Traditional Chinese medicine gel composition for vaginal mucosa bacteriostasis and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine gel composition for vaginal mucosa bacteriostasis and a preparation method thereof, and belongs to the technical field of biological medicine. The composition is prepared from extracts of nine traditional Chinese medicines including radix sophorae flavescentis, fructus cnidii, radix stemonae and the like and a carbomer-xanthan gum-hydroxyethyl cellulose ternary compound matrix through an ultrasonic-water decoction combined extraction process. The traditional Chinese medicine extracts synergistically achieve broad-spectrum bacteriostasis, the inhibition rates on staphylococcus aureus, escherichia coli and candida albicans are all larger than or equal to 90%, the ternary matrix film forming time is shorter than or equal to 3 minutes, continuous attachment in the vagina is longer than or equal to 8 hours, and the vaginal mucosa stimulation response score is smaller than or equal to 0.5. The gel solves the problems of limited antibacterial spectrum, slow film formation, short adhesion time and insufficient mucous membrane repair ability of the existing gel, is suitable for treatment of bacterial vaginitis and monilial vaginitis, and has the advantages of high efficiency, safety and high patient compliance.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and particularly relates to a traditional Chinese medicine gel composition for inhibiting bacteria on the vaginal mucosa and a preparation method thereof, which is particularly suitable for local treatment of gynecological vaginal infections and mucosa repair. BACKGROUND

[0002] Vaginal infection is a common reproductive system disease in women, mainly including bacterial vaginitis, candidal vaginitis, etc., and its incidence is closely related to vaginal micro-ecological imbalance and damaged mucosal barrier. At present, the commonly used treatment methods in the clinic include antibiotic suppositories, chemically synthesized antibacterial gels, etc., but there are the following technical defects: 1. Limited antibacterial spectrum: single component (such as metronidazole, clotrimazole) is only effective against specific pathogens, and cannot cover common pathogenic bacteria such as Staphylococcus aureus, Escherichia coli and Candida albicans at the same time, which easily leads to treatment failure of mixed infection; 2. Insufficient mucosa repair capacity: traditional gels lack active ingredients for promoting epithelial cell proliferation, and the damaged mucosa heals slowly (average repair time > 7 days), increasing the risk of recurrence; 3. Defects in gel matrix performance: existing preparations mostly use single carbomer matrix, and the retention time in the vagina is short (< 4 hours), which requires frequent administration (2-3 times per day), and the patient compliance is poor; 4. Safety hazards: some chemically synthesized antibacterial agents (such as chlorhexidine) can cause vaginal mucosa irritation (irritation score > 1.0), and long-term use may destroy the balance of vaginal micro-ecology.

[0003] Traditional Chinese medicine gels have become a research hotspot due to their advantages such as multi-component synergistic effect and high safety, but the existing technology still has deficiencies: for example, only single antibacterial components such as Sophora flavescens and Cnidium monnieri are used for prescription, and there is a lack of systematic optimization of mucosa repair and matrix performance; or traditional decoction extraction process is used, and the dissolution rate of effective components is low (< 30%), which leads to unstable antibacterial effect. Therefore, developing a traditional Chinese medicine gel composition with broad-spectrum antibacterial, rapid film-forming, long-acting adhesion and mucosa repair functions has become the key to solving the defects of the existing technology. SUMMARY

[0004] In view of the technical defects of the existing vaginal antibacterial gel, such as limited antibacterial spectrum, insufficient mucosa repair capacity, slow film-forming and short adhesion time of the gel matrix, and poor safety, the present application provides a traditional Chinese medicine gel composition for inhibiting bacteria on the vaginal mucosa and a preparation method thereof, which realizes the technical effects of broad-spectrum antibacterial, rapid film-forming, long-acting adhesion and low mucosa irritation through synergistic compatibility of multi-herbal extracts and innovative design of ternary composite matrix, and solves the problems of poor treatment effect on mixed infection and low patient compliance of traditional preparations.

[0005] In order to achieve the above-mentioned purposes, the following technical solutions are adopted in the present application: A traditional Chinese medicine gel composition for inhibiting bacteria in vaginal mucosa, which is composed of the following raw materials in parts by weight: 15-25 parts of Sophora flavescens extract, 8-15 parts of Cnidium monnieri extract, 5-10 parts of Stemona sessilifolia extract, 3-7 parts of Panax ginseng extract, 2-5 parts of Cimicifuga foetida extract, 3-6 parts of Cynomorium songaricum extract, 4-8 parts of Rhus semialata extract, 5-10 parts of Aloe vera extract, 3-6 parts of Punica granatum peel extract, 1-3 parts of borneol, 1-3 parts of menthol, 1-2 parts of sodium hyaluronate, 1-3 parts of carbomer, 0.5-1.5 parts of xanthan gum, 0.8-1.2 parts of hydroxyethyl cellulose, and the rest is purified water.

[0006] Preferably, the parts by weight of the traditional Chinese medicine extract are as follows: 20 parts of Sophora flavescens extract, 12 parts of Cnidium monnieri extract, 8 parts of Stemona sessilifolia extract, 5 parts of Panax ginseng extract, 3 parts of Cimicifuga foetida extract, 4 parts of Cynomorium songaricum extract, 6 parts of Rhus semialata extract, 7 parts of Aloe vera extract, and 5 parts of Punica granatum peel extract.

[0007] Preferably, in the composition, the carbomer, xanthan gum and hydroxyethyl cellulose form a ternary composite matrix, and the weight ratio of the three is 3:1:1, the film forming time of the composite matrix in the vagina is ≤3 minutes, and the film layer lasts for ≥8 hours.

[0008] The application further provides a preparation method of the composition, which comprises the following steps: (1) mixing extraction: mixing Sophora flavescens, Cnidium monnieri, Stemona sessilifolia, Panax ginseng, Cimicifuga foetida, Cynomorium songaricum, Rhus semialata, Aloe vera and Punica granatum peel, adding 8-10 times the amount of purified water, soaking for 1 hour, and then performing ultrasonic-water decoction combined extraction twice, combining the filtrates, and concentrating under reduced pressure to a relative density of 1.10-1.15 to obtain a traditional Chinese medicine extract; (2) preparation of a composite matrix: mixing carbomer, xanthan gum and hydroxyethyl cellulose according to a weight ratio of 3:1:1, and adding purified water to swell for 24 hours; (3) molding: uniformly mixing the traditional Chinese medicine extract, borneol, menthol ethanol solution and sodium hyaluronate water solution, slowly adding the composite matrix of step (2), stirring for 30 minutes, adding triethanolamine to adjust the pH to 5.0-6.0, stirring until a transparent gel is formed, and then performing dispensing.

[0009] Further, the gel composition has an inhibition rate of ≥90% on Staphylococcus aureus, Escherichia coli and Candida albicans, a vaginal mucosa irritation reaction score of ≤0.5, and a gel erosion rate of ≤15% in a 24-hour simulated vaginal environment at 37°C.

[0010] The application further discloses application of the composition in preparation of a medicine for treating bacterial vaginitis and candidal vaginitis.

[0011] With the above scheme, the application has the following advantages: 1. Broad-spectrum and high-efficiency bacteriostasis: the inhibition rate of Staphylococcus aureus, Escherichia coli and Candida albicans is all ≥90%, which can cover the common pathogenic bacteria of bacterial vaginitis and candidal vaginitis, and solve the problem of limited bacteriostasis spectrum of traditional preparations; 2. Rapid repair of mucosa: through the synergistic effect of ginseng and cynomorium extract, the repair time of vaginal mucosa damage is shortened to 3-5 days (compared with 7-10 days of the prior art), and the mucosa irritation reaction score is ≤0.5, and the safety is significantly improved; 3. Long-acting sustained release and high compliance: the ternary compound matrix realizes rapid film formation (≤3 minutes) and long-acting adhesion (≥8 hours), and the effective drug concentration can be maintained by once-a-day administration, and the patient compliance is improved by more than 60%; 4. Stable and controllable process: the ultrasonic-water decoction combined extraction process makes the effective component content RSD ≤5% (n=3), ensures the batch-to-batch quality consistency, and meets the GMP production requirements.

[0012] The application overcomes the technical defects of the existing gel through the synergistic effect of multiple components of traditional Chinese medicine and the innovation of preparation technology, and provides a safe, efficient and convenient new choice for the local treatment of vaginal infection. DETAILED DESCRIPTION

[0013] The technical solutions of the application will be described below in detail with specific embodiments of the application. Obviously, the described embodiments are part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor belong to the protection scope of the application. The embodiments are only used to explain the application, and do not limit the protection scope of the application.

[0014] Embodiment 1 1. Raw material composition (weight parts) 15 parts of Sophora flavescens extract, 8 parts of Cnidium fruit extract, 5 parts of Stemona sessilifolia extract, 3 parts of Panax ginseng extract, 2 parts of Cimicifuga foetida extract, 3 parts of Cynomorium songaricum extract, 4 parts of Rhus semialata extract, 5 parts of Aloe vera extract, 3 parts of Punica granatum peel extract, 1 part of borneol, 1 part of menthol, 1 part of sodium hyaluronate, 1 part of carbomer, 0.5 part of xanthan gum, 0.8 part of hydroxyethyl cellulose, and the balance is purified water.

[0015] 2. Preparation method (1) Mixed extraction: mix Sophora flavescens, Cnidium monnieri, Farfarae, Panax ginseng, Cimicifuga foetida, Cynomorium songaricum, Galogia tinctoria, Aloe vera, Punica granatum, add 8 times the amount of purified water, soak for 1 hour, then use ultrasonic-water decoction combined extraction (power 300W, temperature 60℃) for 2 times (1 hour each time), combine the filtrate, concentrate under reduced pressure to relative density 1.10 (60℃), get the traditional Chinese medicine extract; (2) Compound matrix preparation: take carbomer, xanthan gum, hydroxyethyl cellulose in a weight ratio of 3:1:1 (i.e. carbomer 1 part, xanthan gum 0.33 part, hydroxyethyl cellulose 0.33 part, the rest is supplemented to the formula amount), add purified water and swell for 24 hours; (3) Forming: mix the traditional Chinese medicine extract with borneol, menthol, sodium hyaluronate uniformly, slowly add the compound matrix of step (2), stir for 30 minutes, then add triethanolamine and stir until transparent gel, adjust the pH to 5.0, and then pack.

[0016] 3. Performance test results Bacteriostatic rate: 90% for Staphylococcus aureus, 91% for Escherichia coli, and 90% for Candida albicans; Film forming time: 3 minutes; Film layer adhesion time: 8 hours; Vaginal mucosa irritation reaction score: 0.5 (test standard GB / T 16886.10-2017); 37℃ simulated vaginal environment 24 hours dissolution rate: 15%.

[0017] Example 2 1. Raw material composition (weight parts) Sophora flavescens extract 20 parts, Cnidium monnieri extract 12 parts, Farfarae extract 8 parts, Panax ginseng extract 5 parts, Cimicifuga foetida extract 3 parts, Cynomorium songaricum extract 4 parts, Galogia tinctoria extract 6 parts, Aloe vera extract 7 parts, Punica granatum extract 5 parts, borneol 2 parts, menthol 2 parts, sodium hyaluronate 1.5 parts, carbomer 2 parts, xanthan gum 1 part, hydroxyethyl cellulose 1 part, and the rest is purified water.

[0018] 2. Preparation method (1) Mixed extraction: add 10 times the amount of purified water, ultrasonic-water decoction combined extraction (power 300W, temperature 60℃) for 2 times, concentrate to relative density 1.12 (60℃); (2) Compound matrix preparation: mix carbomer, xanthan gum, and hydroxyethyl cellulose in a ratio of 3:1:1 (2 parts:0.67 parts:0.67 parts, the rest is supplemented to the formula amount), add purified water and swell for 24 hours; (3) Adjust the pH to 5.5, and the rest of the steps are the same as in Example 1.

[0019] 3. Performance test results Bacteriostatic rate: 96% for Staphylococcus aureus, 95% for Escherichia coli, and 97% for Candida albicans; Film forming time: 2 minutes; Film layer adhesion time: 10 hours; Vaginal mucosa irritation reaction score: 0.3 (test standard GB / T 16886.10-2017); 37℃ simulated vaginal environment for 24 hours dissolution rate: 10%.

[0020] Example 3 1. Raw material composition (weight parts) Sophora flavescens extract 25 parts, Cnidium fruit extract 15 parts, Stemona sessilifolia extract 10 parts, Panax ginseng extract 7 parts, Cimicifuga racemosa extract 5 parts, Cynomorium songaricum extract 6 parts, Rhus succedaneum extract 8 parts, Aloe extract 10 parts, Punica granatum peel extract 6 parts, borneol 3 parts, menthol 3 parts, sodium hyaluronate 2 parts, carbomer 3 parts, xanthan gum 1.5 parts, hydroxyethyl cellulose 1.2 parts, and the balance is purified water.

[0021] 2. Preparation method (1) Mixed extraction: add 9 times the amount of purified water, and then extract by ultrasonic-water decoction combination and concentrate to a relative density of 1.15 (60℃); (2) Compound matrix preparation: mix carbomer, xanthan gum and hydroxyethyl cellulose at a ratio of 3:1:1 (3 parts:1 part:1 part), and then add purified water to swell for 24 hours; (3) Adjust the pH to 6.0, and the remaining steps are the same as in Example 1.

[0022] 3. Performance test results Bacteriostatic rate: 95% for Staphylococcus aureus, 94% for Escherichia coli, and 96% for Candida albicans; Film forming time: 2.5 minutes; Film layer adhesion time: 9 hours; Vaginal mucosa irritation reaction score: 0.4 (test standard GB / T 16886.10-2017); 37℃ simulated vaginal environment for 24 hours dissolution rate: 12%.

[0023] Comparative Example 1 1. Raw material composition: the same as in Example 2 except that it does not contain hydroxyethyl cellulose (i.e. carbomer 2 parts, xanthan gum 1 part, and no hydroxyethyl cellulose).

[0024] 2. Performance test results: Film forming time: 8 minutes (unable to form film quickly); Film layer adhesion time: 3 hours (adhesion time significantly shortened); Dissolution rate: 35% (a large amount of dissolution within 24 hours, drug burst release).

[0025] Comparative Example 2 1. Preparation method: the same as Example 2 except that the extraction step only used water decoction (no ultrasonic).

[0026] 2. Performance test results: Bacteriostatic rate: 75% for Staphylococcus aureus, 72% for Escherichia coli, and 70% for Candida albicans (low effective component dissolution rate, and decreased bacteriostatic effect) ; Effective component content: matrine content decreased by 45% compared with Example 2 (HPLC detection).

[0027] Comparative Example 3 1. Raw material composition: the same as Example 2 except that it does not contain ginseng extract and horny goat weed extract.

[0028] 2. Performance test results: Vaginal mucosa irritation score: 0.4 (no significant difference) ; Mucosa repair rate: 15 μm / day (significantly decreased compared with 40 μm / day of Example 2, and decreased repair ability).

[0029] Comparison and analysis of examples and comparative examples 1. Necessity of ternary composite matrix (comparing Example 2 and Comparative Example 1) : only using carbomer and xanthan gum cannot form a stable three-dimensional network structure, resulting in prolonged film formation time and shortened adhesion time, proving the key role of hydroxyethyl cellulose in the matrix; 2. Advantages of ultrasonic-water decoction combined extraction (comparing Example 2 and Comparative Example 2) : the effective component dissolution rate is low by traditional water decoction method, and the bacteriostatic effect is decreased by about 40%, verifying that the extraction process of the present application can significantly improve the efficacy; 3. Mucosa repair effect of ginseng and horny goat weed (comparing Example 2 and Comparative Example 3) : when lacking the two, the mucosa repair rate is decreased by 62.5%, proving the synergistic effect of the two in promoting mucosa healing.

Claims

1. A traditional Chinese medicine gel composition for inhibiting bacteria in the vaginal mucosa, characterized in that, consists of the following raw materials by weight: 15-25 parts of Sophora flavescens extract, 8-15 parts of Cnidium monnieri extract, 5-10 parts of Stemona sessilifolia extract, 3-7 parts of Panax ginseng extract, 2-5 parts of Cimicifuga foetida extract, 3-6 parts of Cynomorium songaricum extract, 4-8 parts of Rhus semialata extract, 5-10 parts of Aloe vera extract, 3-6 parts of Punica granatum peel extract, 1-3 parts of borneol, 1-3 parts of menthol, 1-2 parts of sodium hyaluronate, 1-3 parts of carbomer, 0.5-1.5 parts of xanthan gum, 0.8-1.2 parts of hydroxyethyl cellulose, and the balance being purified water.

2. The composition of claim 1, wherein, The weight parts of the traditional Chinese medicine extract are preferably: 20 parts of Sophora flavescens extract, 12 parts of Cnidium monnieri extract, 8 parts of Stemona sessilifolia extract, 5 parts of Panax ginseng extract, 3 parts of Cimicifuga foetida extract, 4 parts of Cynomorium songaricum extract, 6 parts of Rhus semialata extract, 7 parts of Aloe vera extract, and 5 parts of Punica granatum peel extract.

3. The composition of claim 1, wherein, The carbomer, xanthan gum, and hydroxyethyl cellulose form a ternary composite matrix, and the weight ratio of the three is 3:1:

1. The film-forming time of the composite matrix in the vagina is ≤3 minutes, and the film layer has a sustained adhesion time of ≥8 hours.

4. A method for preparing a traditional Chinese medicine gel composition for inhibiting bacteria in the vaginal mucosa, characterized in that, The method comprises the following steps: (1) mixing and extracting: mixing Sophora flavescens, Cnidium monnieri, Stemona sessilifolia, Panax ginseng, Cimicifuga foetida, Cynomorium songaricum, Rhus semialata, Aloe vera, and Punica granatum peel, adding 8-10 times the amount of purified water, soaking for 1 hour, and then extracting twice by ultrasonic and water decoction, combining the filtrates, and concentrating under reduced pressure to a relative density of 1.10-1.15 to obtain a traditional Chinese medicine extract; (2) preparing a composite matrix: mixing carbomer, xanthan gum, and hydroxyethyl cellulose at a weight ratio of 3:1:1, and swelling in purified water for 24 hours; (3) forming: uniformly mixing the traditional Chinese medicine extract, borneol, menthol ethanol solution, and sodium hyaluronate water solution, slowly adding the composite matrix of step (2), stirring for 30 minutes, then adding triethanolamine and stirring until a transparent gel is formed, adjusting the pH to 5.0-6.0, and then dispensing.

5. The composition according to any one of claims 1 to 3, characterized in that, The gel has an inhibition rate of ≥90% for Staphylococcus aureus, Escherichia coli, and Candida albicans, a vaginal mucosa irritation reaction score of ≤0.5, and a gel erosion rate of ≤15% in a simulated vaginal environment at 37°C for 24 hours.

6. Use of the composition of any one of claims 1-3 in the preparation of a medicament for treating bacterial vaginitis and candidal vaginitis.