WO2014104577A1

WO2014104577A1 - Composition including castor oil extracted from castor beans using hexane, undecylenic acid, propyl alcohol, propylene glycol, and water for external use on skin for preventing or treating athlete's foot

Info

Publication number: WO2014104577A1
Application number: PCT/KR2013/010516
Authority: WO
Inventors: 전상문
Original assignee: Jean Sang Moon
Priority date: 2012-12-31
Filing date: 2013-11-19
Publication date: 2014-07-03
Also published as: KR101281470B1

Abstract

The composition of the present invention relates to a composition including castor oil extracted from castor beans by using hexane, undecylenic acid, propyl alcohol, propylene glycol, and water for external use on the skin for preventing or treating athlete's foot. Among the constituent components of the composition, the castor oil extracted from castor beans using hexane exhibits better antifungal activity compared to that of castor oil extracted using a compression method at a high temperature under high pressure. Thus, through the excellent antifungal effect of the composition, various kinds of athlete's foot such as athlete's foot erupting on the hands and feet, tinea cruris around the inguinal, tinea unguium (athlete's foot on nails) erupting on the fingernails or toenails, tinea capitis erupting on the head, tinea corporis erupting on the body may be easily treated.

Description

Athlete's foot skin composition containing castor oil, undecylenic acid, propyl alcohol, propylene glycol and water extracted from castor hexane

The present invention relates to a skin external preparation composition for athlete's foot prevention or treatment containing castor oil extracted from hexane, undecylenic acid, propyl alcohol, propylene glycol and water.

Athlete's foot (tinea pedis) is one of the most common symptoms of fungal infections. It is a parasitic and multiplying skin disease in which the fungus dissolves the keratin of the skin and nourish it. Among the fungi having affinity for the skin, trichophyton rubrum , Trichophyton mentagrophytes , Microsporum canis , Candida albicans , etc. They penetrate the keratin of the skin and cause symptoms such as itching, redness, and inflammation. The exacerbation of these fungal infections is known to depend on the environment at the site of infection and the individual's ability to immunize. On the other hand, the modern society mainly wears shoes or socks for a long time. After the infection of the fungus, if the skin is kept closed for a long time by the shoes and socks, the fungus proliferates due to heat and moisture of the infected area. This improves, and athlete's foot occurs.

Athlete's foot is found in most parts of the body in funky, keratin-rich, moist, warm areas (toes, soles, toenails, nails, flanks, groin, and flesh). In general, it is easy to think that only foot is the athlete's foot, but it includes not only feet and hands, but also ridges around the groin, nails or nails on the toe, nail whites on the head, and body whites on the body. do. According to statistics, more than 10% of the total population suffers from athlete's foot, most frequently in their 20s and 40s. Rarely occurs in children.

Athlete's foot is divided into a basal, hydrophobic, and keratinous form depending on the developmental form. The interstitial type occurs mainly between the toes, because the area is not easily communicated with the outside air and the moisture is high, so the fungus is easily inhabited. When the intercostal athlete's foot occurs, itching is severe, the skin is whitened and cracked, causing an unpleasant odor, and sometimes spreads to both toes and soles. In the athlete's foot type, blisters of various sizes are produced, and when it is scratched due to itching, the skin is peeled off frequently, and a lot of sweat is known to deteriorate a lot during the summer sweating. Athlete's foot-type athlete's foot is thickened over the entire sole of the foot and thick, which means that the powder falls. It is easy to develop into chronic refractory athlete's foot.

On the other hand, if left untreated, fungi can penetrate into other parts of the body, such as insteps or toenails, and develop into nail footing. 5% of the entire population of Korea and 20-30% of all athlete's foot athletes It is known to suffer. Nail athlete's foot is a symptom of fungal infection of the toenails or nails, which causes thick keratinization and color change in the nails, and the nails crumble when they progress. In particular, the recent increase in the elderly population and the use of swimming pools or gym spas Increasingly, the likelihood of exposure to athlete's foot fungi increases.

In addition, one of the most common baekbueum occurs in the groin completeness, mainly due to high temperature and high humidity skin conditions, obesity, close clothing and friction between the skin and the skin caused by the athlete's foot fungus is inhabited and accompanied by foot athlete's foot There are many cases. Athlete's foot athlete's foot fungus is usually buried in the inner part of the body, most often occur in men, scrotum, buttocks, thighs are also spread. The condition worsens mainly in wet summers, leaving only black pigmentation in dry winters, and most of the main symptoms disappear. It occurs almost in both groin. The onset begins at the point where the testis touches and then spreads to both groin, and red keratin may begin in the testicle or penis bone without groin invasion. The reason why groin completeness is significantly better in men than in women is because men wear more sealed clothing than women, testicles are more sealed in the groin, and men have a higher frequency of foot athlete's foot.

Athlete's foot is also associated with bad breath. Medically, foot odor is a form of bromidrosis that occurs on the soles of the feet. The soles of the feet have a lot of eccrine gland, which is more sweaty than other skin tissues. As the keratin tissue of the warp is distorted, bacteria and fungi inhabit, causing foot odor. Drunkenness most often occurs on the soles of the feet, but sometimes occurs in other parts of the body, such as the interrogator, or the fold of flesh. Foot odor is most common in young men and middle-aged adults, but there are no statistically significant race differences or gender differences. Foot odor occurs regardless of the season, because the sweat on the sole is caused by emotional tension, not due to a rise in body temperature. In addition, the anxiety of foot odor may make patients more nervous, causing stress symptoms that worsen foot odor and lead to social activity.

On the other hand, athlete's foot tends to recur if not properly rooted, so it often becomes 'companion disease' that must live together for a lifetime. Athlete's foot is suddenly itchy at the beginning of the rainy season. Athlete's most probable environment is the temperature of 37 ℃, moderate humidity, nutrients, etc., summer has all of these conditions, so the athlete's fungus multiplies and rises in summer. However, athlete's foot sticks to the skin even in winter, but the activity is weakened, but the bacteria that boasted strong breeding ability in the humid and warm environment cannot hide well in the winter and hide in the skin.

Harrison, P. V. (Clin. Exp. Dermatol. 17, 467, 1992) shows that athlete's foot is more common in adults than children, and 10 to 15 percent of the adult population in developed countries have athlete's foot or have been infected. Speaking of athlete's foot, it used to be a disease for middle-aged men in the past, but recently, it tends to increase in women, especially young women such as high school girls. This is because both young and old have a lot of social activities, and the time to live outside has increased and the environment for athletes to thrive.

In order to treat athlete's foot, a method of killing athlete's foot causing bacteria or inhibiting the growth of bacteria is considered. The most commonly used therapeutics include antifungal agents, which are used because they are easy to use and have fewer side effects. However, it is difficult to cure only by using a coating agent, and it is common to apply at least several weeks. Next, there is an antifungal drug to eat, the effect of the treatments are good compared to the drug, but side effects such as hepatotoxicity, nephrotoxicity, etc. rarely occurs, so care should be taken in the administration. In the treatment of athlete's foot, it is also used as a steroid preparation to eliminate the dead skin or improve the symptoms by using the keratin softener together, and external preparations, ointments, sprays, etc. prescribed with antifungal and salicylic acid have already been developed. It is also commercialized.

There are two main components of athlete's foot medicine, terbinafine and clotrimazole. Terbinafine has excellent sterilizing effect and has the advantage of being able to see a quick effect in a short time. Clotrimazole, on the other hand, focuses on slow treatment rather than sterilization. Although treatment with clotrimazole takes a long time, it is known to have an advantage over terbinafine products for restoring damaged skin. The drugs are mainly manufactured in cream or ointment type, but they are good for use in the condition that the keratin is severe and becomes hard like a callus. However, in case of athlete's foot athlete's foot, secondary infection caused by skin disease or eczema with athlete's foot, or nail athlete's foot, it is known that it is not good for such drugs. In addition, the components of a wide range of drugs for the treatment of a wide range of skin diseases include corticosteroids that inhibit normal immune responses in addition to the components that kill athlete's foot, which has been controversial.

On the other hand, athlete's foot athletes are usually relapsed even after the appearance of symptoms after treatment, it is difficult to cure if not treated steadily, there is a need for a new type of athlete's foot treatment agent excellent safety and athlete's foot treatment effect without side effects.

Castor oil (castor oil) is a fatty oil obtained by squeezing the seeds of Ricinus communis , also known as castor oil. Castor oil contains ricinoleic acid, palmitic acid, stearic acid, linolenic acid, hydroxystearic acid, trilinolein, and diricinoleine. (diricinolein), monooricinolein (monoricinolein), ricinoleic acid (ricinoleic acid), undecylenic acid (undecylenic acid) is contained, unlike other fatty oils are soluble in alcohol. Castor oil is often taken as a laxative or as a fungicide. It has a burn treatment effect and an excellent antipyretic effect. In addition, it is known to have an excellent effect of suppressing pus due to inflammation in otitis media, and also has a therapeutic effect on pleurisy, peritonitis, ascites, nephritis, keratitis, and the like. In addition, it contains a large amount of unsaturated fatty acid and does not harden at room temperature. Therefore, it is used as lubricating oil, electric insulation, artificial leather, typewriter ink and the like. Castor oil is present in about 45% of the seeds. The seed of the castor is toxic, but not in the oil obtained by pressing, and the toxic remains salty and leftover. Castor oil is pale yellow and slightly viscous and has a peculiar smell like cod liver oil. Unlike most other fatty oils, it is soluble in alcohol. When castor oil is used as a laxative, take 10-20ml per dose. Drinking castor oil rarely causes abdominal pain. Castor oil has a bad smell, taste, and aftertaste, and is difficult to take. Therefore, orange oil and peppermint oil are added 0.5% each and used as flavored castor oil. In addition to pharmaceuticals, it is also used as a raw material for lubricating oil, rod oil, pomade, electrical insulation, artificial leather, typewriter ink, brake oil, carbon paper, oral medicine, and special paints.

Undecylenic acid is an active compound of castor oil and is known to have antibacterial, deodorant and fungicidal action.

On the other hand, the inventors of the present invention while studying the athlete's foot treatment composition containing castor oil and undecylenic acid extracted using hexane is Trichophyton rubrum ( KCTC 6345), Trichophyton mentagrophytes (KCTC) 6077), Microsporum canis (KCTC 6348), Candida albicans ( Candida albicans , KCTC 7965) by confirming the excellent antifungal effect was able to complete the present invention.

In Korean Patent Laid-Open No. 2006-0010742 and US Patent No. 7186416, undecylenic acid may be used as an athlete's foot therapeutic agent, and Korean Patent No. 500577 and US Patent No. 7186416 castor oil may be used as a therapeutic agent for treating athlete's foot athlete's foot. Although it is disclosed that it can be used as a component, it has not been confirmed at all about the external skin composition for athlete's foot treatment containing undecylenic acid and castor oil, or castor oil extracted using hexane.

An object of the present invention is to provide a composition for external athlete's foot for preventing or treating athlete's foot, which contains castor oil, undecylenic acid, propyl alcohol, propylene glycol and water extracted from castor hexane.

The skin external preparation composition for athlete's foot prevention or treatment, castor oil extracted from hexane 0.5 ~ 2% by weight, undecylenic acid 7 ~ 11% by weight, propyl alcohol 30 ~ 50% by weight, propylene glycol 15 ~ 35% by weight and water It may contain 15 to 35% by weight.

The skin external preparation composition for preventing or treating athlete's foot may be a composition having a pH of 6.0 to 6.5 using a triethanolamine solution.

In addition, the athlete's foot is from a fungus selected from the group consisting of Trichophyton rubrum , Trichophyton mentagrophytes , Microsporum canis and Candida albicans It is characterized in that the disease is induced.

The composition is preferably,

(Step 1) Mixing a castor (seeds of Ricinus communis ) ground with normal hexane and stirring at 15 ~ 27 ℃;

(Step 2) collecting the remaining castor oil after removing the solid content from the stirring and separating the remaining hexane by the concentrated vacuum method using a heated bath; And,

(Step 3) 0.5 to 2% by weight of castor oil extracted from the hexane, 7 to 11% by weight undecylene acid, 30 to 50% by weight of propyl alcohol, 15 to 35% by weight of propylene glycol and 15 to 35% by weight of water Mixing and stirring;

It can be prepared through.

In addition, when the mixture is stirred in the third step, it is possible to adjust the pH to 6.0 ~ 6.5 using a triethanolamine solution.

Hereinafter, the present invention will be described in detail.

The castor pulverized product may be extracted with normal hexane to obtain castor oil corresponding to 25 to 45 wt% of the weight of the castor pulverized product.

Normal hexane may be added 2 to 20 times (w / v) of the weight of the castor.

At this time, the mixture of the three steps is mixed evenly in the solution state of the clear and transparent state by adding the triethanolamine solution.

At this time, triethanolamine is used as a neutralizing agent for the mixing of each component of the composition, in addition, it serves as a surfactant, detergent and insect repellent in the composition.

Since the composition of the present invention is used as an external preparation for skin, it is better to avoid the application to a weak spot such as around the eye.

The composition of the present invention can be used as a therapeutic agent for skin fungus, such as athlete's foot, mainly used as a liquid type skin coating, and may be processed and used in sprays, ointments, creams, lotions, patches. In addition, the composition of the present invention can also be used as additives such as cleaning agents, disinfectants.

In addition, the composition of the present invention may further include a physiologically acceptable carrier according to the formulation and the method of use, it may be included in 1.0 to 99.9% by weight of the total external skin composition for athlete's foot prevention or treatment. The dosage of the composition is preferably adjusted according to the severity of athlete's foot symptoms and the health of the patient.

The composition of the present invention relates to a composition for external athlete's foot for preventing or treating athlete's foot containing castor oil, undecylenic acid, propyl alcohol, propylene glycol, and water from which castor is extracted with hexane. The extracted castor oil has better antifungal activity than the castors extracted by high temperature and high pressure compression method. Therefore, through the excellent antifungal effect of the composition, various foot, such as athlete's foot, hand lines around the groin, nail ring or nail claws (nail nail athlete's foot), head ringworm on the head, body ringworm on the body, etc. Athlete's foot can be easily treated.

1 is a photograph showing the results of the antifungal effect of the composition of Example 1-1 of the present invention confirmed using a paper disc diffusion method for Candida albicans .

Figure 2 is a graph showing the results of the antifungal effect of the composition of Example 1-1 of the present invention confirmed using a paper disc diffusion method for Candida albicans .

Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the information provided herein is provided to be thorough and complete, and also to fully convey the spirit of the present invention to those skilled in the art.

<실시예 1. 피마자를 헥산으로 추출한 피마자유, 운데실렌산, 프로필알코올, 프로필렌글리콜 및 물을 함유하는 무좀 예방 또는 치료용 피부 외용제 조성물의 제조><Example 1. Preparation of athlete's foot external preparation composition for athlete's foot prevention or treatment containing castor oil, undecylenic acid, propyl alcohol, propylene glycol and water extracted with hexane>

1 kg of castor (seed of Ricinus communis ) was ground to a size of 100 mesh, mixed with 10 L of normal hexane, and stirred at 25 ° C. room temperature. After that, the seed solids were removed, and the remaining extract was concentrated under reduced pressure using a water bath to separate normal hexane (condensed and recovered as a separated gaseous normal hexane). Collected.

Thereafter, castor oil, undecylenic acid, propyl alcohol, propylene glycol and water extracted using the hexane were mixed and stirred under the conditions shown in Table 1 below, and the pH of the mixed solution was adjusted to 6.0 to 6.5 with a triethanolamine solution. A skin external composition for treating athlete's foot was prepared.

Table 1

Condition	Weight (g)
Condition	Castor oil extracted with hexane	Undecylenic acid	Propyl Alcohol	Propylene glycol	water
Example 1-1	10	90	400	250	250
Example 1-2	5	95	300	300	300
Example 1-3	15	85	500	200	200
Example 1-4	10	70	420	150	350
Example 1-5	10	110	380	350	150

<비교예 1. 비교대상 무좀 예방 또는 치료용 피부 외용제 조성물의 제조><Comparative Example 1. Preparation of skin external preparation composition for preventing or treating athlete's foot>

To prepare a skin external composition for athlete's foot prevention or treatment in the same manner as in Example 1, the components of each composition was prepared with reference to the weight disclosed in Table 2 (Comparative Example 1-1 does not include undecylenic acid no pH adjustment).

TABLE 2

Condition	Weight (g)
Condition	Castor oil extracted with hexane	Crimped Castor Oil	Undecylenic acid	Propyl Alcohol	Propylene glycol	water
Comparative Example 1-1	10	0	0	400	295	295
Comparative Example 1-2	0	0	100	400	250	250
Comparative Example 1-3	0	10	90	400	250	250
Comparative Example 1-4	25	0	50	425	250	250
Comparative Example 1-5	3	0	150	400	223	224
Comparative Example 1-6	10	0	90	650	0	250
Comparative Example 1-7	10	0	90	0	650	250

<실험예 1. 항진균 효과 확인>Experimental Example 1. Confirmation of antifungal effect

Trichophyton rubrum ( KCTC 6345), Trichophyton mentagrophytes (KCTC 6077), Microsporum canis (KCTC 6348) from the Korean Collection for Type Cultures (KCTC) 4 Candida albicans (KCTC 7965) were distributed and their inhibitory activity was assayed by paper disc diffusion method.

First, 40 g of dextrose and 10 g of peptone were mixed to add 1 L of water and heated and sterilized to prepare SDB (Saboraud dextrose broth) medium, and 15 g of agar (agar) in the same composition. SDA (Saboraud dextrose agar) was prepared by adding (40 g dextrose, 10 g peptone, agar 15 g, water 1 g in total). Subsequently, the cultured strains were inoculated into the SDB medium and incubated at 28 ° C. for 7 days (however, Candida albicans was cultured daily), and 1 ml of each culture solution and 2 ml of soft agar (0.7%) were added. Mix evenly and spread on SDA medium. After inoculation in SDA medium, paper discs treated with 10, 20 and 50 μl of the compositions of Example 1 and Comparative Example 1 were placed on a medium inoculated with each bacterium and incubated for 14 days at 28 ° C. ( However, Candida albicans is cultured daily). Antifungal activity was confirmed by looking at the size of the clear zone formed around the margin, and the results are shown in Table 3 below. At this time, the size of the growth inhibition ring due to each composition was determined to have an antifungal activity in 10mm or more.

TABLE 3

Condition	Volume applied to paper disc (μl)	Size of low ring (mm)
Condition	Volume applied to paper disc (μl)	Tricophyton rubrum	Trichophyton Mentagrophytes	Micros Forum Canis	Candida albicans
Example 1-1	10	++++	++	++	++
	20	+++++	+++	+++	++
	50	++++++	+++++	++++	++++
Example 1-2	10	+++	++	++	++++
	20	++++	++	++++	+++++
	50	+++++	++++	++++	+++++
Example 1-3	10	+++	++	++	+++
	20	++++	+++	++	++++
	50	+++++	+++	++++	+++++
Example 1-4	10	+++	+++	++	+++
	20	+++	++++	++	+++
	50	++++	++++	++++	++++
Example 1-5	10	++	++	+++	++
	20	++++	+++	++++	+++
	50	++++	++++	++++	+++++
Comparative Example 1-1	10	+	+	+	+
	20	+	+	+	+
	50	++	+	+	+
Comparative Example 1-2	10	+	+	+	+
	20	+	+	+	+
	50	+	+	+	+
Comparative Example 1-3	10	+	+	+	+
	20	+	+	+	+
	50	+	++	+	++
Comparative Example 1-4	10	+	+	+	+
	20	++	+	+	+
	50	+++	++	++	+
Comparative Example 1-5	10	+	+	+	+
	20	+	++	+	+
	50	++	++	+++	++
10 mm or less: +, 10-14 mm: ++, 15-19 mm: +++, 20-24: ++++, 25-30: +++++, 30 mm or more: ++++ ++

Referring to Table 3, the compositions of Example 1 of the present invention are all anti-fungal, as the low ring size for Trichophyton rubrum, Trichophyton mentagrophytes, Microsforum canis, Candida albicans is 10 mm or more. Although it was found to be remarkably excellent, the composition of Comparative Example 1 was found to have little antifungal properties because the size of the non-ring ring for each fungus is remarkably small.

<실험예 2. 무좀 치료 효과 확인> Experimental Example 2 Checking the Athlete's Foot Treatment Effect

After the compositions of Example 1 and Comparative Example 1 were applied to the feet of 7 athlete's foot athletes in each group, contact with water was avoided as much as possible, and each composition was recoated once a day. After 3 days from the first application, the athlete's foot treatment effect of each patient was confirmed based on the 'athlete symptom index' of Table 4 compared with the results before treatment.

The athletes were athletes diagnosed athlete's foot in both hospitals from January 1, 2009 to December 31, 2011, the subjects were confirmed in both men and women and the results are shown in Table 5.

Table 4

Athlete's foot symptom index

1 point: foot odor, keratinization, itching severe, no change before and after treatment / 2 points: foot odor, keratinization and itching are reduced by 20% compared to before treatment / 3 point: foot odor, keratinization and itching compared to before treatment Reduced by 50% / 4 points: Foot odor, keratinization and itching are reduced by 80% compared to before treatment / 5 points: Foot odor, keratinization and itching disappear completely

Table 5

Condition	Athlete's foot symptoms index mean
Example 1-1	4.7
Example 1-2	4.6
Example 1-3	4.5
Example 1-4	4.3
Example 1-5	4.1
Comparative Example 1-1	1.7
Comparative Example 1-2	1.3
Comparative Example 1-3	2.2
Comparative Example 1-4	2.5
Comparative Example 1-5	2.6
Comparative Example 1-6	3.2
Comparative Example 1-7	3.3
Control group	1.0

Referring to the results, it was confirmed that the composition of Example 1 of the present invention is very excellent in athlete's foot treatment. On the other hand, the therapeutic effect of the composition of Comparative Example 1-1, which does not contain undecylenic acid, and the composition of Comparative Example 1-2, which does not contain castor oil extracted with hexane, was very low. The therapeutic effect of the composition using castor oil was also found to be significantly different compared to the composition of Example 1. In addition, even if all the castor oil extracted with undecylenic acid or hexane is included in the content range for preparing the composition of the present invention, it was found that the effect is not high.

In addition, Comparative Examples 1-6 and Comparative Examples 1-7 are propylene glycol and propyl alcohol-free compositions, respectively, even if these components are not included, the antifungal effect was found to be somewhat low. The antifungal effect of the composition of the present invention was determined to be excellent only when all were included, which is expected because propylene glycol or propyl alcohol plays a role in enhancing the skin coating effect.

Claims

Castor oil extracted with hexane, containing 0.5 to 2% by weight of castor oil, 7 to 11% by weight of undecylenic acid, 30 to 50% by weight of propyl alcohol, 15 to 35% by weight of propylene glycol and 15 to 35% by weight of water. The external preparation composition for athlete's foot prevention or treatment.
The method of claim 1,

The composition is a skin external composition for athlete's foot prevention or treatment, characterized in that the pH is adjusted to 6.0 ~ 6.5 by using a triethanolamine solution.
The method of claim 1,

The athlete's foot is derived from a fungus selected from the group consisting of Trichophyton rubrum , Trichophyton mentagrophytes , Microsporum canis and Candida albicans . Athlete's foot external composition for athlete's foot, characterized in that the disease.
(Step 1) mixing the castor pulverized product with normal hexane and stirring at 15 ~ 27 ℃;

(Step 2) collecting the remaining castor oil after removing the solid content from the stirring and separating the remaining hexane by the concentrated vacuum method using a heated bath; And,

(Step 3) 0.5 to 2% by weight of castor oil extracted from the hexane, 7 to 11% by weight undecylene acid, 30 to 50% by weight of propyl alcohol, 15 to 35% by weight of propylene glycol and 15 to 35% by weight of water Mixing and stirring;

Method of producing a composition containing castor oil, undecylenic acid, propyl alcohol, propylene glycol, and water, which is cast through hexane, characterized in that it is prepared through.
The method of claim 4, wherein

When the mixture is stirred in step 3, the composition containing castor oil, undecylenic acid, propyl alcohol, propylene glycol, and water extracted with castor is characterized in that the pH is adjusted to 6.0 to 6.5 using a triethanolamine solution. Method of preparation.