Cleansing agent to prevent vaginal candidiasis

Abstract

To provide a cleansing agent effective in the prevention and recurrence of vaginal diseases caused by Candida albicans, which has a strong bactericidal effect against Candida albicans and has little effect on other normal flora and can be suitably used by pregnant women.SOLUTION: Provided is a cleaning agent comprising a saponin derived from Holothuroidea, water as a base solvent, and a surfactant, a content of a holotoxin group in the saponin relative to the cleaning agent being 25 ppm or more, and the surfactant including a lauric acid-based surfactant which is a derivative of lauric acid, but not including an oleic acid-based surfactant which is a derivative of oleic acid.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a cleanser for preventing or combating vulvovaginitis of fungal origin of the Candida genus. [Background technology]

[0002] For example, vaginal diseases are common problems for women, and bacterial vaginosis and vulvovaginal candidiasis, for example, cause both psychological distress and physical discomfort. Vulvovaginal candidiasis is diagnosed when Candida albicans, the most common fungus in the Candida genus, is detected in the vulva or vagina, resulting in subjective symptoms such as itching and increased vaginal discharge, as well as inflammation of the vulva or vagina. Bacterial vaginosis and vaginitis caused by Candida albicans are said to account for approximately 90% of acute and chronic inflammation of the female reproductive tract.

[0003] Candida fungi are normal inhabitants of the human body, present in small numbers on the skin and gastrointestinal mucosa. While they are not normally harmful to the human body, they can overgrow and cause infectious symptoms under certain conditions. For example, oral antibiotic use, steroid or immunosuppressant use, a weakened immune system, or diabetes are major factors that can cause the proliferation of Candida albicans, resulting in infectious symptoms. Pregnant women, in particular, have a weakened immune system to prevent the mother from rejecting the fetus. Women in the mid- to late stages of pregnancy are particularly susceptible to Candida overgrowth due to their significantly weakened immune system and increased levels of the female hormone estrogen, which can lead to increased vaginal discharge.

[0004] Therefore, various antifungal and antibiotic drugs are used to treat vaginal diseases and restore healthy vaginal flora. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6977940 specification Summary of the Invention [Problem to be solved by the invention]

[0006] However, conventional antifungal and antibiotic drugs used to treat bacterial vaginosis and vaginitis caused by Candida albicans have the problem of causing significant side effects because they also attack other normal vaginal flora. Furthermore, the use of antifungal drugs is often contraindicated or undesirable for pregnant women, so there is a need to develop a drug-free method of treating vulvovaginal candidiasis.

[0007] Furthermore, although the above-mentioned conventional antifungal drugs and antibiotics are highly effective in eradicating acute infections, they also have the problem of being less effective in preventing infections and recurrence.

[0008] The present invention has been proposed in view of the above points, and one object of the present invention is to provide a cleanser that has strong bactericidal activity against Candida albicans, has little effect on other normal flora, and is suitable for use by pregnant women, and is effective in preventing and recurring vaginal diseases caused by Candida albicans. [Means for solving the problem]

[0009] A cleaning agent comprising: Saponin derived from sea cucumber, Water as the base solvent, A surfactant, Including, The content of the holotoxin group in the saponin in the cleaning agent is 25 ppm or more, The detergent contains a lauric acid-based surfactant, which is a derivative of lauric acid, but does not contain an oleic acid-based surfactant, which is a derivative of oleic acid. [Effects of the Invention]

[0010] According to an embodiment of the present invention, in one aspect, a cleanser can be provided that has strong bactericidal activity against Candida albicans, has little effect on other normal flora, and is suitable for use by pregnant women, and is effective in preventing and recurring vaginal diseases caused by Candida albicans. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a graph showing biofilm activity for each washing condition. [Figure 2] FIG. 2 is a schematic diagram illustrating the inhibitory effect of holotoxin on the growth of Candida albicans. [Figure 3] FIG. 3 is a schematic diagram illustrating the inhibitory effect of fatty acid potassium on the proliferation of Candida albicans. [Figure 4] FIG. 4 is a schematic diagram illustrating the interaction between potassium laurate and holotoxin. [Figure 5] FIG. 5 is a schematic diagram illustrating the interaction between potassium oleate and holotoxin. DETAILED DESCRIPTION OF THE INVENTION

[0012] The cleaning agent according to this embodiment will be described in detail below.

[0013] By carefully examining various useful ingredients that are effective in improving diseases, the inventors have found that by incorporating a glycoside (saponin) found in sea cucumber, which is a useful ingredient that has a bactericidal effect against fungi such as Candida but has little bactericidal effect on resident bacteria, into a cleanser, it is possible to provide a cleanser that has strong bactericidal activity against fungi (Candida albicans) but has little effect on other resident bacteria, and is effective in preventing and recurring vaginal diseases caused by Candida albicans.

[0014] The triterpene glycosides contained in sea cucumber include saponins consisting of the holotoxin group (HTXs), such as holotoxin A, holotoxin B, and holotoxin A1 and holotoxin B1, as well as a saponin called frondoside A (hereinafter referred to as "sea cucumber saponin").

[0015] Among sea cucumber saponins, the holotoxin group is known to have bactericidal activity, particularly against fungi such as Candida and yeast, while having little effect on the growth of other normal flora (see, for example, Patent Document 1), and frondoside A is known to have an anticancer activity that suppresses the growth of cancer cells. Therefore, products that utilize the functions of sea cucumber saponins have been put into practical use, such as sea cucumber soap, which utilizes its surfactant activity, and a treatment for athlete's foot, which utilizes its fungal bactericidal activity. However, no cleanser for female vaginal diseases that utilizes the functions of sea cucumber saponins has been developed.

[0016] The reasons for this include the following: while conventional antifungal drugs and antibiotics are highly effective in eradicating acute infections for women's vaginal diseases, they are less effective in preventing infections and recurrence, and it was unclear whether sea cucumber saponin could also prevent infections and recurrence; when sea cucumber saponin is mixed with conventional cleansers, there is a possibility that the bactericidal action of sea cucumber saponin on Candida albicans may be inhibited; when sea cucumber saponin is mixed with conventional cleansers, there is a possibility that the growth of other resident bacteria may be inhibited; and because there is no established method for extracting sea cucumber extract with a consistent sea cucumber saponin content, quantitative verification of how much sea cucumber extract should be used, etc., has not been carried out.

[0017] It was discovered that the cleaning agent according to this embodiment, even one containing a holotoxin group derived from sea cucumber, can prevent infections and their recurrence, has a bactericidal effect against Candida fungi, does not inhibit the growth of resident bacteria, and can maintain a stable, constant sea cucumber saponin content, leading to the present invention.

[0018] The components of the cleaning agent according to this embodiment are described in detail below.

[0019] (Cleaning agent ingredient - sea cucumber saponin derived from sea cucumber) The detergent according to this embodiment contains sea cucumber-derived sea cucumber saponin, which has a holotoxin concentration of 25 ppm or higher. By adjusting the holotoxin concentration to 25 ppm or higher, when the detergent is mixed with a surfactant (described below), the detergent can inhibit Candida albicans biofilm formation at a statistically significant level without interfering with the fungal bactericidal activity of either surfactant.

[0020] The method for extracting sea cucumber saponin from sea cucumber preferably uses a sea cucumber extract extracted by the method described in Patent Document 1. The method for extracting sea cucumber extract described in Patent Document 1 can obtain a sea cucumber extract containing a constant proportion of sea cucumber saponin, even if the content of sea cucumber saponin varies greatly depending on individual sea cucumbers, the place of origin, the time of collection, etc.

[0021] (Cleaning agent ingredients - base solvent) The cleaning agent according to this embodiment can be produced by mixing a base solvent component, a surfactant component, and, if necessary, other components such as a moisturizer component, a fragrance, a lubricant, and a preservative.

[0022] Purified water was used as the base component in the cleaning agent according to this embodiment.

[0023] The amount of the base component in the cleaning agent according to this embodiment is usually the balance of the other components described below.

[0024] (Cleaning agent ingredients - surfactants) The surfactant according to this embodiment preferably contains a lauric acid surfactant, which is a derivative of lauric acid, but does not contain an oleic acid surfactant, which is a derivative of oleic acid. While the reason for this is unclear, the interaction between the lauric acid surfactant and sea cucumber saponin allows the growth of Candida to be inhibited without interfering with the antifungal activity of each other, whereas when an oleic acid surfactant and sea cucumber saponin are used, the oleic acid surfactant inhibits the growth-inhibitory effect of the holotoxin on Candida albicans.

[0025] As mentioned above, it is preferable to use naturally derived ingredients that are less harmful to the human body and less irritating, for example, for pregnant women. Generally, sodium salts and potassium salts are known as basic salts of fatty acids, and both have been confirmed to be less harmful to the human body, but potassium salts are generally considered to be less irritating. Therefore, potassium laurate is particularly preferably used as the surfactant component for use in this embodiment, among lauric acid surfactants. Furthermore, as the lauric acid surfactant for this embodiment, a derivative of lauric acid derived from coconut oil and / or palm kernel oil is preferably used, and potassium laurate obtained from lauric acid derived from the hydrolysis of nut oils such as coconut oil and / or palm kernel oil and a potassium compound (such as potassium hydroxide) is particularly preferred. The amount of surfactant in the cleanser for this embodiment is typically 10% to 30% by mass.

[0026] (Cleaning agent ingredients - Other ingredients) The cleanser according to this embodiment may contain other ingredients such as moisturizers and fragrances, and in particular, it is preferable to include a moisturizer component, since the skin in a woman's delicate area is thinner than that of the eyelids, is more susceptible to external stimuli, and is prone to dryness, and a dry environment makes it difficult for resident bacteria to grow.

[0027] The moisturizing agents used in the cleanser according to this embodiment include aloe vera juice, honey, Althea root extract, chamomile flower extract, and nettle leaf extract. The amount of moisturizing agent in the cleanser according to this embodiment is usually 1% by mass to 10% by mass.

[0028] The fragrances used in the cleanser according to this embodiment include pelargonium graveolens leaf oil, damask rose flower oil, jojoba seed oil, palmarosa oil, ylang-ylang flower oil, lavender oil, lemon peel oil, jasmine flower oil, and cinnamon leaf oil.

[0029] In this example, a detergent containing citric acid as a fragrance and pH adjuster, tocopherol as an antioxidant and fragrance, and potassium sorbate as a fragrance and preservative was used.

[0030] The content of other components in the cleaning agent according to this embodiment is usually 5% by mass or less.

[0031] Example 1 In the cleaning agent according to this embodiment, an example is described in which it is confirmed that the holotoxin content in the saponin is preferably 25 ppm or more. More specifically, an example is described in which it is confirmed that the holotoxin content in the saponin is 25 ppm or more, thereby imparting bactericidal activity against Candida albicans.

[0032] Candida albicans SC5314 was grown on a plate using RPMI supplemented with MOPS as a mycelium induction medium at 37°C for 2 hours. The plate was then rinsed for 10 minutes with a detergent containing a specified amount of sea cucumber-derived holotoxins (HTXs). RPMI medium was then added and the plate was incubated at 37°C for 24 hours to allow the formation of a Candida albicans biofilm.

[0033] The blending ratio of the detergent was adjusted to 90-100% medium and 0-10% detergent, with the amount of holotoxin being 0 ppm-2.5 ppm relative to the total.

[0034] The medium was then replaced with RPMI medium supplemented with 10% AlamerBlue (registered trademark) and incubated for 1 hour at 37° C. The biofilm-forming ability was evaluated by measuring the absorbance at 570 nm to 600 nm using a microplate reader and calculating the OD value.

[0035] In addition, the formation of biofilms was photographed using an electron microscope at 100x magnification.

[0036] Figure 1 shows a graph showing biofilm activity under each cleaning condition. As shown in Figure 1, biofilm formation was more efficiently inhibited when the samples were washed with a detergent containing 2.5 ppm of holotoxin (25 ppm relative to the detergent) than when the samples were washed with a detergent containing only holotoxin. Furthermore, the P value of the results for the samples washed with a detergent containing 2.5 ppm of holotoxin was less than 0.05, indicating a statistically significant difference compared to when the samples were washed with only holotoxin.

[0037] Example 2 Next, we will explain an example in which it was confirmed that by using potassium laurate as a surfactant, the interaction between the surfactant and sea cucumber saponin can suppress the growth of Candida fungi without inhibiting the antifungal action of each other.

[0038] Candida albicans SC5314 strain was cultured overnight at 30°C in Sabouraud medium supplemented with chloramphenicol (CP). The culture was then diluted 100-fold with medium, and the samples described below were added. The culture was then cultured in a 96-well plate at 30°C for 20-24 hours. The growth of Candida albicans was then quantified by measuring the absorbance at 600 nm.

[0039] Figure 2 shows a schematic diagram illustrating the inhibitory effect of holotoxin on the growth of Candida albicans. Figure 3 shows a schematic diagram illustrating the inhibitory effect of potassium fatty acid on the growth of Candida albicans. Figure 4 shows a schematic diagram illustrating the interaction between potassium laurate and holotoxin. Figure 5 shows a schematic diagram illustrating the interaction between potassium oleate and holotoxin.

[0040] The horizontal axis of Figure 2 represents the concentration (0 ppm (no addition), 1 ppm, 2 ppm, 4 ppm) in the medium when holotoxin was selected as the sample to be added, and the vertical axis represents the cell growth rate of Candida albicans. As is clear from the results in Figure 2, it was found that the growth of Candida albicans can be suppressed by adding holotoxin at a certain concentration or higher (in the examples, a concentration of 2 ppm or higher in the medium).

[0041] The horizontal axis of Figure 3 represents the concentration (0% (no addition), 0.025%, 0.05%, 0.1%) of potassium laurate or potassium oleate in the medium when the sample to be added is selected, and the vertical axis represents the cell growth rate of Candida albicans. As is clear from the results in Figure 3, the growth of Candida albicans can be suppressed by adding potassium laurate at a certain concentration or higher (in the examples, 0.025% or higher relative to the medium), whereas the addition of potassium oleate did not suppress the growth of Candida albicans within the concentration range of the examples.

[0042] The vertical axis of Figure 4 represents the concentration of potassium laurate or potassium oleate in the medium (0% (no addition), 0.025%, 0.05%, 0.1%) when a mixture of 1 ppm holotoxin and potassium laurate or potassium oleate was selected as the sample to be added, and the vertical axis represents the cell growth rate of Candida albicans. The vertical axis of Figure 5 represents the concentration of potassium laurate or potassium oleate in the medium (0% (no addition), 0.025%, 0.05%, 0.1%) when a mixture of 2 ppm holotoxin and potassium laurate or potassium oleate was selected as the sample to be added, and the vertical axis represents the cell growth rate of Candida albicans.

[0043] As is clear from the results in Figures 2, 3, 4, and 5, when holotoxin and potassium laurate were mixed, they did not inhibit each other's growth inhibition of Candida albicans, whereas when holotoxin and potassium oleate were mixed, potassium oleate inhibited the growth inhibitory effect of holotoxin on Candida albicans.

[0044] It has been found that the cleaning agent of this embodiment contains sea cucumber saponin derived from sea cucumber and potassium laurate as a surfactant, and that the interaction between the surfactant and sea cucumber saponin can suppress the growth of Candida fungi without interfering with each other's antifungal activity.

[0045] Furthermore, the cleaning agent according to this embodiment uses sea cucumber saponin derived from sea cucumber, which has a strong bactericidal effect against fungi (Candida albicans) and has little effect on other resident bacteria.

[0046] Furthermore, the cleanser according to this embodiment uses, as a surfactant, lauric acid derived from the hydrolysis of nut oils such as coconut oil and / or palm kernel oil, and potassium laurate obtained from a potassium compound, making it a cleanser that is gentle and non-irritating, even for pregnant women.

[0047] Although the embodiments of the present invention have been described above with reference to the drawings, the specific configurations should not be considered to be limited to these embodiments. The scope of the present invention is defined not only by the description of the above embodiments but also by the claims, and further includes all modifications within the meaning and scope of the claims.

Claims

1. A cleaning agent comprising: Saponin derived from sea cucumber, Water as the base solvent, A surfactant, Including, The content of the holotoxin group in the saponin in the cleaning agent is 25 ppm or more, The detergent contains a lauric acid-based surfactant, which is a derivative of lauric acid, but does not contain an oleic acid-based surfactant, which is a derivative of oleic acid.

2. The lauric acid is obtained by hydrolysis of coconut oil and / or palm kernel oil. The cleaning agent according to claim 1.

3. The cleanser further comprises a moisturizer; The moisturizing agent includes aloe vera juice, honey, althea root extract, chamomile flower extract, and nettle leaf extract. The cleaning agent according to claim 1.

4. The amount of the surfactant is 10% by mass to 30% by mass relative to the cleaning agent, The amount of the moisturizing agent is 1% by mass to 10% by mass relative to the cleanser. The cleaning agent according to claim 3.

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