KR20070017451A - Composition for precaution treatment having synergism for antimicrobial infection and antiinflammatory action and treatment for athletes foot provided by using them - Google Patents

Abstract

 The present invention relates to a composition useful for the prevention and treatment of antimicrobial infection and anti-inflammatory action, and to the athlete's foot therapeutic agent obtained by using the same, comprising suctin, citral, carbacroll and thymol as an active ingredient.

The pharmaceutical composition provided by the present invention is effective in antifungal action, skin protection, moisturizing effect, and the like, by directly acting on and killing fungi causing athlete's foot by containing suctintin, citral, carbacroll and thymol as active ingredients. Inflammatory effect is also excellent, and as an adjuvant therapy of continuous athlete's foot therapy, it shows synergistic effect to increase secondary healing and prevention effect.

Furthermore, in addition to treating athlete's foot, it is possible to provide complementary natural complex antimicrobial agents having immunostimulating action, bronchodilating action and anti-inflammatory action.

Suspectin, citral, carbacrol, thymol, antibacterial infection, anti-inflammatory, athlete's foot      

Description

COMPOSITION FOR PRECAUTION TREATMENT HAVING SYNERGISM FOR ANTIMICROBIAL INFECTION AND ANTIINFLAMMATORY ACTION AND TREATMENT FOR ATHLETES FOOT PROVIDED BY USING THEM

1 is a block diagram for explaining the extraction process of the suspectin for use in the present invention,

Figure 2 is a photograph of skin stimulation test 24 hours after supeptin administration,

Figure 3 is a photograph of eye irritation test for the wash group of suspectin,

Figure 4 is an eye irritation test photograph of the non-washing group of the suspectin

Figure 5 is a graph showing the inhibitory effect of NO generation of the suspectin after endotoxin treatment,

Figure 6 is a mRNA expression showing the anti-inflammatory action of the serpentine as a dose-dependent inhibitory response,

Figure 7 is a photograph showing the antifungal action of the formulation formulated in the present invention.

The present invention is useful compositions and to reach on the athlete's foot treatment obtained by using, more particularly, anti-bacterial infections and anti-inflammatory action as well as root pathogens of tricot piton of athlete's foot Brun (Trichophyton the prevention and treatment for anti-bacterial infections and anti-inflammatory action rubrun ), Trichophyton mentagrophytes , Epidermophyton floccusum , and related to athlete's foot treatment.

At present, the athlete's foot is used for the treatment of athlete's foot for oral use such as oral triconazole and ketoconazole, and as an ointment, there are various formulations such as ropelocks (Hanpok medicine). Athlete's foot treatment requires long-term treatment of at least two months to one year and is difficult to cure with a single dose. As a side effect of such long-term treatment, there are many side effects such as hepatotoxicity, so it is required to develop a new auxiliary athlete's foot treatment without side effects.

In addition, the athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot athlete's foot medicine is Korea Patent Publication No. 2003-0045711, pack using paraffin wax is Patent Publication No. 2002-0048535 Athlete's foot treatment is disclosed in Korean Patent Publication No. 194-0005317, and as an active ingredient, an athlete's foot therapeutic agent is disclosed as Patent Publication No. 1991-0002464, but all of the active ingredients Not only do not have enough data on the antifungal action, but only one action has a feature that does not have a satisfactory effect. Therefore, effective athlete's foot treatment should be exposed to sufficient drug solution (concentration) for a sufficient time. Staphylococcus aureus , which acts as an antibiotic resistance strain and is a problem for bacterial infection, is infected with skin and combined infection with athlete's foot. There is a problem that can not be treated with the antibacterial agent currently in use.

On the other hand, respiratory and inflammatory got the like acting killing action and mujomgyun strong antifungal citral, carbazole scroll and thymol are known in the action is known to have an excellent effect on Staphylococcus aureus (Staphylococcus aureus) is a kind of essential oil . Among them, citral is a lemon-like fragrance contained in everyday plants such as grapefruit and is harmless to the human body licensed as Kyungin Food and Drug Administration Food Additive No. 101.

In addition, carbacrol and thymol are components obtained from various plants, and mainly act on bacterial cell walls to denature and coagulate proteins in the cell wall structure, and also act on the cytoplasmic membrane to change the permeability of cations, thereby damaging cell reproduction. Eventually, it is known to be excellent in its role in killing, particularly in the parasitic pathogenic microorganisms within the cell, thereby inhibiting the cells and the pathogenic microorganisms by simultaneously dropping the infected cells themselves (see US Pat. No. 6,322,825).

Accordingly, the present inventors have studied to solve the problems described above, and as a result of the patented strain of suctinine which has not been developed as a conventional athlete's foot treatment for citral, carbacroll and thymol, which has an excellent effect on staphylococcus aureus Completion of the present invention was found to include a complex of lipopeptides produced by Bacillus subtillus complex BC1212 as an active ingredient to prepare a composition excellent in the prevention and treatment of antimicrobial infections and anti-inflammatory effects. Reached.

In addition, in the present invention, as well as effective antifungal action and skin protection, moisturizing effect directly acting on the fungus causing the athlete's foot killing effect, as well as excellent anti-inflammatory effect as a secondary therapy of athlete's foot therapy, secondary healing effect and prevention effect To provide athlete's foot treatment to increase.

Furthermore, the present invention is to provide a therapeutic agent for athlete's foot as well as a liquid type or powder type as well as a foot bath type therapeutic agent that can be applied by various methods in the prevention and treatment.

According to one aspect of the invention,

Provided is a composition for preventing and treating antimicrobial infections and anti-inflammatory actions comprising suspectin, citral, carbacroll and thymol as active ingredients.

According to the second aspect of the present invention,

1-50% by weight of suspectin;

1 to 30% by weight of one or more plant extracts selected from citral, carbacroll and thymol;

0.01 to 3% by weight of one or more accessory ingredients selected from sodium benzoate, allantoin, and sodium propionate; And at least one formulation agent selected from dietary fiber and water soluble collagen as the balance thereof. Athlete's foot treatment is provided comprising a.

According to the third aspect of the present invention,

1-50% by weight of suspectin;

1 to 30% by weight of one or more plant extracts selected from citral, carbacroll and thymol;

1 to 10% by weight of one or more herbal extracts selected from young leaf, Angelica, Cervix, Caesar, poisonous, peony, creation, health, natural, licorice, mint, dew, sessin and sewage rate; 0.01 to 3% by weight of one or more accessory ingredients selected from sodium benzoate, allantoin, and sodium propionate; And water-soluble collagen as the remainder; Athlete's foot treatment is provided comprising a.

Hereinafter, the present invention will be described in more detail.

The present invention is based on surfactins isolated and purified from microorganisms, and it is useful for preventing and treating athlete's foot, which is newly formed by mixing carvacrol, thymol and citral, which are plant extracts. A composition and an athlete's foot therapeutic agent composition are provided.

First, the active ingredient of the composition according to the present invention, the main ingredient (Surfactins) is a natural substance extracted from the microorganism ( Bacillus spp. ) Is a kind of low-molecular lipopeptides, antiviral, antimicrobial, anti-microplasma, anti-fungal It is known to have antithrombotic action. As shown in the block diagram of FIG. 1, the extraction method can be obtained by culturing the strain, centrifugation, and then extracting the supernatant with ethyl acetate. have.

Citral, an active ingredient of the composition according to the present invention, is a natural substance extracted from grapefruit and various plants, has a molecular weight of 152.24, and is a colorless or pale yellow liquid with a lemon-like scent and thus as a perfume or mouthwash. It is a safe substance used as a cleaning agent, has excellent effects on gram-negative and gram-positive bacteria, and exhibits antifungal action, and is soluble in alcohol.

In addition, carbachol and thymol, the active ingredients of the composition according to the present invention, respectively, promote tissue regeneration and also have an immune enhancing function, thereby helping to cure and prevent disease (see Boskaboddy et al, 2003).

Therefore, such a combination of suctinine, citral, carbacroll and thymol is complementary to each other to become a novel functional new natural antimicrobial agent with immunostimulatory, bronchial dilatation and anti-inflammatory effects in addition to athlete's foot treatment. It is preferable to mix pectin, citral, carbacroll and thymol in the weight ratio of 1-10: 0.1-5: 0.1-5: 0.01-5, respectively.

At this time, if the suspectin is less than 1 weight ratio, as in Example 2 (composite 2) described later, the effect on the athlete's foot is insufficient, and if both citral, carbacrol and thymol are less than 0.1 weight ratio for anti-inflammatory and antibacterial action If the effect is low, and citral, carbacroll and thymol exceed 5 weight ratio, the effect on anti-inflammatory action and athlete's foot treatment is increased, but there is a disadvantage that stress and foot stimulation may be caused by odor. In addition, when the excess amount of suptin is added in excess of 10 weight ratio, there is a disadvantage in that the production cost increases and skin irritation increases the unit price and poisoning of the product.

In addition, such suspectin, citral, carbacroll and thymol can be prepared as a combined athlete's foot athlete, in which case the supetin is 1 to 50% by weight based on the total weight of the therapeutic agent, and citral, carbacro And at least one plant extract selected from thymol can sufficiently exert its synergistic effect when added in an amount of 1 to 30% by weight, based on the total weight of the therapeutic agent. In other words, it can be used as a treatment for infectious diseases and disinfectants of resistant strains caused by the use of existing oral antifungal and chemotherapeutic agents. In addition, the present invention will provide athlete's foot athletes' agents useful for the prevention, treatment and alleviation of inflammation of athlete's foot, which are effective against acute and chronic athlete's foot infections.

On the other hand, as an auxiliary component for the composition and athlete's foot treatment agent may be added sodium benzoate, allantoin (allantoin: 5 ~ uraidhydantoin) and sodium propionate (Sodium Propionate).

Sodium benzoate (Sodium benzonate) is a drug that is used as a preservative because of the preservative effect to increase the antibacterial action of the composition. The preferred content of sodium benzoate is 0.01 to 1.0% by weight based on the total weight of the composition or the therapeutic agent, there is a problem that the effect is reduced or the manufacturing cost rises outside the above range.

In addition, allantoin (allantoin: 5 to uraidhydantoin) is a substance produced by the decomposition of uric acid by uricase, and it synergizes with citral due to the wound healing promoting action that revives the cells of wound tissues to repair inflammation. To further promote. Preferred content of allantoin is 0.1 to 1.0% by weight based on the total weight of the composition or therapeutic agent, there is a problem that the effect is reduced or the allantoin toxicity is increased outside the above range.

In addition, sodium propionate (Sodium Propionate) is an antifungal substance that acts to inhibit the fungi that cause mastitis. Its preferred content is 0.1 to 1.0% by weight based on the total weight of the composition or therapeutic agent, there is a problem in that the effect is reduced or the toxicity due to propionic acid increases outside the above range.

In addition to the above components, herbal extracts may be used, and specific components include, but are not limited to, leaflets, donkeys, cheonggung, gages, venom, peony, creation, health, cheoncho, licorice, peppermint, dew, sessin, sesame oil It is preferable to add, and it is more preferable to mix and use 1 or more types among them. The content is a range that can improve skin protection, skin moisturizing action, skin disease, blood circulation of the foot is preferably added to about 1 to 10% by weight based on the total weight of the composition or therapeutic agent.

In addition, an anti-inflammatory steroidal anti-inflammatory agent may be added, and preferably 0.005 to 0.5% by weight of dexamethasone phosphate based on the total weight of the composition or therapeutic agent. At this time, if the range is out of effect or there is a problem remaining in the body.

In addition, an appropriate amount of antihistamine may be added for vasoconstriction, secretion suppression and sedation of the inflammation site. As the antihistamines used in the composition, any type of antihistamine can be used as long as it is effective and safe for humans and animals.However, 0.01 to 0.1% by weight of tripelenamine hydrochloride based on the total weight of the composition or therapeutic agent. Preference is given to using. In addition, there is a problem that remains in the body when used in inorganic matters outside the above range.

In addition, various bases can be used as the base, including oily ointment. The oily ointment is not limited thereto, but petroleum jelly, vegetable oil, and the like may be used, and a water-soluble base may also be used depending on the purpose of use.

The composition or athlete's foot therapeutic agent prepared by the present invention can be used in various formulations, and may be formulated using diluents or excipients such as extenders, binders, wetting agents, disintegrants, surfactants, and the like, which are commonly used.

Solid preparations for foot baths include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, or the like in lignan and lactone compounds and derivatives thereof. It is prepared by mixing lactose, gelatin and collagen. In addition, lubricants such as magnesium stearate, talc may also be used in addition to simple excipients.

Liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. In addition, preparations for foot baths include sterile aqueous solutions, water-insoluble solvents, suspensions, emulsions, and lyophilizers, wherein the water-insoluble solvents and suspensions include vegetable oils such as propylene glycol, polyethylene glycol, and olive oil, and ethyl oleate. Injectable esters, such as these, etc. are mentioned.

The content in the above-mentioned preparation of the composition or athlete's foot therapeutic agent according to the present invention may be appropriately selected according to the absorbency, inactivation rate, excretion rate, age and condition of the active ingredient in the body. The dosage of the composition or athlete's foot therapeutic agent is 1 to 10 g / L, preferably 1 to 5 g / L, and can be used by foot bath or spraying 3 to 10 times a day for 30 minutes once a day.

EMBODIMENT OF THE INVENTION Hereinafter, the form for implementing this invention is demonstrated in detail, taking an example. However, the following examples are only for illustrating the present invention, and the present invention is not limited thereto.

Example 1 Skin Stimulation Test of Suspectin

In this example, the safety test for the skin irritation against the serpentine was carried out based on the toxicity test criteria such as drugs.

As a test animal, a 7-week-old New Zealand white rabbit, which was purchased from Hyochang Corporation after 7 days of purification and confirmed that there was no skin infection by bacteria and fungi, was applied 24 hours before the animal's back clipper. After depilation, one rabbit was treated with four sections, each of which was divided into treatment, control, non-brasion, and abrasion sites, and then tested. Here, by using the tip of the syringe needle to the scratched area was damaged to the extent that the epidermis does not bleed the epidermis to create a scratched state.

In order to treat the test substance and the control material, a surgical tape 5cm × 5cm is made, and a 25m × 25cm rectangle is cut out here, and the window frame shape is bonded to the skin, and 3 layers of gauze (2.5cm × 2.5) is applied to the skin. cm size).

Concentrated 10-fold concentrate (50 mg / ml) (hereinafter referred to as 'Test Substance-1') of the highest dose used for the suspectin was used as the test substance and tap water. Test substance-1 or 1 ml of tap water was added dropwise to the gauze at the designated place in the four compartments. Feed consumption, drinking water and clinical symptoms were observed daily for one week after the administration of the test substance, including the period of purification, and death was also confirmed.

As a result, no changes in general symptoms due to the test substance were observed in all four rabbits administered Test substance-1, and no animals were killed during the test period. On the other hand, body weight and temperature changes were measured before administration of test substance and 7 days after administration, respectively. As a result, no change was observed before and after administration.

Determination of the site of application of the test substance was determined by removing the test substance ~ 1 well with lukewarm water 24 hours after the administration of Test substance-1, and then observing the skin irritation reactions such as erythema, skin formation, and edema formation at the administration site. .

The skin reaction was evaluated in accordance with the Toxicity Test Criteria of the National Health and Safety Research Institute No. 94-3 (National Safety Research Institute, 1994). Of these, the determination of irritation was 24 hours according to the suggestion of Draize. And primary stimulation index (PII) was obtained using the results of only 72 hours. (Draize, 1959; Obra et al., 1992). Here, the degree of irritation of the substance was evaluated according to the criteria shown in Table 1 below (irritation grade for the first skin irritation reaction), and applied to the skin of rabbits 24 hours and 72 hours after application of 10-fold concentrated serpentine. The effect on skin formation was observed and the results are shown in Table 2 and FIG. 2.

Rating Range of Primary Stimulus Index Mild irritant <2 Moderate irritant 2 to 5 Severe irritant > 5

part Control site Test site change Erythema and crust edema Erythema and crust edema With the mirror Abrasion With the mirror Abrasion With the mirror Abrasion With the mirror Abrasion Observation time 24h 72h 24h 72h 24h 72h 24h 72h 24h 72h 24h 72h 24h 72h 24h 72h Rabbit 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rabbit 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rabbit 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rabbit 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Average 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Average sum 0 0 0 0 Total score 0 0 * P.I.I. 0 0

Primary irritation index = total score / 4

As shown in the table above, irritation was not found in both the non-abrasive and abrasion areas 24 hours after the application of the test substance, and the effect on the edema could not be observed. In addition, no erythema to skin or edema was observed in both the abrasion and non-brain areas of the entire test group administered with the control.

However, during the test period, it was confirmed that the wound area of the abrasion site to which the test substance was administered showed faster wound healing than the abrasion site to which the control material was administered. From these results, it is speculated that the serpentin has a wound healing component, and it is also thought to exhibit a relieving effect on skin inflammation. Furthermore, from the point where the skin primary (local) irritation index (P.I.I.) is 0, it was evaluated as a non-irritant substance at the test dose.

Example 2 Eye Stimulation Test of Suspectin

In this example, safety test for eye irritation was performed on Test Substance-1 based on the toxicity test standard of medicines (No. 94-3 of the National Institute of Health and Safety (1994)).

As experimental animals, rabbits, 7-year-old New Zealand white species, were purchased from Hyochang Corporation and after 7 days of purification, they were confirmed that there was no eye infection by bacteria and fungi. The same serpentine concentrate (Test Substance-1) as used in Example 1 was instilled in the eye using a syringe.

The daily consumption of feed, drinking water, and clinical symptoms were observed daily for one week after the administration of the test substance, including the period of acclimatization.

On the other hand, in the determination of the application site of the test substance, the test substance-1 was well removed with lukewarm water 24 hours after the administration of the test substance-1, and the eye irritation reactions of the cornea, the iris, and the conjunctiva were observed. The evaluation of the eye irritation response was evaluated according to the toxicology test standards of the National Health and Safety Research Institute No. 94-3 (National Safety Research Institute, 1994). Among them, the primary irritation index (MOI) was obtained. , The results are shown in Table 3 and FIGS. 3 and 4.

No. group Time after application 3 hours 1 day 2 days 3 days 4 days 7 days A.O.I. Rabbit 1 cornea 0 0 0 0 0 0 0 Iris 0 0 0 0 0 0 0 conjunctiva 0 0 0 0 0 0 0 Rabbit 2 cornea 0 0 0 0 0 0 0 Iris 0 0 0 0 0 0 0 conjunctiva 0 0 0 0 0 0 0 Rabbit 3 cornea 0 0 0 0 0 0 0 Iris 0 0 0 0 0 0 0 conjunctiva 0 0 0 0 0 0 0 Rabbit 4 cornea 0 0 0 0 0 0 0 Iris 0 0 0 0 0 0 0 conjunctiva 0 0 0 0 0 0 0 M.O.I. 0 0 00 0 0 0 0 I.O.I (day 7) 3 hours 1 day 2 days 3 days 4 days 7 days A.O.I.

* A.O.I: Acute ocular irritation index

* M.O.I .: Mean ocular irritation index

I.O.I .: Individual ocular irritation index

 As shown in the table above, no abnormal signs were found in the cornea, iris and conjunctiva. From this, it could be confirmed that the 10-fold concentrated suctin had no effect on the eyes.

Example 3: Anti-inflammatory Response of Suspectin

In this example, the effect of anti-inflammatory prevention on suspectin was investigated at the cellular level.

RAW 264.7 cells were treated for 24 hours with multiple concentrations of suptin in the presence of 1 μg / ml LPS. Dose-dependent effects of serpentin on cytokine mRNA expression were treated dose-dependently and the results are summarized in Tables 4 and 5,6.

TABLE 4

(unit: %)

As a result, LPS induced the inflammatory response by strongly expressing COX2, but COX2 was suppressed by LPS when treated with suctin.

The expression of IL-2 was also inhibited by the average of 30% of the expression level of LPS by suspectin, and the expression of iNOS by LPS was also reduced to the control level by 15%. Inflammatory mediators, TNF-α, were also inhibited by controltin to control levels.

Taken together, these results show that suspectin shows the results of suppressing TNF-α and iNOS by endotoxin, which is an inflammatory mediator expressed by endotoxin, and concentration-dependently inhibiting NO generation by iNOS. It became.

Example 4 Antibacterial Activity Test

In this example, the effect was verified by the diffusion method in order to confirm the antimicrobial activity of the combination therapy consisting of suspectin, citral, carbacroll and thymol.

Five kinds of Staphylococcus aureus KCCM40510, KCCM11593, KCCM41294, KCCM40881, and KCCM41291, which are Gram-positive strains, were distributed by the Korea Microorganism Conservation Center (KCTC) to Muller-Hinton, an antimicrobial susceptibility test medium. Inoculation was precultured at 37 ° C.

The precultured strains were inoculated in Müllerton medium and the test medium was prepared. The effect of the first antimicrobial activity on the ingredients shown in Table 1 was verified by the diffusion method using a paper disk. In other words, 60 μl of the components shown in Table 1 were adsorbed on a paper disk, and then placed on a test medium, incubated at 37 ° C. overnight, incubated for 18 hours, and then the ring was measured in mm and the results are shown in Table 4 together.

division KCCM40510 KCCM11593 KCCM41294 KCCM40881 KCCM41291 Skin irritation Example 2% complex 1 18 17 16 17 14 - 2% complex 2 18 15 18 16 11 - 2% complex 3 18 16 18 18 15 + Comparative example 2% citral 18 17 14 17 12 - 2% Kabakrole 10 10 11 11 9 - 2% thymol 8 9 9 8 8 - 2% Suspectin 11 10 11 10 10 - Control Vegetable oil 8 8 8 8 8 - * Compound 1-Sfectin: Citral: Carbachol: Timol (1: 1: 0.1: 0.01) * Compound 2-Suptintin: Citral: Carbaccro: Timol (0.01: 0.1: 1: 1) * Compound 3- Servectin: Citral: Carbachol: Timol (10: 5: 5: 5)

As shown in Table 5, as a comparative example, the composite 2 showed better antimicrobial activity in the examples than the suspectin, citral, carbacroll, and thymol alone, and the antimicrobial activity was better in the composition of the composite 1 than the composite 2 The effect was shown.

On the other hand, it was confirmed from the result that the combination agent 2 had superior antimicrobial activity than the single agent, and it was confirmed that there was no antagonism between suctinin, citral, carbacroll and thymol, and from the result that the combination agent 2 had better antibacterial activity than the combination agent 2 Judging from the above, it was confirmed that the antimicrobial activity was excellent only when a certain amount of suctin was included. In addition, the antimicrobial activity in the composite agent 3 having a compounding weight ratio or more was not different from that shown in the composite agent 2. Therefore, the combination of more than 10 weight ratio of suspectin has the toxic effect of skin irritation and the production cost is high, so that it is not available as a product and when any component of citral, carbacrol and thymol exceeds 5 by weight Stimulation and skin irritation due to odor is so severe, it should be made in the formulation ratio applied above.

Example 5 Antifungal Force Experiment

In this example, in order to observe the antifungal power of the complex athlete's foot fungal therapeutic agent consisting of suspectin, citral, carbacroll and thymol, the effect was verified using a disk diffusion method and the results are summarized in Table 6 and FIG. 7.

The medium prepared for cultivation of athlete's foot and dandruff using sterilized Petri dishes includes Saboraud dextrose agar, 40 g of dextrose, 10 g of peptone, and 15 g of starch. SDA) medium was used.

100 μl of each strain was smeared on the medium, and 60 μl of the test substance was absorbed into a sterilized paper disc (8 mm) at the center of the medium, and the antifungal activity was observed. At this time, the strain used in the test was athlete's foot Trichophyton rubrun, Trichophyton mentagrophytes , Epidermophyton floccusum, were used as dandruff, and Pityrosporum ovale , and vulvitis Or Candida albicans was used as a perianal candidiasis strain.

division T. pyrun (T. rubrun) Trichophyton Mentagrophytes (T.mentagro ~ phytes) Epidermo Phyton Flucuzum (E.floccusum) Candida albicans (C.albicans) Pytilosporum Obale (P.ovale) Skin irritation Example 2% compound 1 18 16 16 16 14 - 2% complex 2 14 12 14 14 11 - 2% complex 3 18 16 18 17 15 + Comparative example 2% citral 15 12 11 12 12 - 2% Kabakrole 10 10 11 11 9 - 2% thymol 8 9 9 8 8 - 2% Suspectin 11 10 11 10 10 - Control Tween 20 To To To To To - * Compound 1-Sfectin: Citral: Carbachol: Timol (1: 1: 0.1: 0.01) * Compound 2-Suptintin: Citral: Carbaccro: Timol (0.01: 0.1: 1: 1) * Compound 3- Servectin: Citral: Carbachol: Timol (10: 5: 5: 5)

As shown in the above table, Combination 2 consisting of suptin, carbacroll, thymol and citral showed an excellent antimicrobial effect than suspectin, carbacroll, thymol and citral alone, and the antimicrobial activity of complex 1 was much higher than that of complex 2 It was confirmed that it was excellent.

Therefore, the antifungal activity was shown to be different according to the proper mixing ratio of the ingredients, and as shown in the complex 2, the antifungal activity was confirmed to be maximized when composed of the proper ratio. Like the antimicrobial activity, the antifungal activity is lowered in the compounding agent 1 which is less than each compounding ratio like the compounding agent 1 when it is out of the weight ratio in the present invention. Antifungal activity is not greatly improved while skin irritation is increased, resulting in poisoning.

Example 6: Toxicity Test

2,000 mg / Kg, 680 mg / Kg, 230 mg / g of a combination consisting of suptin: citral: carbacroll: thymol = 1: 1: 0.1: 0.01 per unit dose for 5 ICR mice (weight: 25-30 g) Once oral toxicity was administered in units of Kg, 75mg / Kg and visually observed at two-week intervals. In addition, mortality, general symptoms and changes in body weight were observed for two weeks after the end of the administration, and autopsies were also checked for abnormalities.

As a result, it was confirmed that the LD ₅₀ by the combination administration was safe as more than 2,000mg / kg, no specific symptoms at all doses, and the autopsy showed no difference from the control group.

Example 7 Antifungal Force Experiment

In this example, the effect was verified by using the disk diffusion method in the same manner as in Example 2 to observe the antifungal force for the complex athlete's foot therapeutic agent consisting of suspectin, citral, carbacroll, thymol and auxiliary components. By adding three accessory ingredients described in Table 7 below, activity against athlete's foot was measured in four strains.

division T. pyrun (T. rubrun) Trichophyton Mentagrophytes Epidermo Phyton Flucuzum (E.floccusum) Candida albicans  Example Compound 1 10-fold dilution 10-fold dilution 10-fold dilution 100-fold dilution Compound 2 10-fold dilution 10-fold dilution 10-fold dilution 10-fold dilution Compound 3 100-fold dilution 100-fold dilution 100-fold dilution 100-fold dilution Compound 4 100-fold dilution 1,000-fold dilution 100-fold dilution 100-fold dilution Control Tween 20 Growth Growth Growth Growth * Compound 1-Sectin: Citral: Carbacrol: Timol = 1: 1: 0.1: 0.01 weight ratio (2g / 100ml (Tween 20)) * Compound 2-Compound 1 + Sodium Benzoate (0.02g) + Allantoin (0.2g ) / 100ml (Tween 20) * Compound 3-Compound 1 + Sodium Benzoate (0.02g) + Sodium Propionate (0.2g) / 100ml (Tween 20) * Compound 4-Compound 1 + Sodium Benzoate (0.02g) + Sodium Propionate ( 0.2 g) + Allantoin (0.2 g) / 100 ml (Tween 20)

As shown in the table, it was confirmed that the use of sodium benzoate as an auxiliary component showed the most excellent antifungal activity in the combination 3 and 4, the antibacterial activity by the auxiliary component did not decrease in all the combinations tested.

Preparation Example 1: Preparation of athlete's foot

1 ml of a combination of Suspectin: Citral: Cavacrorol: Thymol = 1: 1: 0.1: 0.01 was mixed with Tween 20 or dietary fiber into a total 10 ml volume pack and then dissolved in 1 L of water.

More specific components are as follows.

   1 ml of compound

   Dietary Fiber 10 ml

   Sodium benzoate 0.01-0.1 g

   Allantoin 0.1 to 1 g

   Sodium propionate ... 0.1-0.3 g

Preparation Example 2 Preparation of Athlete's Foot Powder

The composite agent having the composition described in Preparation Example 1 was adsorbed to water-soluble collagen to make a total 10 g of a powdered formulation, and then dissolved in 1 L of water.

More specific components are as follows.

   1 to 5 g of a compound

   Sodium benzoate 0.01-0.1 g

   Allantoin ··············· 0.1 to 1 g

   Sodium propionate 0.1 to 0.3 g

   Tripyleneamine hydrochloric acid 0.1 to 0.3 g

   Salt ·········· 3 g

   Excipient (collagen)

Preparation Example 3: Preparation of foot bath treatment for treating athlete's foot

3g of the herbal extract powder extracted after drying in the composite having the composition described in Preparation Example 1 was dissolved in water-soluble collagen, and then made into powder or liquid formulation in a total volume of 10 ml using ethyl alcohol, distilled water and liquid paraffin. It was then dissolved in 1 L of water. Herbal extracts were used to select one or more of the leaves, Angelica, cheonggung, gyeji, poisonous, peony, creation, health, cheoncho, licorice, mint, dew, sessin, sewage.

The composition ratio of the herbal foot athletes foot therapeutics is as follows.

   Complex agent ···················· 1 to 5 g

   Herbal Extracts ··················

   Water Soluble Collagen 1 ~ 5 g

   Ethyl Alcohol, Distilled Water and Liquid Paraffin ·······

Foot bath treatment for the treatment of athlete's foot is prepared by adding herbal extracts can help skin protection, skin moisturizing, skin disease, athlete's foot prevention and treatment as well as blood circulation of the foot.

As commercial preparations 1,2,3 and Comparative Examples, commercially available rofurox was applied to 20 athlete's foot athletes, respectively, and the results are summarized in Tables 8 to 10 below.

20 athlete's foot athletes who applied Rofurox 2 months 20 athlete's foot athletes who applied Preparation Example 1 for 30 minutes a day for 15 days Antimicrobial action o o Skin protection o o Moisturizing effect - o Anti-inflammatory effect - o Exfoliation effect - o

20 athlete's foot athletes who applied Rofurox 2 months 20 athlete's foot athletes who applied Preparation Example 2 Antimicrobial action o o Skin protection o o Moisturizing effect - o Anti-inflammatory effect - o Exfoliation effect - o

20 athlete's foot athletes who applied Rofurox 2 months 20 athlete's foot athletes who applied Preparation Example 3 Antimicrobial action o o Skin protection o o Moisturizing effect - o Anti-inflammatory effect - o Exfoliation effect - o

In the case of Lofurox, while the gel type is applied, the product of the present invention shows an excellent effect when the foot bath in hot water or cold water for 30 minutes a day in the form of a foot bath. In particular, as can be seen from the above results, it is clear that the athlete's foot therapeutic agent prepared by the present invention is excellent in moisturizing and anti-inflammatory effects than the conventionally marketed products and can be much more athlete's foot therapeutic effect in a short time.

As described above, the pharmaceutical composition provided by the present invention contains suspectin, citral, carbacroll and thymol as active ingredients, thereby directly acting on and killing fungi causing athlete's foot, and protecting against skin and moisturizing. As well as effective on the back, and also has an excellent anti-inflammatory effect, it has a synergistic effect of increasing secondary healing and prevention effects as a continuous therapy for athlete's foot.

Furthermore, in addition to treating athlete's foot, it is possible to provide a complementary natural complex antimicrobial agent having immunostimulating action, bronchodilating action and anti-inflammatory action.

Claims (6)

Prophylactic, anti-inflammatory and anti-inflammatory composition comprising suctin, citral, carbachol and thymol as active ingredients [Claim 2] The antimicrobial infection and anti-inflammatory action of claim 1, wherein the suspectin, citral, carbacroll and thymol are each included in a weight ratio of 1 to 10: 0.1 to 5: 0.1 to 5: 0.01 to 5, respectively. Prevention and Treatment Composition The method according to claim 2, further comprising one or more herbal extracts selected from love leaf, Angelica, cheonggung, gyeji, poisonous, peony, creation, health, cheoncho, licorice, mint, dew, sessin and effluent. Prevention and treatment composition for antimicrobial infection and anti-inflammatory action The prevention of antimicrobial infection and anti-inflammatory action according to any one of claims 1 to 3, further comprising one or more accessory ingredients selected from sodium benzoate, allantoin, sodium propionate, dietary fiber and water soluble collagen. ㆍ Therapeutic composition 1-50% by weight of suspectin; 1 to 30% by weight of one or more plant extracts selected from citral, carbacroll and thymol; 0.01 to 3% by weight of one or more accessory ingredients selected from sodium benzoate, allantoin, and sodium propionate; And at least one formulation agent selected from dietary fiber and water soluble collagen as the balance thereof. Athlete's foot treatment agent comprising a 1-50% by weight of suspectin; 1 to 30% by weight of one or more plant extracts selected from citral, carbacroll and thymol; 1-10% by weight of three or more herbal extracts selected from young leaf, Angelica, celestial arch, lanceolate, venom, peony, creation, health, vinegar, licorice, mint, dew, sessin and sewage rate; 0.01 to 3% by weight of one or more accessory ingredients selected from sodium benzoate, allantoin, and sodium propionate; And As the remainder, water-soluble collagen; Athlete's foot treatment agent comprising a

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