Cleansing agent to prevent vaginal candidiasis

Abstract

To provide a cleansing agent which has a strong bactericidal effect against Candida albicans, has little effect on other normal bacteria, and can be preferably used by pregnant women, and is effective in preventing and recurring vaginal diseases caused by Candida albicans. [Solution] A cleaning agent comprising saponin derived from sea cucumber, water as a base solvent, and a surfactant, wherein the content of holotoxins in the saponin in the cleaning agent is 25 ppm or more, and the surfactant comprises a lauric acid-based surfactant which is a derivative of lauric acid, but does not comprise an oleic acid-based surfactant which is a derivative of oleic acid.

Description

[Technical field]

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

[0002] For example, for women, vaginal diseases are common problems, such as bacterial vaginosis and vulvovaginal candidiasis, which cause both mental distress and physical discomfort. Vulvovaginal candidiasis is diagnosed when Candida albicans, the most common fungus of the Candida genus, is detected in the vulva or vagina, and symptoms such as itching and increased vaginal discharge and inflammation of the vulva or vagina are observed. 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 and are present in small numbers on the skin and digestive mucosa. They are not usually harmful to the human body, but they can overgrow under certain conditions and cause infectious symptoms. For example, oral administration of antibiotics, use of steroids and immunosuppressants, weakened immunity, and diabetes are the main factors that cause Candida albicans to overgrow and cause infectious symptoms. In particular, pregnant women have a weakened immune system so that the mother does not reject the fetus. In particular, pregnant women in the middle to late stages of pregnancy are more likely to have a weakened immune system and to have more vaginal discharge due to an increase in the female hormone estrogen. This makes them more susceptible to the proliferation of Candida fungi.

[0004] As a result, 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 for bacterial vaginosis and vaginitis caused by Candida albicans have the problem of causing side effects because they also attack other normal vaginal bacteria. In addition, the use of antifungal drugs is often contraindicated or undesirable for pregnant women, so there is a demand for the development of a method of countermeasures against vulvovaginal candidiasis without using drugs.

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

[0008] The present invention has been proposed in consideration of the above points, and an object of the present invention is, in one aspect, to provide a cleansing agent that has strong bactericidal activity against Candida albicans, has little effect on other normal flora, and can be preferably used 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 cleaning agent wherein the surfactant 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. Effect of the Invention

[0010] According to an embodiment of the present invention, in one aspect, a cleansing agent can be provided which has a strong bactericidal effect against Candida albicans, has little effect on other normal flora, and can be preferably used by pregnant women, and is effective in preventing and recurring vaginal diseases caused by Candida albicans. [Brief description of the drawings]

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

[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) contained in sea cucumber, a useful ingredient that has a bactericidal effect against fungi such as Candida, but has little bactericidal effect against resident bacteria, into a cleanser, it is possible to provide a cleanser that has a strong bactericidal effect against fungi (Candida albicans) and 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 a bactericidal effect against fungi such as Candida and yeast, and to have little effect on the proliferation of other normal bacteria (see, for example, Patent Document 1), and frondoside A is known to have an anticancer effect that suppresses the proliferation of cancer cells. For this reason, products that utilize the functions of sea cucumber saponins and have been put into practical use include sea cucumber soap that utilizes its surfactant effect and athlete's foot treatment drugs that utilize the bactericidal effect of fungi. However, no cleansers for women's vaginal diseases that utilize the functions of sea cucumber saponins have been developed.

[0016] The reasons for this include the following: for female vaginal diseases, conventional antifungal drugs and antibiotics are highly effective in eradicating acute infections, but have little effect in preventing infections and recurrences, and it was unclear whether sea cucumber saponin could prevent infections and recurrences; when sea cucumber saponin is mixed with conventional cleansing agents, the bactericidal action of sea cucumber saponin against Candida albicans may be inhibited; when sea cucumber saponin is mixed with conventional cleansing agents, the growth of other resident bacteria may be inhibited; and because a method for extracting sea cucumber extract with a constant sea cucumber saponin content had not been established, quantitative verification of, for example, how much sea cucumber extract should be used could not be carried out.

[0017] It has been discovered that the cleaning agent of this embodiment, even though it contains a holotoxin group derived from sea cucumber, can prevent infectious diseases and recurrence, has a bactericidal effect against Candida fungi, does not inhibit the growth of resident bacteria, and can maintain a stable and 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] (Ingredient of cleaning agent - sea cucumber saponin derived from sea cucumber) The cleaning agent according to the present embodiment contains sea cucumber-derived sea cucumber saponin, which has a holotoxin concentration of 25 ppm or more in the cleaning agent. By making the holotoxin concentration in the cleaning agent 25 ppm or more, when the cleaning agent is mixed with a surfactant described below, the cleaning agent can inhibit the biofilm formation of Candida albicans at a statistically significant level without inhibiting the bactericidal action of each of them against fungi.

[0020] As a method for extracting sea cucumber saponin from sea cucumber, it is preferable to use 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 sea cucumber saponin at a constant ratio even when the content of sea cucumber saponin varies greatly depending on individual differences of sea cucumbers, production area, collection time, 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 the present embodiment preferably contains a lauric acid surfactant, which is a derivative of lauric acid, and does not contain an oleic acid surfactant, which is a derivative of oleic acid. Although the reason is unclear in many respects, the interaction between the lauric acid surfactant and sea cucumber saponin can suppress the growth of Candida fungi without inhibiting the bactericidal action of each other against fungi, while when an oleic acid surfactant and sea cucumber saponin are used, the oleic acid surfactant inhibits the growth inhibitory effect of the holotoxin against Candida albicans.

[0025] As described above, for example, for pregnant women, it is preferable to use naturally derived ingredients that are less irritating and less damaging to the human body. Generally, sodium salts or potassium salts are known as basic salts of fatty acids, and both have been confirmed to be less irritating to the human body, but potassium salts are generally said to be less irritating. Therefore, potassium laurate can be particularly preferably used as the surfactant component used in this embodiment among lauric acid surfactants. Furthermore, as the lauric acid surfactant according to this embodiment, it is preferable to use a derivative of lauric acid derived from coconut oil and / or palm kernel oil, and it is particularly preferable to use potassium laurate obtained from lauric acid derived from hydrolysis of nut oil such as coconut oil and / or palm kernel oil and a potassium compound (such as potassium hydroxide). The amount of surfactant in the cleaning agent according to this embodiment is usually 10% by mass 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, since the skin of a woman's delicate zone is thinner than that of the eyelids, is vulnerable to external stimuli, and is prone to drying, and a dry environment is an environment in which resident bacteria do not easily proliferate, it is preferable for the cleanser to contain a moisturizer component.

[0027] As moisturizing agents in the cleaning agent according to the present embodiment, aloe vera juice, honey, althea root extract, chamomile flower extract, and nettle leaf extract are used. The amount of moisturizing agent in the cleaning agent according to the present embodiment is usually 1% by mass to 10% by mass.

[0028] The fragrances used in the cleaning agent 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 embodiment, a cleaning agent containing citric acid as a fragrance and a pH adjuster, tocopherol as an antioxidant and a fragrance, and potassium sorbate as a fragrance and a 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 the present embodiment, an example is described in which it is confirmed that the content of holotoxins in saponin is preferably 25 ppm or more. More specifically, an example is described in which it is confirmed that the content of holotoxins in saponin is 25 ppm or more, thereby providing a bactericidal effect against Candida albicans.

[0032] Candida albicans SC5314 was attached to the plate surface for 2 hours at 37℃ using RPMI supplemented with MOPS as the mycelium induction medium. After rinsing for 10 minutes with a detergent containing a specified amount of sea cucumber-derived holotoxins (HTXs), RPMI medium was added and the plate was cultured at 37℃ for 24 hours to form 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] Thereafter, the medium was replaced with RPMI medium supplemented with 10% AlamerBlue (registered trademark) and incubated for 1 hour at 37° C. Then, the absorbance at 570 nm to 600 nm was measured using a microplate reader to calculate the OD value, thereby evaluating the biofilm forming ability.

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

[0036] Figure 1 shows a graph showing biofilm activity for each cleaning condition. As shown in Figure 1, when washing with a cleaning agent containing 2.5 ppm of the holotoxin group (25 ppm relative to the cleaning agent), biofilm formation can be more efficiently inhibited than when washing with a cleaning agent containing no holotoxin group alone. In addition, when washing with a cleaning agent containing 2.5 ppm of the holotoxin group, the P value was 0.05 or less compared to when washing with the holotoxin group alone, and it was found that there was a statistically significant difference.

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

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

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

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

[0041] The horizontal axis of Figure 3 represents the concentration in the medium (0% (no addition), 0.025%, 0.05%, 0.1%) when 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. As is clear from the results in Figure 3, the growth of Candida albicans can be inhibited by adding potassium laurate at a certain concentration or higher (in the examples, 0.025% or higher 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 is 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 is 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 of Figures 2, 3, 4, and 5, when holotoxin and potassium laurate were mixed, they did not inhibit each other's growth inhibitory effect on 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 inhibiting the antifungal action of each other.

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

[0046] Furthermore, the cleaning agent 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 cleaning agent that is gentle on the skin and less irritating even for pregnant women.

[0047] Although the embodiments of the present invention have been described above based on the drawings, the specific configuration should not be considered to be limited to these embodiments. The scope of the present invention is indicated 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. An anti-Candida cleanser 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 surfactant includes a lauric acid-based surfactant which is a derivative of lauric acid, but does not include an oleic acid-based surfactant which is a derivative of oleic acid, The amount of the surfactant is 10% by mass to 30% by mass based on the cleaning agent, A cleaning agent, wherein the lauric acid-based surfactant is potassium laurate.

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 agents include 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 moisturizer is 1% by mass to 10% by mass relative to the cleaning agent. The cleaning agent according to claim 3.

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