CN113975228A

CN113975228A - Gynecological antibacterial gel and application thereof

Info

Publication number: CN113975228A
Application number: CN202111208448.9A
Authority: CN
Inventors: 杨小荣; 郑子雯; 陈小丹
Original assignee: Jiangxi Cancer Hospital Jiangxi Second People's Hospital Jiangxi Cancer Center
Current assignee: Jiangxi Cancer Hospital Jiangxi Second People's Hospital Jiangxi Cancer Center
Priority date: 2021-10-18
Filing date: 2021-10-18
Publication date: 2022-01-28
Anticipated expiration: 2041-10-18
Also published as: CN113975228B

Abstract

The invention relates to the technical field of gynecological medical treatment, in particular to gynecological antibacterial gel for treating vaginitis. A gynecological antibacterial gel comprises matrine, repairing agent, gel matrix and adhesive with repairing function, wherein the adhesive with repairing function is mussel mucin. The gynecological antibacterial gel can effectively improve the killing rate of fungi, and particularly reduce the recurrence rate of vaginitis.

Description

Gynecological antibacterial gel and application thereof

Technical Field

The invention relates to the technical field of gynecological medical treatment, in particular to gynecological antibacterial gel for treating vaginitis.

Background

Vaginitis is an inflammatory disease caused by inflammatory changes in the vaginal mucosa, and the connective tissue under the mucosa, caused by pathogenic microorganisms. Mycotic vaginitis is a common type of vaginitis, is common in clinic, and the pathogenic bacteria of the vaginitis are mainly candida albicans. According to clinical statistics, the incidence rate of the mycotic vaginitis reaches 75 percent. If the control cannot be carried out in time, inflammation can invade internal genitalia organs, pelvic inflammation is induced, and the like, so that the physical and psychological health of a patient is seriously affected.

Clinically, the current broad-spectrum antifungal drugs are common drugs for clinically treating mycotic vaginitis, can eliminate infection pathogenic bacteria and improve clinical symptoms. According to the reports of the literature, satisfactory curative effect can be obtained by using oral antifungal drugs and Chinese herbal compound lotion to wash vagina or using Chinese herbal extracts such as matrine, zedoary turmeric oil and the like to prepare pessary for treatment.

However, compared with simple candidal vaginitis, the intractable candidal vaginitis is characterized by difficult radical cure and high recurrence rate, and the recurrence rate is reported to be 5% in documents. The patient can be diagnosed with recurrent mycotic vaginitis, also called refractory candida vaginitis, after the vaginal secretion candida examination result is positive for 4 times or more within 1 year.

The reasons for the high recurrence rate of the mycotic vaginitis are mainly that the flora balance is broken, pathogenic bacteria abnormally proliferate and the like due to the change of the physicochemical conditions of the internal environment of the vagina. The lotion of the traditional Chinese medicine preparation and the long-term use of the preparation are easy to cause the change of the internal environment of the vagina, and the repeated use of a large amount of antibiotics is an important reason for causing the repeated drug resistance and inflammation of candida. The existing treatment method aiming at simply killing candida albicans can achieve the curative effect and promote the occurrence of relapse.

How to prevent the recurrence of the colpitis mycotica is a difficult problem in the treatment of the gynecological vaginitis, but the current clinically used medicines and treatment methods cannot effectively solve the problem.

The matrine is extracted from herba Sophorae Alopecuroidis of Leguminosae, is white or light yellow, has antibacterial and antiinflammatory effects, and also has effects of promoting granulation and astringing. The matrine vaginal preparation is mainly used for treating mycotic vaginitis. If the matrine gel is reported in documents to treat 322 cases of mycotic vaginitis, the clinical cure rate is 37.89%, the significant efficiency is 32.61%, and the total effective rate is 96.89%, which shows that the matrine gel has better curative effect on simple mycotic vaginitis.

Madecassic acid, also known as asiaticoside, is a yellowish to pale brown-yellow powder; has no odor, bitter taste and slightly hygroscopicity, is a weakly acidic compound with large molecular weight, and has pharmacological effects of inhibiting fibroblast proliferation, resisting tumor and inflammation, and protecting cardiovascular system. Madecassic acid accelerates the healing of wound surfaces by activating epithelial tissues, inhibits the synthesis of collagen, and controls the excessive proliferation of stroma and fibrous components of connective tissues to play a role in treating scars, so that the madecassic acid can be widely applied to clinic to inhibit the proliferation of fibroblasts so as to treat fibrotic diseases such as burn scars and scleroderma, but no related application and research prove that the madecassic acid has a treatment effect or an auxiliary effect on mycotic vaginitis.

The position where the vaginitis occurs is the external genitalia of women, the structure is complex, the wrinkles of the skin and mucous membranes are more, the vagina has sweat glands and sebaceous glands, and also has secretions of vestibular glands, cervix uteri and vagina, and menstruation, so that the common external preparation is difficult to be attached to the affected part for a long time to play a role; in addition, some fungi are easily hidden in the wrinkles of the skin or the inflamed skin, and the existing external preparation is difficult to completely kill the fungi, so that the mycotic vaginitis is repeatedly relapsed.

Disclosure of Invention

The invention aims to provide the antibacterial gel for treating the mycotic vaginitis, which has good curative effect and low recurrence rate.

In order to achieve the purpose, the invention adopts the following technical scheme:

a gynecological antibacterial gel comprises matrine, repairing agent, gel matrix and adhesive with repairing function, wherein the adhesive with repairing function is mussel mucin.

Further, the repairing agent is madecassic acid, and the mussel mucin is mussel mucin mfp-3 or mussel mucin mfp-5.

Further, the antibacterial gel comprises the following components: contains 2 to 5 percent of 4 percent matrine ethanol solution, 0.5 to 2 percent of madecassic acid, 0.1 to 0.3 percent of mussel mucin, 0.3 to 1 percent of carbomer and purified water,

further, the pH of the gynecological antibacterial gel is 4.1-4.5.

Furthermore, the beverage also comprises other auxiliary materials, wherein the other auxiliary materials are essence and a PH regulator. The gel matrix is carbomer or sodium alginate.

Further, the matrine is a 4% matrine ethanol solution, and the mass ratio of the matrine to the madecassic acid to the mussel mucin is 3: 1: 0.2.

further, the antibacterial gel is prepared from the following components: 3.0% of 4% matrine ethanol solution, 1.0% of madecassic acid, mfp-50.2% of mussel mucin, 0.6% of carbomer, 0.02% of other auxiliary materials and the balance of purified water.

Application of gynecological antibacterial gel in preparing medicine for treating recurrent mycotic vaginitis is provided.

Application of gynecological antibacterial gel in ovarian cancer postoperative adjuvant medicine is provided.

The gynecological antibacterial gel disclosed by the invention can effectively kill pathogenic fungi of vaginitis by adopting a matrine ethanol solution, madecassic acid and mussel mucin mfp-5 in a specific mass ratio, and the strong adhesion and the repair action of the mussel mucin mfp-5 are utilized to prolong the action time of the gel on an affected part by utilizing the synergistic effect of the matrine ethanol solution, the madecassic acid and the mussel mucin mfp-5, so that the gynecological antibacterial gel can be used for continuously sterilizing and repairing inflammatory skin, the fungus killing rate can be effectively improved, and particularly the recurrence rate of vaginitis is reduced.

Detailed Description

Examples

Preparing an antibacterial gel:

the main component sources are as follows:

matrine: kyowa Kararray Biotechnology, Inc.;

madecassic acid: nanjing spring and autumn bioengineering, Inc.;

asiaticoside: nanjing spring and autumn bioengineering, Inc.;

mussel mucin, mussel mucin Mfp-5: zhejiang ocean university.

Inventive and control samples were prepared according to the following formula 1:

table 1:

sample 1 other adjuvants were essence and PH adjuster, with 0.01% of each ingredient.

Sample 1 preparation method:

(1) preparing a 4% matrine ethanol solution: weighing matrine extract, adding 95% ethanol according to calculated amount, and dissolving to obtain ethanol solution containing 4% matrine.

(2) Weighing madecassic acid, adding the madecassic acid into purified water, and heating to dissolve; adding 4% matrine ethanol solution of the prescription amount, and stirring uniformly; adding mussel mucin mfp-5, and stirring; weighing carbomer 940, uniformly dispersing on the liquid surface, keeping the liquid surface calm, adding essence after carbomer 940 is completely swelled, stirring uniformly, and adding a pH regulator to make the pH value of the gel reach 4.3.

In vitro antibacterial test

1. Test samples: samples 1 to 7 obtained in example 1, and a commercially available clotrimazole suppository;

culture medium: sabouraud glucose agar, and Sabouraud glucose liquid culture medium.

Strain: candida albicans isolated from leucorrhea and cervical secretion specimens of patients with clinical vaginitis was identified by germ tube formation test, pachytene spore formation test, and mouse pathogenic test.

2. Experimental methods

By adopting a bacteria collection mixing and dosing method, 20ml of molten and cooled Sha's dextrose agar at 45 ℃ is poured into a sterilization plate with the inner diameter of 9cm for solidification. A plurality of culture plates are prepared in this way, a standard inoculating loop is used for picking a dilution bacterium solution with the tricyclic concentration of 104CFU/ml, intensive streak inoculation is carried out on a plate, sterilized Oxford cups with the inner diameter of 6mm are used, and 6 tubes are placed on the surface of a culture medium at equal intervals. Respectively sucking 50ul of the compound liquid medicine by a microsyringe, adding into the holes, culturing in a 37 ℃ incubator for 48h, measuring the diameter value of the zone of inhibition, repeating the experiment for 3 times, and taking the average value of 3 times as the diameter of inhibition, which is shown in Table 2.

3. Results of the experiment

Table 2: experimental results of zone of inhibition

Test for resisting infection of rabbit vagina mucosa with artificial fungus

72 rabbits, females, weighing 1.9. + -. 0.5 kg, were randomly divided into 9 groups of 8 rabbits each. Except for the blank group, 0.1ml of candida albicans bacterial liquid (about 10 hundred million bacteria contained in each ml) is extracted from the other 8 groups by an inoculation injection needle and injected into the vagina of the rabbit at a depth of about 3-4 cm, before the bacterial liquid is injected, the needle is attached to the vagina and repeatedly moves forwards, backwards, leftwards and rightwards for 7-8 times to cause local damage to the vagina mucosa, and then the bacterial liquid is injected. Starting 24 hours after fungus inoculation, continuously injecting distilled water into the vagina of the rabbits of the blank group and the model group for 7 days, and respectively coating the other groups with 0.5g of samples 1-6 and clotrimazole suppository on the inner wall of the vagina of the rabbits. After the treatment is finished, collecting vaginal local secretion to detect fungi and culturing the fungi. The results are shown in Table 3.

Table 3: curative effect of artificial fungal infection of rabbit vaginal mucosa

The above experimental results show that the samples 1, 2, 5, 7 and clotrimazole suppository group have a good therapeutic effect, and the fungi are substantially disappeared.

Experiment of recurrence rate of vaginal fungal infection in rabbits

The rabbits in each group after the treatment course are continuously raised for 14 days, during which time normal diet and activity are maintained. After 14d, the animals are sacrificed for vaginal smear examination, vaginal local secretion is collected for fungus culture, and finally the vagina is examined for pathological sections. The results are shown in Table 4.

Table 4: the recurrence of vaginal mucosa fungal infection of rabbit.

The experimental results in the table show that the mycotic vaginitis of the rabbits using the sample 1 obtained by the invention has no recurrence after two weeks of treatment, and the vagina inner wall has no inflammation according to pathological section; the other groups had different degrees of recurrence, probably due to the strong adhesiveness of mussel mucin mfp-5 prolonging the duration of action of the gel on the affected area, the synergistic effect of common parameters of mussel mucin mfp-5 and madecassic acid, and the better anti-inflammatory action and reparative ability of the gel due to mussel mucin mfp-5 and madecassic acid having reparative action. The mussel mucin mfp-5 of the invention can be extracted naturally, or can be obtained by expression, separation and purification of Escherichia coli, yeast or CHO cells.

Under a healthy state, the pH value of the vagina is acidic, and the pH value of the gel is too high, so that the acid-base imbalance of the vagina is caused, and the bacteriostatic effect is influenced. The adhesiveness of the mussel mucin is enhanced along with the increase of the pH value, the adhesiveness of the mussel mucin is reduced under the condition of low pH in the vaginal environment, and the mussel mucin mfp-5 is high in DOPA content in the mussel mucin and is also strongest in the adhesiveness. Generally, when the mussel mucin mfp-5 is used as gel, the pH value is not less than 7, the higher the pH value is, the better the adhesion performance is, but the pH value of the gel disclosed by the invention is too high, so that the acid-base imbalance of the vagina can be caused, and the bacteriostatic effect is influenced. The content of mussel mucin mfp-5 and the special proportion of matrine and madecassic acid are used to this patent for the gel still can keep stronger adhesion effect under the environment of low PH, can prolong the action time of gel in the affected part for the gel that uses ordinary mussel mucin, makes antibacterial effect better, prevents the relapse after the vaginitis cures.

And (3) heavy metal detection of the antibacterial gel:

first, equipment

1. Test samples: sample 1 from example 1;

2. the instrument equipment comprises: atomic fluorescence photometer, type: BAF-2000; atomic absorption spectrophotometer, model: AA-6880F/AAC; electronic balance, model: JA 5003N.

3. Standard solutions and concentrations: mercury standard solution (10 ug/L); arsenic standard solution (100 ug/L); lead standard solution (50 mg/L).

Second, method

The detection basis is as follows: chapter iv physical and chemical detection method of cosmetic safety technical Specification (2015 edition) 1.2 Mercury first method; 1.4 arsenic first process; 1.3 lead second method.

Three, result in

The heavy metal test results of the samples are shown in Table 6

Table 5 heavy metal test results for samples

Fourth, conclusion

The gynecological antibacterial gel of the sample 1 provided by the embodiment of the invention has the mercury content of 0.002mg/kg, the arsenic content of 0.02mg/kg and the lead content of less than 1.5 mg/kg.

Detecting the pH value of the gynecological antibacterial gel:

first, equipment

1. Test samples: sample 1 from example 1;

2. the instrument equipment comprises: acidimeters, type: PHS-25.

3. Calibration standard buffer solution: pH of potassium hydrogen phthalate solution (25 ℃ C.) was 4.00

Phosphate buffer solution pH (25 ℃ C.) 6.86

Borate standard buffer solution pH (25 ℃ C.) 9.18

Second, method

1. The detection basis is as follows: disinfection protocol (2002 edition) 2.2.1.4 determination of pH.

2. Detection conditions are as follows: the ambient temperature was 27.2 ℃ and the relative humidity was 64%. The number of test repetitions: 2 times.

3. Sample detection: the pH of the sample was measured directly (25 ℃).

Three, result in

The pH (25 ℃) of this sample was 4.30, and the results are shown in Table 6.

TABLE 6 test results of pH (25 ℃) of gynecological antibacterial gels

Fourth, conclusion

The pH (25 ℃) of the gynecological antibacterial gel of sample 1 of the embodiment of the invention was 4.30.

Claims

1. A gynecological antibacterial gel comprises matrine, repairing agent, gel matrix and adhesive with repairing function, and is characterized in that the adhesive with repairing function is mussel mucin.

2. A gynecological antiseptic gel according to claim 1, characterized in that the restorative agent is madecassic acid and the mussel mucin is mussel mucin mfp-3 or mussel mucin mfp-5.

3. A gynecological antiseptic gel according to claim 2, characterized by comprising the following components: the composition comprises 2-5% of 4% matrine ethanol solution, 0.5-2% of madecassic acid, 0.1-0.3% of mussel mucin, 0.3-1% of carbomer and purified water.

4. A gynaecological antiseptic gel according to claim 1 or 2, characterised in that the gynaecological antiseptic gel PH is 4.1-4.5.

5. A gynaecological antiseptic gel according to claim 1 or 2, further comprising other excipients, wherein the gel matrix is carbomer or sodium alginate.

6. A gynecological antiseptic gel according to claim 5 characterized in that the other excipients are a perfume and a pH regulator.

7. A gynecological antibacterial gel according to claim 2, characterized in that the matrine is a 4% matrine ethanol solution, the mass ratio of matrine, madecassic acid and mussel mucin is 3: 1: 0.2.

8. a gynecological antiseptic gel according to claim 2 characterized by being prepared from the following components: 3.0% of 4% matrine ethanol solution, 1.0% of madecassic acid, mfp-50.2% of mussel mucin, 0.6% of carbomer, 0.02% of other auxiliary materials and the balance of purified water.

9. Use of a gynaecological antimicrobial gel according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of recurrent mycotic vaginitis.

10. The use of a gynecological antiseptic gel according to any one of claims 1 to 8 in an adjuvant drug after ovarian cancer surgery.