KR102709528B1 - A composition for preventing or treating vaginitis and vaginitis dryness containing lactobacillus and natural extracts - Google Patents

Abstract

The present invention relates to a composition containing lactobacillus and a natural extract for preventing or treating vaginitis and vaginal dryness, and a method for producing the same. The composition of the present invention exhibits excellent antibacterial and antifungal activity against gardnerella vaginalis and/or candida albicans, is excellent in suppressing diarrhea, itching, and peculiar odor, which are main symptoms of vaginitis, and also has excellent usability.

Description

{A COMPOSITION FOR PREVENTING OR TREATING VAGINITIS AND VAGINITIS DRYNESS CONTAINING LACTOBACILLUS AND NATURAL EXTRACTS}

The present invention relates to a composition for preventing or treating vaginitis and vaginal dryness containing lactobacillus and a natural extract, and a method for producing the same.

Under normal conditions, a woman's vagina has a slightly acidic environment due to the large number of lactic acid bacteria inside the vagina, which acts to inhibit the invasion of pathogenic microorganisms and the proliferation of fungi.

This slightly acidic environment inside the vagina can be disrupted by external factors, such as excessive vaginal washing, long-term use of antibiotics or birth control pills, or disruption of hormonal balance due to pregnancy, childbirth, or menopause, which changes the amount of lactobacilli, which are beneficial bacteria that normally exist inside the vagina. This is known to cause vaginitis, which causes discharge, itching, and pain.

Treatment of vaginitis includes sulfonamides, antibiotics, and chemically synthesized disinfectants, but the use of the above drugs is fatal not only to harmful bacteria but also to beneficial bacteria such as lactic acid bacteria, and in particular, the use of antibiotics has the inevitable problem of antibiotic resistance. In addition, in the case of chemically synthesized disinfectants (e.g. povidone-iodine), there is a concern that it may cause hypersensitivity symptoms such as iodine, itching, burning sensation, dermatitis due to mucosal damage, and hypothyroidism due to increased iodine levels.

Meanwhile, vaginal dryness is a symptom in which a woman's Y-zone becomes dry and painful. It is caused by pre- and post-menopause, childbirth and miscarriage, long-term use of birth control pills, and repeated vaginitis, and causes symptoms such as vaginal dryness, itching, and painful intercourse. In the case of vaginal dryness, the balance of the vaginal environment is disrupted, and the mucous membrane can become atrophied, which can cause vaginitis. If it occurs together with vaginitis, the pain can become severe and purulent discharge or bleeding can occur. Therefore, it is necessary to prevent or treat vaginal dryness together with vaginitis.

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Patent Publication No. 10-2178938 (2020.11.16) Patent Registration No. 10-2065934 (2020.01.14) Patent Registration No. 10-2555674 (2023.07.18) Patent Publication No. 10-2296688 (August 31, 2021)

The present inventors recognized the problems of the above-mentioned prior art and completed the present invention by demonstrating that a composition containing a specific ingredient has the effect of inhibiting the proliferation of Gardnerella vaginalis and/or Candida albicans, which are major pathogens of vaginitis, treating symptoms related to vaginitis, and also treating vaginal dryness.

The present invention comprises:

Lactobacillus plantarum fermentation lysate, Lactobacillus acidophilus fermentation lysate or a mixture thereof;

A complex extract of acai berry, elderberry and grape seed; and

The present invention relates to a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness containing a honey extract.

The present invention relates to a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness, which is prepared by a method comprising the following steps:

s1) A step of freeze-drying acai berries, elderberries, and grape seeds, respectively, and then grinding them to produce a powder form;

s2) A step of mixing the acai berry, elderberry, and grape seed powder in a weight ratio of 2:2:1;

s3) A step of adding the above mixed powder to 10 to 20 times the volume of water and making it into a slurry (suspension) state;

s4) A step of adding an enzyme mixture of cellulase, pectinase, and protease in a weight ratio of 2:2:1 to the above slurry mixture and reacting for 2-3 hours;

s5) A step of heating the above-mentioned reacted slurry mixture to 80-90 ^o C for 10-15 minutes and then cooling it;

s6) A step of filtering and concentrating the cooled mixture.

The present invention relates to a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness, wherein the pharmaceutical composition has antibacterial and antifungal activities against gardnerella vaginalis and candida albicans.

Hereinafter, this will be described in detail. All combinations of various elements disclosed in the present invention fall within the scope of the present invention. In addition, the scope of the present invention cannot be considered limited by the following specific description.

Additionally, unless otherwise defined herein, all terms used in the specification should be understood to have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

Also, singular expressions include plural expressions unless the context clearly dictates otherwise.

In this specification, the terms first, second, etc. may be used to distinguish or describe one component from another, but the components should not be construed as being limited by these terms. For example, within the scope of the present invention, the first component may be named the second component, or vice versa.

Additionally, the term "degree" combined with a number in this specification represents degrees Celsius ( ^o C) and may be used interchangeably with " ^o C" (for example, "100 degrees" is used with the same meaning as "100 ^o C").

The present invention comprises:

Lactobacillus plantarum fermentation lysate, Lactobacillus acidophilus fermentation lysate or a mixture thereof;

A complex extract of acai berry, elderberry and grape seed; and

A pharmaceutical composition for preventing or treating vaginitis and vaginal dryness containing a honey extract is provided.

In the present invention, “Lactobacillus ferment lysate” refers to a fermented lysate produced by culturing Lactobacillus spp. in a suitable medium.

In the present invention, the Lactobacillus fermentation lysate may be, for example, a fermentation lysate of Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus sakei, Lactobacillus rhamnosus GR-1, Lactobacillus fermentum, and/or Lactobacillus salivarius, preferably Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus brevis, and/or It may be a fermented lysate of Lactobacillus sakei, and more preferably, a fermented lysate of Lactobacillus plantarum and/or Lactobacillus acidophilus, but is not limited thereto.

The Lactobacillus lactic acid bacteria of the present invention is preferably, but is not limited to, a fermented lysate of Lactobacillus lactic acid bacteria isolated from a woman's vagina, breast milk, or kimchi.

In the present invention, "Acai Berry" refers to a small dark purple fruit that grows on a palm tree called Acai Palm (scientific name: Euterpe oleracea), which is native to the Amazon rainforest region of South America, particularly Brazil. The Acai Berry is known to contain anthocyanin, vitamin A, vitamin C, iron, calcium, fiber, oleic acid, linolenic acid, etc.

In the present invention, "Elderberry" refers to small dark blue or purple fruits that grow on various species of trees or shrubs belonging to the genus Elderberry (scientific name: Sambucus), which are mainly native to temperate regions of the Northern Hemisphere. The elderberry is known to contain flavonoids, anthocyanins, vitamin C, vitamin A, iron, calcium, fiber, quercetin, etc.

In the present invention, "grape seed" refers to the seed of grape fruit belonging to the grape family (scientific name: Vitis vinifera). The grape seed is rich in proanthocyanidin, polyphenol, vitamin E, linolenic acid, oleic acid, flavonoid, etc., and is known to have a strong antioxidant effect, as well as improving cardiovascular health, promoting skin health, and having an anti-inflammatory effect.

In the present invention, "extract" means a result of extraction using an appropriate extraction solvent, and the extract includes an extract obtained by extraction, a diluted or concentrated extract, a dried product obtained by drying the extract, a controlled or purified product thereof, or a fraction.

In the present invention, “composite extract” means an extract extracted through a manufacturing process in a mixture state in which each raw material is mixed simultaneously.

In the experimental examples described below, in the case of a composition containing as an active ingredient a complex extract extracted from a mixture that does not contain a specific raw material, the antibacterial and/or antifungal activity was reduced compared to a composition containing a complex extract extracted from a mixture that contains all raw materials.

It is believed that the active ingredients contained in each raw material are more easily extracted due to a synergistic effect in which the components extracted from one or more raw materials stimulate the plant cell walls of the other raw materials, thereby increasing the release of the active ingredients.

In the pharmaceutical composition of the present invention, the acai berry, elderberry, and grape seed may be used without limitation as those collected from nature, grown directly, or commercially available, and the parts used for extraction may be flowers, leaves, seeds, fruits, roots, and/or stems.

The extract of the present invention can be prepared through an extraction method commonly used in the art. For example, methods such as hot water extraction, hot water extraction, cold immersion extraction, reflux cooling extraction, ultrasonic extraction, and high-temperature pressure extraction can be used.

In preparing the extract of the present invention, water; lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propyl alcohol, and butyl alcohol; polyhydric alcohols such as glycerin, butylene glycol, and propylene glycol; hydrocarbon solvents such as chloroform, methyl acetate, ethyl acetate, benzene, hexane, diethyl ether, petroleum ether, and dichloromethane; or a mixed form thereof can be used as the extraction solvent, and water can be preferably used as the extraction solvent.

According to an embodiment of the present invention, the composite extract of acai berry, elderberry and grape seed may be prepared by a method comprising the following steps:

s1) A step of freeze-drying acai berries, elderberries, and grape seeds, respectively, and then grinding them to produce a powder form;

s2) A step of mixing the acai berry, elderberry, and grape seed powder in a weight ratio of 2:2:1;

s3) A step of adding the above mixed powder to 10 to 20 times the volume of water and making it into a slurry (suspension) state;

s4) A step of adding an enzyme mixture of cellulase, pectinase, and protease in a weight ratio of 2:2:1 to the above slurry mixture and reacting for 2-3 hours;

s5) A step of heating the above-mentioned reacted slurry mixture to 80-90 oC for 10-15 minutes and then cooling it;

s6) A step of filtering and concentrating the cooled mixture.

In the present invention, the step s1 is a step of manufacturing raw materials in powder form, and the freeze-drying and grinding can be performed using equipment generally used in the art.

In the present invention, the step s2 is a step of mixing raw materials.

In the above step s2, the acai berry, elderberry, and grape seed powders are mixed in a weight ratio of 2:2:1 and used to produce a composite extract in the subsequent step.

According to the experimental examples described below, it was confirmed that the intended effects of the present invention can be maximized when a composite extract is prepared by mixing the acai berry, elderberry, and grape seed powder in a weight ratio of 2:2:1.

In the present invention, step s3 is a preparatory step for enzyme treatment, which is a step in which water is added before the reaction to create a slurry state suitable for the enzyme reaction.

In the present invention, the water may have a volume of 10 to 20 times, and according to an embodiment of the present invention, it may have a volume of preferably 15 times, but is not limited thereto.

In the present invention, in the step s4, enzymes are added to decompose the cell walls of raw materials and increase extraction efficiency.

In the present invention, the "cellulase" is an enzyme that hydrolyzes cellulose and is mainly produced by fungi, bacteria, and protozoa, the "pectinase" is an enzyme that decomposes pectin and pectic acid, and the "protease" is an enzyme that decomposes protein.

The above enzyme may be included in an amount of 10 parts by weight based on 600 parts by weight of the total raw material, but is not limited thereto.

In the present invention, the enzyme mixture may be a mixture of cellulase, pectinase, and protease in a weight ratio of 2-1:2-1:1, preferably a mixture in a weight ratio of 2:2:1, but is not limited thereto.

Additionally, in the present invention, the enzymatic reaction may be performed for 2 to 3 hours, but is not limited thereto.

In the present invention, the step s5 is intended to inactivate the enzyme, and is performed by heating the reacted slurry mixture to 80-90 ^o C for 10-15 minutes and then cooling it.

If the above time range is exceeded, useful components contained in the extract may be destroyed, and if the above time range is less than the above time range, enzyme inactivation may be insufficient.

In addition, if the temperature range is exceeded, useful components contained in the extract may be destroyed, and if the temperature range is lower than the temperature range, enzyme inactivation may be insufficient.

In the present invention, the step s6 is a step of filtering and concentrating the mixture cooled in the step s5.

In the present invention, the concentration may be performed so that the concentration of the complex extract becomes 15 to 20% (w/v), but is not limited thereto.

In the present invention, "honey" refers to a viscous sweetener that honeybees (mainly of the genus Apis) consume from the nectar glands of flowers, and then decompose, accumulate, and concentrate through enzymatic action in their bodies and store in their honeycombs. The honey contains glucose, fructose, minerals, vitamins, amino acids, antioxidants, etc., and is known to be used not only as a natural sweetener, but also to have health and beauty effects such as antibacterial, anti-inflammatory, and moisturizing.

In the present invention, the honey extract may be prepared by a method comprising the following steps:

h1) Step of mixing honey and water in a volume ratio of 1:1 and heating; and

h2) A step of filtering the heated mixture.

In the above h1 step, heating can be performed to a temperature of 50 to 60 ^o C, and the h1 step can be performed for 3 to 4 hours while maintaining the temperature, but is not limited thereto.

In the present invention, the filtration can be performed through a method commonly known in the art, and can be performed using, for example, a filter paper.

According to an embodiment of the present invention, the honey extract may be concentrated to have a final concentration of 40 to 42 brix, but is not limited thereto.

The contents of the Lactobacillus plantarum fermentation lysate, Lactobacillus acidophilus fermentation lysate or a mixture thereof; the composite extract of acai berry, elderberry and grape seed; and the honey extract included in the composition of the present invention can be appropriately determined in consideration of various factors, such as the purpose of use, period of use, type of formulation, route of administration, condition of the site to be administered, etc.

According to an embodiment of the present invention, the content of the Lactobacillus plantarum fermentation lysate, the Lactobacillus acidophilus fermentation lysate or a mixture thereof; the composite extract of acai berry, elderberry and grape seed; and the honey extract may be 0.001 to 20 wt% based on the total weight of the composition, and preferably 0.001 to 10 wt%. According to an embodiment of the present invention, it may be 0.001 to 1 wt% based on the total weight of the composition, but is not limited thereto.

The composition of the present invention may be a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness, having antibacterial and/or antifungal activity against gardnerella vaginalis and/or candida albicans. The composition of the present invention helps restore the level of lactic acid bacteria, which are beneficial bacteria in the vagina, to a normal range, and helps restore a slightly acidic environment of pH 3.8 to 4.5 by lowering the pH in the vagina.

The composition of the present invention can be manufactured in the form of general emulsified formulations and solubilized formulations using conventionally known manufacturing methods. For example, it can be manufactured in various formulations such as tablets for vaginal insertion, ointments, gels, creams, cleansers, sprays, water (W) type, oil (O) type, oil-in-water (O/W) type, water-in-oil (W/O) type, silicone (S) type, water-in-silicon (W/S) type, silicone-in-water (S/W) type, solid, and liquid.

The composition of the present invention may further include pharmaceutically acceptable additives. The pharmaceutically acceptable additives of the present invention may include, but are not limited to, binders, thickeners, anti-adhesives, plasticizers, surfactants, stabilizers, disintegrants, excipients, conditioning agents, neutralizers, pigments, fragrances, etc. The content and type of the additives may be appropriately selected by a person skilled in the art within a range known to those skilled in the art, within a range that does not affect the stability or efficacy of the active ingredient.

According to another aspect of the present invention, a feminine hygiene composition comprising the pharmaceutical composition is provided. The pharmaceutical composition is as described above, and is omitted to avoid excessive repetition of the same content in the specification.

In the present invention, the feminine hygiene product may be a cleansing agent, a cosmetic agent, or a wet tissue agent. For example, the cleansing agent agent may be formulated as a spray, liquid, gel, or foam type, and the cosmetic agent agent may be formulated as a lotion, toner, cream, essence, powder, aerosol, oil, or mist.

Another aspect of the present invention provides a method for preparing a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness.

In this specification, the specific details of the manufacturing method are substantially the same as those described in the composition, and are omitted to avoid repetition of the same details.

The pharmaceutical composition for preventing or treating vaginitis and vaginal dryness of the present invention exhibits excellent antibacterial and antifungal activity against gardnerella vaginalis and/or candida albicans, is excellent in suppressing the main symptoms of vaginitis, such as diarrhea, itching, and peculiar odor, and also has excellent usability.

In addition, since the extract of the present invention uses natural materials as raw materials, there is a low possibility of side effects, such as carcinogenicity, occurring due to chemical synthetic ingredients.

In addition, according to the method for producing a complex natural extract of the present invention, since the use of an organic solvent is excluded in the extraction process, no side effects occur due to the use of an organic solvent.

Therefore, the composition according to the present invention is excellent in usefulness as a composition for preventing or treating vaginitis and vaginal dryness.

The effects that can be obtained from the examples are not limited to the effects mentioned above, and other effects that are not mentioned can be clearly derived and understood by a person having ordinary skill in the art based on the detailed description below.

Hereinafter, the present invention will be described in more detail by way of examples. However, these examples are intended to exemplify the present invention, and the scope of the present invention is not limited by these examples. In addition, each component or feature may be considered optional unless otherwise explicitly stated. Each component or feature may be implemented in a form that is not combined with other components or features. In addition, various embodiments may be configured by combining some components and/or features. Some components or features of one embodiment may be included in another embodiment, or may be replaced with corresponding components or features of another embodiment. In addition, terms not specifically defined in this specification should be understood to have the meaning commonly used in the technical field to which the present invention belongs.

Manufacturing Example 1. Manufacturing of Lactobacillus Ferment Lysate

Lactobacillus plantarum and Lactobacillus acidophilus were cultured in liquid MRS broth medium at 37 ^o C and 5% _CO2 for 3 days, respectively.

Centrifuge the above cultured lactic acid bacteria at 15,000 rpm and wash 2-3 times with PBS to remove residual medium components.

Lactobacillus plantarum and Lactobacillus acidophilus fermentation lysates were obtained by sonication at 4 ^o C for 2 hours.

Thereafter, the obtained Lactobacillus plantarum fermentation lysate and Lactobacillus acidophilus fermentation lysate are mixed at a weight ratio of 1:1 to obtain a Lactobacillus fermentation lysate.

Manufacturing Example 2. Manufacturing of a combination extract of acai berry, elderberry, and grape seed

Acai berries, elderberries, and grape seeds are each freeze-dried and then ground into powder using a fine grinder.

Mix the above acai berry, elderberry, and grape seed powder in a weight ratio of 2:2:1.

Add the above mixed powder to 15 times the volume of water, stir to make a slurry (suspension), measure the pH, and adjust to pH 5.0 and the temperature 40 ^o C.

Cellulase, pectinase, and protease are mixed in a weight ratio of 2:2:1, and 10 parts by weight are added relative to 600 parts by weight of the slurry mixture, and reacted for 2-3 hours.

Heat to 80-90 ^o C, maintain for 10-15 minutes, then cool quickly.

Filter to remove solids, and concentrate under vacuum to a concentration of 15-20% (w/v).

Manufacturing Example 3. Honey Extract

Mix honey and water in a 1:1 ratio, heat slowly over low heat to 50-60 degrees, and keep for 3-4 hours.

A honey extract of about 40-42 brix is produced by removing impurities and honey residue through a filter.

Example

The above-mentioned manufactured Lactobacillus fermentation lysate, composite extract, and honey extract were mixed in a weight ratio of 1:3:1 to prepare a sample of the example.

Comparative Example 1

A sample of Comparative Example 1 was prepared by including only the Lactobacillus fermentation lysate prepared above.

Comparative Example 2

In the preparation of the composite extract of the above Preparation Example 2, the composite extract was prepared in substantially the same manner as in Preparation Example 2, except that the acai berry, elderberry, and grape seed powders were mixed in a weight ratio of 1:1:1, and the prepared Lactobacillus fermentation lysate, composite extract, and honey extract were mixed in a weight ratio of 1:3:1 to prepare a sample of Comparative Example 2.

Experimental Example 1. Evaluation of antibacterial and antifungal activity by disk diffusion method

Antibacterial and antifungal activity against Candida albicans and Gardnerella vaginalis, the causative agents of vaginitis, was determined using the disc diffusion method using paper discs.

Specifically, pre-cultured Gardnerella vaginalis and Candida albicans were each dispensed into a medium (Sabouraud dextrose agar difco. USA) using a platinum skewer, streaked, and left for 5 minutes. Thereafter, paper discs on which the samples of the above examples and comparative examples were each spotted at the same concentration were placed on the medium. In the evaluation of the antibacterial activity against Gardnerella vaginalis, as a control group, metronidazole was spotted at a concentration of 50 μg/disc on a paper disc and placed on the medium, and in the evaluation of the antifungal activity against Candida albicans, as a control group, itraconazole was spotted at a concentration of 50 μg/disc on a paper disc and placed on the medium. Thereafter, the medium on which the discs were placed was cultured in an incubator at 37 ^o C for 24 hours, and the size of the inhibition zone was measured. The results are shown in the table below.

Size of the restraint ring (mm) Gardnerella vaginalis Candida albicans Control group 16 15 Example 25 21 Comparative Example 1 14 12 Comparative Example 2 21 18

As shown in the table above, it can be confirmed that the composition of the example has a similar or greater inhibitory activity against Candida albicans and Gardnerella vaginalis than the comparative example and the control group, so it can be confirmed that the composition of the present invention can be usefully used for the prevention or treatment of vaginitis.

Experimental Example 2. Evaluation of efficacy in suppressing diarrhea, itching, and specific odor

In order to confirm the inhibitory effect and usability (overall satisfaction including cleanliness, freshness, and moisturizing sensation) of the composition of the present invention on the main symptoms of vaginitis, such as diarrhea, itching, and peculiar odor, an experiment was conducted on 20 volunteers (regardless of age) who had the above symptoms and had experience using vaginitis treatments currently available on the market.

Specifically, 20 applicants were administered approximately 10 mL of the preparation manufactured according to the ingredients and contents shown in the table below once a day via a syringe into the vagina for 4 weeks according to the guide, and then evaluated according to a 5-point rating system.

ingredient Content (weight%) Example 0.005 Repair control 0.05 Lactic acid 0.05 Hydroxyethylcellulose 0.70 Sodium polyglutamate 0.01 Sodium Hyaluronate 0.001 Disodium edetate hydrate 0.03 Sodium citrate dihydrate 0.01 Methyl p-hydroxybenzoate 0.20 Sodium polyacrylate 0.13 purified water Remaining amount

The evaluation criteria were set to 3 points for the previously used vaginitis treatment, and the relative scores were evaluated as very good (5 points), good (4 points), average (3 points), poor (2 points), and ineffective (1 point), and the results are shown in the table below.

Great haemorrhage A sense of accomplishment Special feature Feel of use 5 points 11 people 12 people 9 people 6 people 4 points 8 people 8 people 8 people 11 people 3 points 1 person 1 person 3 people 3 people 2 points - - - - 1 point - - - - average 4.5 4.75 4.3 4.15

As shown in the table above, the average values for each evaluation item were 4.5 points for suppression of diarrhea, 4.75 points for suppression of itching, and 4.3 points for suppression of peculiar odor, all of which received positive evaluations above good. The usability, which is an evaluation of overall satisfaction such as cleanliness, freshness, and moisturizing feeling after use, also received an average of 4.15 points, confirming excellent usability.

In addition, no special side effects related to the administration of the gel during the experimental period were reported among the applicants, confirming that the composition of the present invention has excellent stability.

The various embodiments described above may be embodied in other specific forms without departing from the technical idea and essential characteristics thereof. Therefore, the detailed description above should not be construed as limiting in all aspects but should be considered as illustrative. The scope of the various embodiments should be determined by a reasonable interpretation of the appended claims, and all changes within the equivalent scope of the various embodiments are included in the scope of the various embodiments. In addition, claims that do not have an explicit citation relationship in the patent claims may be combined to form an embodiment or included as a new claim by post-application amendment.

Claims (3)

Lactobacillus plantarum fermentation lysate, Lactobacillus acidophilus fermentation lysate or a mixture thereof;
A complex extract of acai berry, elderberry and grape seed; and
Contains honey extract,
The above complex extract of acai berry, elderberry and grape seed
s1) A step of freeze-drying acai berries, elderberries, and grape seeds, respectively, and then grinding them to produce a powder form;
s2) A step of preparing a mixed powder by mixing the acai berry, elderberry, and grape seed powder in a weight ratio of 2:2:1;
s3) A step of adding the above mixed powder to 15 times the volume of water and making it into a slurry (suspension) state;
s4) A step of adding an enzyme mixture of cellulase, pectinase, and protease in a weight ratio of 2:2:1 to the above slurry mixture and reacting for 2-3 hours;
s5) A step of heating the above-mentioned reacted slurry mixture to 80-90 ^o C for 10-15 minutes and then cooling it;
s6) is manufactured by a method including the step of filtering and concentrating the cooled mixture;
The above honey extract
h1) Step of mixing honey and water in a volume ratio of 1:1 and heating; and
h2) a step of filtering the heated mixture; manufactured by a method including:
A pharmaceutical composition for preventing or treating vaginitis and vaginal dryness, wherein the above Lactobacillus plantarum ferment lysate, Lactobacillus acidophilus ferment lysate or a mixture thereof; a complex extract of acai berry, elderberry and grape seed; and a honey extract are mixed in a weight ratio of 1:3:1.
delete In the first paragraph,
The pharmaceutical composition above is a pharmaceutical composition for preventing or treating vaginitis and vaginal dryness, having antibacterial and antifungal activities against gardnerella vaginalis and candida albicans.