal discharge. Vaginal discharge pH >4.5. Positive amine test (fishy smell of secretions with 10% KOH). Clue cells >20% under high power.

[0085] Endpoint: The proportion of subjects with Amsel standard total score reduced to 0-1 points at 7 days after stopping medication (clinical cure rate).

[0086] ③Symptom relief rate: Record the severity of symptoms recorded daily by subjects (0-3 points), including, Itching: 0=no, 1=mild, 2=moderate, 3=severe.

[0087] Burning pain: 0 = none, 1 = mild, 2 = moderate, 3 = severe.

[0088] Discharge: 0 = normal, 1 = mild increase, 2 = moderate increase, 3 = severe increase.

[0089] Endpoint: proportion of subjects with a 50% reduction in total symptom score at day 3 (day 10) post-treatment from baseline.

[0090] (4) Patient satisfaction: at the final follow-up, subjects filled in a satisfaction questionnaire (Likert 5-point scale). Among them, 1 = very dissatisfied, 2 = dissatisfied, 3 = average, 4 = satisfied, 5 = very satisfied.

[0091] Endpoint: proportion of subjects with a satisfaction score of ≥4.

[0092] The performance test results are shown in Table 3.

[0093] Table 1 From the test results in Table 1, it can be seen that compared with Comparative Examples 1-4, the physical property test results of Examples 1-3 and Comparative Example 3 are better, meeting the adhesion requirements in the vaginal environment (800-1800 Pa), among which, the physical property results of Comparative Example 2 are the worst, indicating that the addition of quaternary ammonium chitosan and tannic acid plays a very important role in the stability of the gel structure. The yield stress of Example 4 is 700 Pa, indicating that caprylic / capric triglyceride has a unique advantage in maintaining the gel structure.

[0094] Table 2 From the test results in Table 2, it can be seen that compared with Comparative Examples 1-4, the survival rate of probiotics, TNF-α inhibition rate, IL-6 inhibition rate and DPPH clearance rate of Examples 1-3 after 72 hours of exposure in the simulated vaginal environment are significantly higher than those of the comparative examples, indicating that the microcapsule technology is crucial for protecting the activity of probiotics in an acidic environment, and the thixotropic network formed by quaternary ammonium chitosan and tannic acid and caprylic / capric triglyceride have a positive effect on the protection of probiotic activity, anti-inflammatory activity and antioxidant activity.

[0095] Table 3 From the test results in Table 3, it can be seen that after using the samples of Examples 1-3, Examples 1-3 are superior to Comparative Examples in improving vaginal microecology, relieving symptoms, reducing recurrence rate and improving patient satisfaction. From the results in Table 3, it can be seen that the gel of the technical solution has the effects of maintaining the balance of vaginal microecology, improving vaginal cleanliness and improving the immunity of vaginal mucosa.

[0096] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application in any form. Although the present application has been described above with reference to preferred embodiments, the present application is not intended to be limited to the above-described embodiments, and any person skilled in the art, without departing from the technical scope of the present application, can make some changes or modifications to the above-described embodiments, or make equivalent embodiments with equivalent changes, as long as the changes or modifications do not depart from the technical scope of the present application. Any modification, change, or equivalent change made to the above-described embodiments, based on the technical essence of the present application, still falls within the scope of the present application.

Claims

1. A feminine care thixotropic gel, characterized in that: By mass percentage, it includes the following components: 0.01-5wt% Aloe-Mushroom Repair Gel, including Aloe vera leaf juice, sodium alginate, mushroom extract, Ganoderma lucidum extract, shiitake mushroom extract, and Inonotus obliquus extract; 0.01-15wt% chamomile extract, including chamomile flower / leaf extract and water; 0.5-1.8wt% PCO ternary preservative, including phenoxyethanol, octyl glycol and benzoic acid; 0.05-5wt% lactic acid solution, containing lactic acid and water; 0.01-8wt% allantoin; 1-5wt% quaternized chitosan; 0.5-2.5wt% tannic acid; 0.01-10wt% sodium alginate-chitosan probiotic microcapsules, with a probiotic extract complex as the core material and sodium alginate and chitosan as the wall material; the probiotic extract complex includes water, caprylic / capric triglyceride, polyglycerol-3 diisostearate, polyglycerol-2 dihydroxystearate, lactic acid bacteria fermentation extract, lactobacillus fermentation product, fermentation monosporus fermentation product extract, bifida ferment lysate fermentation product extract, yeast fermentation product, mushroom extract, Ganoderma lucidum extract, shiitake mushroom extract, sodium alginate, Inonotus obliquus extract, chondrus crispus, citric acid, and deacetylated chitosan; 0.01-10wt% Polysorbate-80; 0.01-50 wt% caprylic / capric triglycerides and the balance water.

2. The feminine care thixotropic gel according to claim 1, characterized in that: The mass ratio of the quaternized chitosan to tannic acid is 1-3:

1.

3. The feminine care thixotropic gel according to claim 1, characterized in that: The wall-to-core ratio of the sodium alginate-chitosan probiotic microcapsules is 1:3-4; the particle size of the sodium alginate-chitosan probiotic microcapsules is 30-50 micrometers.

4. The feminine care thixotropic gel according to claim 1, characterized in that: The sodium alginate that makes up the wall material of the sodium alginate-chitosan probiotic microcapsule has a molecular weight of 10-200 kDa, the chitosan has a molecular weight of 50-100 kDa, and the degree of deacetylation of the chitosan is ≥85%.

5. The feminine care thixotropic gel according to claim 1, characterized in that: The preparation method of the sodium alginate-chitosan probiotic microcapsules is as follows: A1. Dissolve sodium alginate powder in deionized water, heat in a water bath at 60-80℃ overnight, and then cool to room temperature to obtain a sodium alginate solution with a concentration of 1.5-2.5wt%. A2. Mix sodium alginate solution and probiotic extract compound solution at a wall-to-core ratio of 1:3-4, and homogenize to obtain a mixture; A3. Add the mixture dropwise into a 3-5% CaCl2 solidification solution, stir at a speed of 400-600 r / min, and then solidify to obtain calcium alginate gel microspheres; A4. After washing the calcium alginate microspheres with water, immerse them in a chitosan solution with a concentration of 0.75-1.0% and a pH of 4.5-5.0, continue stirring, wash with water, and obtain wet capsules; finally, freeze-dry under vacuum to obtain sodium alginate-chitosan probiotic microcapsules.

6. The feminine care thixotropic gel according to claim 1, characterized in that: In step A3, the drip rate of the mixture is 25-35 drops / minute; the curing temperature is 40-50℃. In step A4, the vacuum freeze-drying temperature is -15 to -25°C; the vacuum pressure is 500-500 Pa; and the drying time is 16-20 hours.

7. The feminine care thixotropic gel according to claim 1, characterized in that: The lactic acid constitutes 85.0-95.0% of the mass of the lactic acid solution, with the remainder being water.

8. The feminine care thixotropic gel according to claim 1, characterized in that: The aloe vera-mushroom repair gel has a mass percentage of 1-5 wt%. The chamomile extract has a mass percentage of 1-15 wt%; The PCO ternary preservative has a mass percentage of 0.8-1.5 wt%. The lactic acid solution has a mass percentage of 0.5-5 wt%. The allantoin has a mass percentage of 0.5-8 wt%. The sodium alginate-chitosan probiotic microcapsules have a mass percentage of 1-10 wt%.

9. The feminine care thixotropic gel according to claim 1, characterized in that: The quaternized chitosan has a mass percentage of 1-3 wt%; The tannic acid has a mass percentage of 0.5-1.5 wt%. The polysorbate-80 is 1-10 wt% by mass; The mass percentage of the caprylic / capric triglyceride is 1-50 wt%.

10. The method for preparing a feminine care thixotropic gel as described in claims 1-9, characterized in that: The preparation method includes the following steps: Step 1: Heat deionized water to 85-90℃ and maintain the temperature at 75-85℃; heat polysorbate-80 to 55-65℃. Step 2: Disperse the aloe vera-mushroom repair gel in deionized water; Step 3: After the product from Step 2 has cooled to 30-40℃, add quaternized chitosan, tannic acid, PCO ternary preservative and allantoin in sequence while stirring to obtain an aqueous phase. Step 4: Premix chamomile extract and caprylic / capric triglycerides, then add heated polysorbate-80, mix and stir to obtain the oil phase; Step 5: With stirring, continuously add the oil phase from Step 4 to the aqueous phase from Step 3. After stirring, add sodium alginate-chitosan probiotic microcapsules, and then add lactic acid solution as a pH adjuster to adjust the pH of the system to 3.8-5 to obtain the final product.

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