阅读说明：本技术 一种***抑菌制剂及其制备方法 (Vaginal antibacterial preparation and preparation method thereof ) 是由 张义淦 陈寻丹 陈嘉敏 于 2019-09-22 设计创作，主要内容包括：本发明公开了一种阴道抑菌制剂及其制备方法,属于药物制剂技术领域,阴道抑菌制剂为多层结构,从内至外依次包括益生菌层、隔离层、抑菌层,各层的质量比为1:0.5-3:0.5-6；所述益生菌层包括益生菌、基体材料；所述隔离层包括明胶；所述抑菌层包括水凝胶、抑菌组合物。本发明的阴道抑菌制剂兼具抑菌、隔离和促益生菌增殖的作用,通过生物调节的方法,维持阴道内菌群的生态平衡,对人体刺激性小,治疗阴道炎疗效显著、持续时间长、不易复发,且使用方便。(The invention discloses a vaginal bacteriostatic preparation and a preparation method thereof, belonging to the technical field of pharmaceutical preparations, wherein the vaginal bacteriostatic preparation is of a multilayer structure and sequentially comprises a probiotic layer, an isolation layer and a bacteriostatic layer from inside to outside, wherein the mass ratio of each layer is 1:0.5-3: 0.5-6; the probiotic layer comprises probiotics and a matrix material; the isolation layer comprises gelatin; the bacteriostatic layer comprises hydrogel and a bacteriostatic composition. The vagina bacteriostatic preparation has the functions of bacteriostasis, isolation and promoting the proliferation of probiotics, maintains the ecological balance of flora in the vagina by a biological regulation method, has small irritation to human bodies, has obvious curative effect of treating vaginitis, long duration, difficult relapse and convenient use.)

1. A vaginal bacteriostatic preparation comprises probiotics and a bacteriostatic composition, and is characterized in that: the vagina bacteriostatic preparation is of a multilayer structure and sequentially comprises a probiotic layer, an isolation layer and a bacteriostatic layer from inside to outside, wherein the mass ratio of each layer is 1:0.5-3: 0.5-6;

the probiotic layer comprises probiotics and a matrix material; 3-26 parts of probiotics and 70-97 parts of matrix material by mass;

the isolation layer comprises gelatin;

the bacteriostatic layer comprises hydrogel and a bacteriostatic composition; 47-98 parts of hydrogel and 2-55 parts of bacteriostatic composition by mass.

2. The bacteriostatic vaginal formulation of claim 1, wherein: the probiotics is one or more of lactobacillus acidophilus, lactobacillus rhamnosus, lactobacillus plantarum and lactobacillus fermentum.

3. The bacteriostatic vaginal formulation of claim 1, wherein: the matrix material is a high molecular compound or a composition thereof.

4. The bacteriostatic vaginal formulation of claim 3, wherein: the polymer compound is one or more of gelatin, polyethylene glycol, polyvinyl alcohol, starch, cellulose and polyacrylic acid.

5. The bacteriostatic vaginal formulation of claim 1, wherein: the isolating layer also comprises an auxiliary agent; the auxiliary agent is one or more of sucrose, maltose, lactose, fructo-oligosaccharide, cellulose, panose, protein, unsaturated fatty acid, glycerol and triglyceride.

6. The bacteriostatic vaginal formulation of claim 5, wherein: the gelatin and the auxiliary agent are mixed according to the mass portion of 30-80 parts of gelatin and 5-35 parts of auxiliary agent.

7. The bacteriostatic vaginal formulation of claim 1, wherein: the hydrogel is one or two of aloe gel and gelatin hydrogel.

8. The bacteriostatic vaginal formulation of claim 1, wherein: the antibacterial composition is at least two of A.SAP antibacterial agent, chlorhexidine acetate, octoxynol, ammonium alginate, nifuratel, nysfungin, Corni fructus, cortex Phellodendri, radix Stemonae, flos Chrysanthemi Indici, herba Violae, Eucalyptus robusta, rhizoma corydalis, indigo naturalis, Camphora, fructus Cnidii, stigma croci Sativi, radix Sophorae Flavescentis, oleum Hippophae, Olibanum, and Myrrha.

9. A method of preparing a bacteriostatic formulation for the vagina according to any one of claims 1 to 8, comprising the steps of:

(1) taking probiotic strains, inoculating the probiotic strains in a culture medium under an aseptic condition for culture, and collecting cultured probiotic strains; dissolving the matrix material in water at 60-100 ℃, cooling to 40-55 ℃ after completely dissolving, adding probiotic bacteria and uniformly mixing to obtain a probiotic bacteria layer material;

(2) heating the gelatin to melt the gelatin, and cooling to 50-60 ℃ to obtain an isolation layer material;

(3) adding the antibacterial composition into the hydrogel, and uniformly mixing to obtain an antibacterial layer material;

(4) taking the probiotic layer material with the formula amount, adding the probiotic layer material into a mold, and cooling and molding at room temperature to obtain a probiotic layer; uniformly coating the surface of the probiotic layer with the isolating layer material according to the formula amount at the temperature of 50-60 ℃, and cooling and forming at room temperature to obtain a semi-finished product of the probiotic layer coated by the isolating layer; and finally, uniformly coating the surface of the semi-finished product with the bacteriostatic layer material according to the formula amount, pre-freezing and forming at the temperature of-5-0 ℃, further solidifying and forming at room temperature, and packaging to obtain the finished product.

10. A method of preparing a bacteriostatic vaginal formulation as claimed in claim 9 wherein: and (3) sterilizing the gelatin in the step (2).

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a vaginal antibacterial preparation and a preparation method thereof.

Background

Vaginitis is a common female disease, which is caused by a special physiological structure of a female, a large number of fold dead corners exist in the female vagina and are not easy to clean, the body resistance of the female during menstruation and pregnancy is reduced, harmful bacteria can be bred in a large amount at the moment, the normal ecological balance in the female vagina is destroyed, and then vaginitis is caused, the clinical manifestations of the vaginitis include symptoms such as pruritus, burning pain, abnormal leucorrhea and the like, and serious discomfort is brought to the female body, so that the female vaginitis needs to be treated in time, and the physical and psychological health of the female is ensured. The treatment of vaginitis can be started from the following two aspects:

first, beneficial bacteria are supplemented. The external beneficial bacteria are implanted into the vagina, and the proliferation of harmful bacteria is inhibited through the growth of the beneficial bacteria, so that the vaginitis is treated. Chinese patent CN1097126A (active lactobacillus capsule) discloses a lactobacillus capsule for treating vaginitis and cervical erosion, which is prepared by adding active lactobacillus into excipient prepared by mixing medical starch and calcium carbonate to prepare viable bacteria powder, then filling the viable bacteria powder into medical capsule, and changing the physiological environment in vagina by adopting a vaginal administration method to promote the growth of lactobacillus so as to treat bacterial vaginitis. Chinese patent No. CN106047767 (a microbial powder additive for sanitary napkins and panty liners and a preparation method thereof) discloses a method for treating vaginitis by adding beneficial bacteria on a sanitary napkin, culturing beneficial bacteria such as lactobacillus acidophilus, and making into lyophilized powder, and introducing the lyophilized powder into female vagina through the sanitary napkin, panty liner, and the like, so as to introduce the beneficial bacteria into the vagina and further maintain the microbial environment balance in the vagina. The method can radically cure vaginitis theoretically, however, external beneficial bacteria suddenly enter the vaginal environment, the living environment is hard to proliferate due to mutation, in addition, the growth conditions of the flora in the vagina are basically the same, and the growth of harmful bacteria is hard to be effectively inhibited in actual operation, so the clinical treatment period is long, and the effect is not obvious.

Secondly, harmful bacteria are killed. A large amount of anaerobic bacteria including beneficial bacteria such as lactobacillus and bifidobacterium and harmful bacteria such as escherichia coli, staphylococcus and streptococcus exist in the vagina of a normal female, and the harmful bacteria can be killed. Chinese patent CN105233118A (a suppository formula for treating gynecological vaginitis and its preparation method) adopts a Chinese medicinal formula, and uses Stemona root, flos Chrysanthemi Indici, herba Violae, etc. to kill bacteria, discharge toxin, and treat inflammation; myrrh, frankincense and the like are used for promoting qi and blood circulation and improving the immunity of the organism; simultaneously, the aloe gel and the gelatin are adopted, so that the medicine can fully exert the function. Chinese invention patent CN105963340A (a vaginal antibacterial composition and its preparation and preparation method) mainly uses octoxynol, a.sap antibacterial agent, folium isatidis extract and ammonium alginate as raw materials, and adds them into a compound using carbomer as the main raw material to make into gel, so as to obtain the vaginal antibacterial composition. However, the method adopts chemical drugs, which can kill harmful bacteria in vagina and treat vaginitis, but also kill beneficial bacteria such as lactobacillus and the like at the same time of killing the harmful bacteria, and destroy the normal acid-base balance in the vagina, so that the vagina disease is easy to relapse.

In conclusion, it can be seen that neither simple bacteriostasis nor beneficial bacteria supplementation can completely and effectively treat the vaginal inflammation, but the combination of bacteriostasis and beneficial bacteria supplementation has the problem of low survival rate of beneficial bacteria, for example, chinese invention patent CN106177270A (a vaginal bacteriostasis preparation and a preparation method thereof) uniformly mixes lactobacillus rhamnosus and lactobacillus plantarum and then encapsulates the mixture in an aluminum plastic film, when in use, the mixture is mixed with aloe gel which is separately placed in a glass bottle and immediately pushed into the vagina of a woman, the method can maximally ensure the activity of the beneficial bacteria, and the aloe gel can also kill harmful bacteria, but the usage method of the bacteriostasis preparation is complex, and the operation convenience is greatly reduced.

Therefore, the technical problems that the survival environment of external beneficial bacteria is mutated, the beneficial bacteria can be killed simultaneously by simple bacteriostasis, the survival rate of the beneficial bacteria introduced into the vagina is low, the product is inconvenient to use and the like exist in the product for treating the vaginitis in the prior art.

Disclosure of Invention

The invention aims to solve the technical problems that the prior art has poor treatment effect of the product for treating vaginitis, cannot simultaneously exert the effects of inhibiting bacteria and promoting the growth of beneficial bacteria, and is inconvenient to use.

In order to solve the technical problems, the invention discloses a vaginal bacteriostatic preparation which comprises probiotics and a bacteriostatic composition, wherein the vaginal bacteriostatic preparation is of a multilayer structure and sequentially comprises a probiotic layer, an isolation layer and a bacteriostatic layer from inside to outside, and the mass ratio of each layer is 1:0.5-3: 0.5-6;

the probiotic layer comprises probiotics and a matrix material; 3-26 parts of probiotics and 70-97 parts of matrix material by mass;

the isolation layer comprises gelatin;

the bacteriostatic layer comprises hydrogel and a bacteriostatic composition; 47-98 parts of hydrogel and 2-55 parts of bacteriostatic composition by mass.

The vaginal bacteriostatic agent adopts a vaginal administration mode, when a user puts the vaginal bacteriostatic agent into the vagina, the bacteriostatic layer which is used as an outer layer is firstly contacted with the vaginal wall, and under the stimulation of the environment in the vagina and vaginal secretion, the hydrogel is disintegrated to release the bacteriostatic composition to inhibit harmful bacteria in the vagina; after the hydrogel is disintegrated, the gelatin of the isolating layer is degraded to form a film, so that the vaginal wall is isolated from the residual harmful bacteria in the vagina, and the vaginal wall is kept free from the continuous invasion of the harmful bacteria; after the gelatin is completely degraded, the probiotic layer is exposed, the matrix material carrying the probiotics is disintegrated, and the probiotics are released, so that harmful bacteria in the vagina are largely killed and inhibited, the growth of the probiotics is in an advantageous position, and the probiotics are continuously proliferated to further inhibit the proliferation of the harmful bacteria, so that the balance of flora in the vagina is maintained, and the ecological balance in the vagina is maintained for a long time.

Further, the probiotics are one or more of lactobacillus acidophilus, lactobacillus rhamnosus, lactobacillus plantarum and lactobacillus fermentum; the probiotics carry out normal metabolism to generate metabolites, so that the pH of the vagina is maintained at about 4.0, the reproduction of other pathogenic and harmful bacteria can be further inhibited, and the long-term balance of the flora in the vagina is promoted.

Further, the matrix material is a polymer compound or a composition thereof.

Further, the high molecular compound is one or more of gelatin, polyethylene glycol, polyvinyl alcohol, starch, cellulose and polyacrylic acid. Furthermore, the high molecular compound is gelatin, polyethylene glycol or polyvinyl alcohol, and the high molecular compound is a water-soluble high molecular material, can be dissolved at high temperature, can form gel after cooling, has a determined shape, and is convenient to prepare products with specific shapes.

Further, the isolation layer also comprises an auxiliary agent; the auxiliary agent is one or more of sucrose, maltose, lactose, fructo-oligosaccharide, cellulose, panose, protein, unsaturated fatty acid, glycerol and triglyceride. The auxiliary agent can promote the proliferation of the probiotics and can be used as a nutrient substance to further propagate the probiotics.

Further, the gelatin and the auxiliary agent are mixed according to the mass portion of 30-80 parts of gelatin and 5-35 parts of auxiliary agent.

Further, the hydrogel is aloe gel, or gelatin hydrogel, or a mixture of aloe gel and gelatin hydrogel.

Further, the antibacterial composition is at least two of A.SAP antibacterial agent, chlorhexidine acetate, octoxynol, ammonium alginate, nifuratel, nysfungin, dogwood, phellodendron, radix stemonae, wild chrysanthemum flower, Chinese violet, eucalyptus robusta, corydalis tuber, indigo naturalis, camphor, fructus cnidii, saffron, sophora flavescens, sea buckthorn seed oil, frankincense and myrrh. SAP antibacterial agent, chlorhexidine acetate, octoxynol, ammonium alginate, Nifuratel, nystatin are chemical bacteriostatic agents, the chemical bacteriostatic agent has the functions of sterilization and bacteriostasis, can quickly play a role, has quick curative effect and has the defect of easy relapse; dogwood, phellodendron, radix stemonae, wild chrysanthemum, Chinese violet, swamp mahogany, corydalis tuber, natural indigo, camphor, common cnidium fruit, saffron, lightyellow sophora root, seabuckthorn fruit oil, frankincense and myrrh are traditional Chinese medicines, decoction is obtained by a decoction method, and the decoction is concentrated and dried for use. Therefore, the invention combines the two types of bacteriostats, and can quickly and durably inhibit harmful bacteria.

The invention also claims a preparation method of the vaginal antibacterial preparation, which is characterized by comprising the following steps:

(1) taking probiotic strains, inoculating the probiotic strains in a culture medium under an aseptic condition for culture, and collecting cultured probiotic strains; dissolving the matrix material in water at 60-100 ℃, cooling to 40-55 ℃ after completely dissolving, adding probiotic bacteria and uniformly mixing to obtain a probiotic bacteria layer material;

(2) heating gelatin to melt, sterilizing the gelatin at high pressure and high temperature, and cooling to 50-60 deg.C to obtain gelatin gel as the material of the isolation layer;

(3) adding the antibacterial composition into the hydrogel, and uniformly mixing to obtain an antibacterial layer material;

(4) taking the probiotic layer material with the formula amount, adding the probiotic layer material into a mold, and cooling and molding at room temperature to obtain a probiotic layer; uniformly coating the surface of the probiotic layer with the isolating layer material according to the formula amount at the temperature of 50-60 ℃, and cooling and forming at room temperature to obtain a semi-finished product of the probiotic layer coated by the isolating layer; and finally, uniformly coating the surface of the semi-finished product with the bacteriostatic layer material according to the formula amount, pre-freezing and forming at the temperature of-5-0 ℃, further solidifying and forming at room temperature, and packaging to obtain the finished product.

The mold with different shapes is selected, the probiotic layer can be made into various shapes, such as a spherical shape, a duckbilled shape, an ellipsoidal shape, a cylindrical shape and the like, the surface of the probiotic layer is sequentially and uniformly coated with the isolation layer and the bacteriostatic layer material, and finally the obtained finished product also has a corresponding shape.

In order to avoid introducing additional impurities and pathogenic bacteria, the culture medium, gelatin, aloe gel, etc. used in the present invention, and tools used in the preparation process, including molds, coating tools, etc., are sterilized.

Compared with the prior art, the vaginal antibacterial preparation and the preparation method thereof have the following advantages:

1. the vagina bacteriostatic preparation is divided into three layers, has the functions of bacteriostasis, isolation and probiotic proliferation promotion after being placed into the vagina, has small irritation to a human body, has obvious curative effect on treating vaginitis, long duration and difficult relapse.

2. The invention combines bacteriostasis and beneficial bacterium growth promotion, maintains ecological balance of flora in vagina by a biological regulation method, has small harm to human body, thorough treatment and lasting curative effect.

3. The invention selects the bacteriostat compounded by chemical bacteriostat and Chinese medicinal bacteriostat, and can quickly and durably inhibit harmful bacteria.

4. The invention integrates the medicines with different purposes, and the user can put the product into the vagina after taking the product, thereby playing different roles and being convenient to use.

Detailed Description

The technical solution of the present invention will be described in detail by the following specific examples.