[invention Title]

AGENT FOR THE TREATMENT OF VAGINITIS CONTAINING MANDELIC ACID AS AN ACTIVE INGREDIENT

[Technical Field]

The present invention relates to an agent for treatment of vaginitis comprising mandelic acid as an active ingredient.

[Background Art]

Lactobacillus species (spp.), inhibiting the human oral cavity, digestive tract, genitourinary tract as a normal flora (Elmer et al. 1996, Pavlova et al. 1997), residing in the female vaginal canal as a dominant flora produce growth inhibitors of a variety of pathogenic microorganisms to minimize opportunistic infections, produce various kinds of organic acids, hydrogen peroxide, bacteriocin, etc. to inhibit the growth of pathogens and obstruct the adhesion of pathogens in the intestines, thus maintaining the stability and balance of the ecosystem

(Salminen, S. et al. 1996). Lactobacillus species take nutrition by converting glycogen into lactic acid. Here,

the lactic acid that is a metabolic product maintains the proper acidity in the vaginal canal and acidifies pH to neutralize pathogenic bacteria. Hydrogen peroxide produced induces oxidation for cells and destroys protein structure, thus resulting in extinction of pathogenic bacteria.

In the vaginal canal that is strong acid, a variety of bacteria reside alike the large and small intestines and the majority of the bacteria are lactobacillus species as normal flora. The vaginal canal before adolescence is kept at pH 6-8, acidities similar to the skin; however, at early adolescence when the secretion of female sex hormone starts, the growth of vaginal epithelial cells and the accumulation of glycogen in cells start together with physical changes and glycogen is converted into lactic acid by enzymes produced from cells or bacteria. As a result, pH in the vaginal canal becomes strong acid not exceeding 4.5. However, if bacterial vaginitis is caused, the number of lactobacillus species, a dominant flora, is decreased and gardenerella vaginalis, an anaerobic organism, is increased, which causes bad odors in the secretion and an increase in pH.

The cause of vaginitis is varied such as an infection of bacteria or viruses, antibiotic usage, contraceptive

preparations, excessive vaginal detergent, etc. Moreover, there are several common types of vaginitis: first, it is bacterial vaginitis caused by an excessive propagation of minor pathogens in the vaginal canal according as the weak acid environment of vaginal canal is destroyed by various factors. The main symptoms of vaginitis include an abnormal vaginal discharge to the extent that it may wet underwear with a fish-like odor and itching. Discomfort during urination or sexual intercourse may also occur. Next, the most common vaginitis is Candida vaginitis caused by a yeast infection that may occur when the vaginal environment is out of balance according as the resistance of the body is decreased. The main symptoms produced by the Candida vaginitis are vaginal and/or vulvar itching (pruritus) , or even a vulvar burning sensation. There is a cheese-like (caseous) white to white yellow discharge. Also there can be swelling of the perineum or erythema.

Finally, the other common vaginitis is trichomonas vaginitis caused by a tiny single-celled anaerobic parasite known as a trichomonas. When trichomonias transmitted through sexual intercourse enters into the vagina, it can inhabit the urethra and bladder, thus

causing cystitis and pelvic inflammatory disease. Trichomonas vaginitis multiplied through sexual intercourses with new and multiple sex partners reaches 15 to 20% out of the whole vaginitis cases (Katherine et al. 2003) . A trichomonas infection produces a thin, frothy, and greenish to yellowish vaginal discharge which may have a bad or foul-smelling odor. This infection can irritate the vagina causing swelling, burning or itching of the vaginal opening and even the labia. Accordingly, various methods for preventing and treating the vaginitis have been studied and the general methods include an oral administration of agent for the treatment of vaginitis such as metronidazole and a usage of antibiotics of cream type. However, the antibiotics usage may remove the lactobacillus species, a normal flora, which results in the relapse of vaginitis to cause a chronic disease.

Meanwhile, mandelic acid (MA) , an alpha hydroxyl acid (AHA) produced naturally, is an enriched organic acid derived from the hydrolysis of an extract of almonds. Mandelic acid is used for treatment of diseases and wounds related to skins and has no toxicity for cells. Mandelic acid having an antibiosis inhibits the growth of

propionibacterium acnes. Particularly, alpha hydroxyl groups contained in mandelic acid maintain skin' s moisture that may be vaporized due to skin aging and prevent skin pigmentation disorders, not stimulating the skin. Moreover, mandelic acid dissolved in urine at a concentration of 30

to 50 g/ & shows an inhibitory effect for pathogens such as herpesvirus (HIV) types 1 and 2 or neisseria gonorrhoeae, has antibiotic activities for both Gram-positive bacteria and Gram-negative bacteria, has no mutagenic factors in in-vitro experiments and has a low acute toxicity "(Lourens et al. 2002) . In addition, mandelic acid is used for an analytical material for determining an infection through host cell or sperms or for an analytical reagent as an intermediate product of pharmaceutical preparations.

Accordingly, the inventors of the present invention have conducted researches in materials for inhibiting the growth of pathogens that cause vaginitis, not affecting lactobacillus species, a normal flora, in the vaginal canal and confirmed that mandelic acid is effectively used as an agent for treatment of vaginitis, which does not inhibit the growth of lactobacillus species but shows excellent antibiotic activities for pathogens, thus

completing the present invention.

[Disclosure]

[Technical Problem] An object of the present invention is to provide an agent for treatment of vaginitis comprising mandelic acid as an active ingredient.

[Technical Solution] To accomplish the object of the present invention, there is provided an agent for treatment of vaginitis comprising mandelic acid expressed by chemical formula 1 below.

[Chemical Formula 1]

[Description of Drawings]

Fig. 1 shows the results of growth inhibitory effects of mandelic acid for selection of strains on normal and

pathogenic bacteria in the vaginal canal;

Fig. 2 is colony photographs showing the results of spray tests of mandelic acid in accordance with the present invention; Fig. 3 is a graph depicting the result of spray tests of mandelic acid in accordance with the present invention;

Fig. 4 is colony photographs illustrating the results of a selective growth inhibitory effect of mandelic acid in accordance with the present invention on normal and pathogenic bacteria;

Fig. 5 is a graph depicting effects of mandelic acid in accordance with the present invention on the respective growth phases of Lactobacillus fermentum MS79;

Tig, 6 is .a graph depicting effects of mandelic acid in accordance with the present invention on the respective growth phases of Escherichia coli 0157 :H7;

Fig. 7 is a graph depicting effects of mandelic acid in accordance with the present invention on the respective growth phases of Staphylococcus aureus KCCM 40881; and Fig. 8 shows morphological changes of strains after processing mandelic acid.

[BEST MODE]

The present invention provides an agent for treatment of vaginitis comprising mandelic acid expressed by chemical formula 1 below. [Chemical Formula 1]

As a result of conducting spray test, paper test and paper disc test for lactobacillus species, a normal flora, in vaginal canal and pathogens that may cause vaginitis, it can be learned that mandelic acid does not exert influence on the growth of lactobacillus species but shows the growth inhibitory effect on pathogens, such as Bacillus cereus ATCC 49063, Enterococcus faecalis, Escherichia coli O157:H7, Listeria monocytogenes KCTC 3710, Salmonella enteritidis, Salmonella gallinarum, Shigella sonnei ATCC 9290, Yersinia enterocolitica ATCC 23715, Pseudomonas aeruginosa KCTC 1636 and Staphylococcus aureus KCCM 40881.

Moreover, mandelic acid does not exert considerable

influence on Lactobacillus species in all growth phases such as lag phase, exponential (log or logarithmic) phase and stationary phase. However, in case of pathogens cultured in media added with mandelic acid, the viable count is decreased in the exponential and stationary phases much more than that of pathogens cultured in general media, to which mandelic acid is not added.

In addition, comparing the surfaces of cells cultured in mandelic acid-added media with those of cells cultured in general media via a scanning electron microscope (SEM) , it can be observed that lactobacillus species is not influenced considerably by mandelic acid; however, the cell surfaces of pathogens are not smooth and round but hollowed with large .holes here and there . Accordingly, the mandelic acid of formula 1 decreasing the viability rate of pathogens, not affecting the growth of lactobacillus species, a normal flora, can be effectively used as an agent for treatment of chronic vaginitis.

The agent for the treatment of vaginitis of the present invention may be a pharmaceutical composition and comprise at least one active ingredient showing the same

efficacy as the mandelic acid additionally.

The agent for the treatment of vaginitis of the present invention may be used in the form of general medical formulations. That is, the mandelic acid of formula 1 can be administrated to patients in various forms, such as oral and parenteral administrations, in actual clinical administrations. In case of formulation, the mandelic acid of formula 1 of the present invention may be formulated into various dosage forms using commonly used diluents or excipients such as fillers, expanders, bonding agents, humectants, disintegrants, surfactants, etc. Solid dosages for oral administration include tablets, pillets, powders, granules, .capsules, etc.. Such solid dosages are prepared by admixing the mandelic acid of formula 1 with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple expedients, lubricants such as magnesium styrate, talc, etc. may be added. Liquid dosage forms for oral administration, such as suspensions, internal solutions, emulsions, syrups, etc., may comprise simple diluents, such as water and liquid paraffin, as well as various excipients, such as humectants, sweeteners, aromatics, preservatives, etc.

Dosage forms for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized agents, suppositories, creams, ointments, jellies, foams, detergents and vaginal inserts. Non-aqueous solvents and suspensions may be prepared using vegetable oils, such as propylene glycol and polyethylene glycol, olive oil, or using injectable esters such as ethyloleate. As bases for suppositories, witepsol, macrogol, Tween 61, cacao oil, laurinic acid, and glycerogelatine are useful. Moreover, calcium or vitamin D3 may be added thereto for promoting efficacy of the treatment of vaginitis.

The dosages of the agent for the treatment of vaginitis of the present invention may be varied according to various relevant factors, such as weight, age, sex, health status, diet and excretion rate of patients, time and method of administration, and severity of symptoms. In general, it is preferable to administrate such drugs in a total dosage of 0.01 to 1,000 mg on the basis of the amount of mandelic acid once or several times a day to adults .

The agent for the treatment of vaginitis of the present invention may be used by itself or in combination

with operations, radiation therapies, hormone therapies, chemical therapies and methods using biological response modifiers .

[MODE FOR INVENTION]

Hereinafter, the present invention will now be described more fully with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention .to those skilled in the art.

Example 1: Measurement of Growth Inhibitory Effects of Mandelic Acid of Formula 1 on Microorganisms in Vaginal Canal

1-1: Isolation and Culture of Strains In this experiment, strains were isolated and cultured in order to verify the growth inhibitory effects of mandelic acid on microorganisms in the vaginal canal. Here, the mandelic acid of reagent degree sold

commercially was used.

For the isolation of strains, 105 lactobacillus species isolated from the vaginal canals of health Korean

women were inoculated 1% respectively into 5 m# MRS media and cultured at 37 ^° C for 12 hours. As pathogens, Bacillus cereus ATCC 49063, Enterococcus faecalis, Escherichia coli

0157 :H7, Listeria monocytogenes KCTC 3710, Salmonella enteritidis, Salmonella gallinarum, Shigella sonnei ATCC

9290, Yersinia enterocolitica ATCC 23715 were cultured in LB media, Pseudomonas aeruginosa KCTC 1636 were stirred at

200 rpm to be cultured in modified media at 37 ^° C and Staphylococcus aureus KCCM 40881 were stirred at 200 rpm

to be cultured in TSB media at 37 ^° C . The compositions of the media applied to the respective strain cultures were depicted in Tables 1 and 2.

[Table 1]

[Table 2 ]

1-2: Selection of Strains

Minimal inhibitory concentrations (MIC) to

benzalkonium chloride (BKC) for the strains isolated and cultured in Example 1-1 were measured. After the measurement, six strains of high MIC to BKC were selected and minimal inhibitory concentrations to mandelic acid were measured using microtiter plates via National Committee for Clinical Laboratory Standards (NCCLS) for these strains.

After culturing lactobacillus species and pathogens in 5 m£ broths at 37 ^° C under the anaerobic condition for 12 hours, the resulting broths were moved to a microcentrifuge tube and centrifuged to remove

supernatants. To remove the media ingredients used, 1 m# of 85% saline was added thereto to be completely elutriated and then were centrifuged repeatedly for 5 minutes to remove supernatants again. Precipitated cell

pellets were added with 1 m£ of 85% saline to be elutriated. Subsequently, the resulting cell pellets were inoculated 10% into microtiter plates so that the optical density at 625 nm (0.D625) became 0.09, where colony forming unit (CFU) became 107, using MacFarland method. Concentration range of mandelic acid was regulated from 155 βg/ϊ&l to 10 mg/m# to be processed to the strains. After culturing at 37 ^° C for 24 hours, the optical density at 600 nm (0.D600)

was measured using a spectrophotometer (Molecular Devices, VERSAmax microplate reader, USA) .

The experiment results were depicted in Fig. 1. As shown in the figure, it was confirmed that the mandelic acid did not have an effect on the growth of lactobacillus

species in the concentration not exceeding 5 mg/m-β, since the mandelic acid did not show the growth inhibitory effect on lactobacillus species, the normal flora, even at

5 mg/ffl^. However, the mandelic acid of low concentration showed considerable growth inhibitions in pathogens such as Enterococcus faecalis, Yersinia enterocolitica ATCC

23715, Shigella sonnei ATCC 9290, Listeria monocytogenes

KCTC 3710. Moreover, in cases of Escherichia coli 0157 :H7,

Salmonella .enteritidis ...and Salmonella gallinarum.,,. the minimal inhibitory concentration (MIC) to mandelic acid

was shown at 2.5 nag/ml, a higher concentration than the other pathogens .

Accordingly, it could be understood that the mandelic acid of low concentration inhibited the growth of the pathogens that might cause vaginitis, not influencing the growth of normal bacteria.

Example 2: Spray Test for Mandelic Acid of Formula 1

The following spray test was carried out in order to verify the growth inhibitory effects of mandelic acid on normal and pathogenic bacteria.

Each 200 μ£ of lactobacillus and pathogens including Staphylococcus aureus KCCM 40881 and Escherichia coli

0157 :H7, diluted until the CFU became 107, was spread on

MRS agar media (1.5% agar) and LB agar media (1.5% agar) of culture plates and dried for 3 minutes. Then, mandelic acid solutions prepared to have mandelic acid concentrations of 0.5 M and I M (1 M of NaCl, 50% EtOH, pH

5.0) were sprayed to the plates in an amount of 100 id twice and dried for 3 minutes. The dried plates were cultured at 37 ^° C for 24 hours and colonies were counted. Here, , a group, to .which . only 50% EtOH was processed, was used as a control group.

The results were depicted in Figs. 2 and 3.

As shown in Fig. 2, the colonies of lactobacillus species were observed in 1 M of mandelic acid, however, the colonies of Staphylococcus aureus KCCM 40881 and Escherichia coli 0157 :H7 were not seen in the mandelic acid of 0.5.

Moreover, as shown in Fig. 3, where the results of Fig. 2 were depicted with a bar graph showing the

viability rate (%) of the respective strains according to the mandelic acid concentrations of 0.5 M and 1 M, it was seen that the viability rate of Staphylococcus aureus KCCM 40881 and Escherichia coli 0157 :H7 was remarkably decreased compared with lactobacillus species. That is, it was learned that the viability rate of lactobacillus in the mandelic acid of 0.5 M was higher about 6 times than that of Staphylococcus aureus KCCM 40881 and in the mandelic acid of 1 M it was higher about 15 times. Accordingly, it could be understood in this experiment that the mandelic acid showed high growth inhibitory effects on the pathogens, not affecting the growth of normal bacteria, the same as the results of Example 1.

Example 3: Paper Disc Test for Mandelic Acid of Formula 1

The following paper disc test was carried out in order to verify a selective inhibitory effect of mandelic acid on normal and pathogenic bacteria.

Each 10 ml of 0.7% soft agar of LB, MRS and TSB media containing 106-107 CFϋ/m£ of lactobacillus and pathogens including Escherichia coli 0157 :H7, Listeria monocytogenes

KCTC 3710 and Staphylococcus aureus KCCM 40881 was covered

evenly and hardened. Subsequently, paper discs (φ 6mm, Advantec Co., USA) were arranged thereon and the mandelic acid was dropped by concentrations, referring to direct and deferred techniques. Nest, the plates were cultured at

37 ^° C for 12 hours and the antimicrobial activities were confirmed with the existence and size of clear zones. The results were depicted in Fig. 4. As shown in the figure, the clear zones for all pathogens were shown most large in the mandelic acid of 1

M and the average size of the clear zones was 2 to 3 cm. It was learned that lactobacillus showing few clear zones had an excellent resistance to the mandelic acid, compared with, the .pathogens.. Accordingly, it could be understood from this experiment that the mandelic acid had the selective inhibitory effect inhibiting the growth of pathogens only and it inhibited concentration-dependentIy up to 1 M.

Example 4: Measurement of Effects of Mandelic Acid of Formula 1 on the Growth Phases of Strains

To examine the selective inhibitory effect of mandelic acid according to growth phases of lactobacillus

and pathogens, the experiment was carried out by dividing the growth phases of strains roughly into lag phase, exponential phase and stationary phase, to which mandelic acid was processed. A control group, lag phase group, exponential phase group and stationary phase group were prepared by inoculating 1% of lactobacillus and pathogens in general liquid media (MRS and LB, pH 5.0) . Here, to compare the selective inhibitory effects according to the respective growth phases, each 1% of lactobacillus and pathogens was inoculated in the general liquid media (MRS and LB, pH 5.0) for the control group and then the viable counts were measured at two-hour intervals for the first 24 hours to depict growth carves. For the lag phase group, each 1% of lactobacillus and pathogens was inoculated in media where 1 M of NaCl was added to the general liquid media (MRS and LB, pH 5.0) and in media where 1 M NaCl and 10 mM of mandelic acid were added to the general liquid media (MRS and LB, pH 5.0) and the viable counts were measured after lapses of 0, 4 and 12 hours. Moreover, for the exponential phase and stationary phase groups, strains obtained by centrifuging lactobacillus and pathogens cultured in the general liquid media at 15,000 rpm for 5 minutes were

elutriated and cultured in media where 1 M of NaCl was added to general liquid media (MRS and LB, pH 5.0) and in the media where 1 M of NaCl and 10 mM of mandelic acid were added to the general liquid media (MRS and LB, pH 5.0). Subsequently, the viable counts in the exponential phase group were measured after lapses of 4, 8, 16 hours and those in the stationary phase group were measured after lapses of 10, 14 and 22 hours, respectively.

The results of the measurement were depicted with growth curves in Figs. 5 to 7.

As shown in Fig. 5, in case of lactobacillus cultured in MRS media, the viable counts of the media where only NaCl was added and those of the media where NaCl and mandelic acid wexe added were all fixed in the lag, exponential and stationary phases.

On the other hand, as shown in Figs. 6 and 7, in cases where Escherichia coli 0157 :H7 and Staphylococcus aureus KCCM 40881 were cultured in LB media, the viable counts of the media where only NaCl was added and those of the media where NaCl and mandelic acid were added were distinguished from each other in the exponential stationary phases. Moreover, it was seen that the viable counts of the two strains were noticeably decreased in the

exponential phase group.

In case of Escherichia coli 0157 :H7, when cultured in the media where NaCl and mandelic acid were mixed, the viable counts in the exponential phase were decreased 104 times after 4 hours and 105 times after 8 hours compared with the general media. Moreover, in the stationary phase, when cultured in the media where NaCl and mandelic acid were mixed, the viable counts were decreased 102 times after 12 hours than those of the media where only NaCl was added, 102 time after 4 hours and 104 times after 12 hours than those of the general media.

In case of Staphylococcus aureus KCCM 40881, when cultured in the media where only NaCl was added, the viable counts in the .exponential phase were decreased 10 times after 4 hours and 102 times after 8 hours than those of the general media. Moreover, in the stationary phase, when cultured in the media where NaCl and mandelic acid were mixed, the viable counts were decreased 102 times after 4 hours and 103 times after 8 hours than those of the general media, and also decreased 102 times after 12 hours than those of the media where only NaCl was added.

In addition, it was seen that there were differences of the viable counts in lag, exponential and stationary

phases between pathogens as well as between lactobacillus and pathogens. In the lag phase, the viable counts of lactobacillus, Escherichia coli 0157 :H7 and Staphylococcus aureus KCCM 40881 were shown nearly fixed. However, in case of Escherichia coli 0157 :H7, the viable counts were decreased 10 times after 12 hours from the lag phase and decreased more than 103 times in the exponential and stationary phases. In case of Staphylococcus aureus KCCM 40881, the viable counts were fixed after 12 hours from the lag phase and decreased more than 102 times in the exponential and stationary phases. Like this, the growth inhibitory degrees according to the growth curves for the three strains were shown distinguished from one another and it was seen that the growth of lactobacillus was not affected by the mandelic acid in the lag, exponential and stationary phases. On the other hand, it could be observed that the growths of the pathogens were considerably affected by the mandelic acid and, particularly, those in the exponential and stationary phases were influence by the mandelic acid much more than in the lag phase.

Example 5: Measurement of Morphological Changes of Strains After Processed with Mandelic Acid of Formula 1

Morphological changes were observed using a scanning electron microscopy (SEM) in order to examine the degree of inhibitory effects of mandelic acid according to strains and growth phases. Media where 1 M of NaCl, pH 5.0, and 10 mM of mandelic acid were mixed were compared with cells cultured in general media (MRS and LB) as a control group. After collecting strains in the lag phase centrifuged at 15,000 rpm for 5 minutes, the strains were washed and elutriated

with phosphate buffer of pH 8.0 twice. Subsequently, 5 μi of strain suspension was dropped to be spread thinly and dried at room temperature for 1 hour. After a fixing process for 3 to 4 hours, a dewatering process was added thereto .at ten-minute intervals and a natural dry followed. Next, the surfaces were pre-treated to observe using a field emission scanning electron microscopy (FE-SEM, Hitach S-4200) under the condition of 7.0kv * 10.0k. The results were depicted in Fig. 8. As shown in the figure, it was seen that the cell surfaces of Lactobacillus fermentum MS79, Staphylococcus aureus KCCM 40881 and Escherichia coli 0157 :H7 cultured in the general media (MRS and LB) did not get damaged as smooth and round as observed. On the other hand, it was

observed that the cell surfaces of Staphylococcus aureus KCCM 40881 and Escherichia coli 0157 :H7 cultured in the media mixed with 1 M NaCl and 10 mM mandelic acid were roughly damaged as they were not smooth and round but hollowed with large holes here and there. Compared with the cells cultured in the general media, lactobacillus fermentum MS79 cultured in the media mixed with 1 M NaCl and 10 mM mandelic acid, it was seen that the lengths were extended slightly than those of control group under the influence of mandelic acid and the cell surfaces were hollowed and not smooth under the influence of NaCl. However, it was observed that lactobacillus fermentum MS79 cultured in the media mixed with 1 M NaCl and 10 mM mandelic acid underwent few influences on the whole, compared with Staphylococcus aureus KCCM 40881 and Escherichia coli 0157 :H7.

Accordingly, it could be confirmed through the observation of the cell surfaces that the mandelic acid showed the effects of decreasing the viability rate of pathogenic bacteria rather than the normal bacteria.

Preparation examples for the compositions of the present invention will now be illustrated as follows.

Preparation Example 1: Preparation of Powder Mandelic acid of formula 12 g

Lactose 1 g The above ingredients were mixed and put into an airtight bag to prepare a powder.

Preparation Example 2: Preparation of Tablet Mandelic acid of formula 1 100 mg Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

The above ingredients were mixed to prepare a tablet according to an ordinary method for preparing tablets.

Preparation Example 3: Preparation of Capsule Mandelic acid of formula 1 100 mg

Corn starch 100 mg

Lactose 100 mg Magnesium stearate 2 mg

The above ingredients were mixed and put into a gelatin capsule to prepare a capsule according to an ordinary method for preparing capsules.

Preparation Example 4: Preparation of Lipid-Soluble Ointment (W/0 Formulation) [Table 3]

During the preparation of ointment, the ingredients except for carboxylvinylpolymer and kojic acid were emulsified at above 60 ^° C and stirred by adding carboxylvinylpolymer. When an appropriate viscosity was shown after cooled, the remaining watery ingredients

including kojic acid were added slowly thereto and stirred to be homogenized. After leaving the resulting product for maturity, an end product was obtained.

Preparation Example 5: Preparation of Cream [Table 4]

With the above ingredients, a cream comprising mandelic acid was prepared according to an ordinary method for preparing creams .

Although the present invention has been described with reference to certain exemplary embodiments thereof, it will be understood by those skilled in the art that a variety of modifications may be made therein without departing from the spirit or scope of the present invention defined by the appended claims and their equivalents .

[industrial Applicability] The mandelic acid in accordance with the present invention shows a selective inhibitory effect that inhibits the growth of pathogenic bacteria, not affecting the growth of normal bacteria in the vaginal canal, and decreases the viability .rate of the pathogenic bacteria in exponential and stationary phases, thus being effectively used as an agent for treatment of chronic vaginitis.