JP7281729B2 - antifungal composition - Google Patents

Description

The present invention relates to antifungal compositions.

Antifungal drug administration, photochemical therapy, and the like are used as measures against mycoses. However, it is known that mycoses are more difficult to treat than bacterial infections because fungi have a rigid cell wall made of chitin and are eukaryotes like humans.

Antifungal agents conventionally used for the treatment of mycoses as internal antifungal agents include, for example, polyenes, fluoropyridines, imidazoles (azoles), and the like.
In addition, antifungal agents such as azoles have been used to suppress antifungals such as Candida. However, there are concerns about the side effects of antifungal agents and the problem of drug resistance caused by long-term administration.
Therefore, Patent Document 1 discloses an antifungal agent characterized by containing an azole antifungal substance and lactoferrin as active ingredients for the purpose of providing an antifungal agent exhibiting a strong antifungal action at a low concentration. disclosed.

JP-A-9-2970

Bacteria and fungi are clearly different in cell internal structure and physiological functions, so it is difficult to say that antibacterial ingredients always exhibit antifungal effects. It is said that it is difficult to find a component that damages only human tissue and has few side effects on human tissue. However, antifungal compositions with as few side effects as possible are desired.
Therefore, the main object of the present technology is to provide a highly safe antifungal composition.

The inventors of the present invention have studied various antifungal components, and as shown in [Examples] below, have found that lactoferrin (hereinafter also referred to as "LF") alone has almost no antifungal action. In addition, we obtained the knowledge that the LPO reaction system alone does not have almost any antifungal action.

However, the present inventors have found that the antifungal action can be dramatically enhanced by combining the LF and LPO reaction systems, which each have little antifungal action. Furthermore, the present inventors have found that even if the concentration of the LF and LPO reaction systems used is reduced, a high metabolic capacity suppression rate can be maintained.

Moreover, since both the LF and LPO reaction systems have different chemical structures from those of the azole system having antifungal action, it was completely unexpected for the present inventors that this combination could dramatically enhance the antifungal action. rice field. Since both the LF and LPO reaction systems are ingredients that are also used as food ingredients, they are both ingredients that are highly safe in terms of dietary experience and can be ingested for a long period of time.

In the present technology, a composition containing at least lactoperoxidase, glucose oxidase and glucose is also referred to as "LPO composition". Further, in the present technology, an enzymatic reaction system by using lactoperoxidase, glucose oxidase and glucose in the presence of thiocyanic acid or a salt thereof is also referred to as "LPO reaction system", and lactoperoxidase, glucose oxidase and glucose are referred to as " Also called "LPO reaction system component". In the present technology, thiocyanic acid or a salt thereof may be present in the application area, and thiocyanic acid or a salt thereof may be included in the composition of the present technology.

Further, in the present technology, the LPO reaction system is one of the hypothiocyanite production systems, and the hypothiocyanite production system includes, for example, an LPO reaction system, a myeloperoxidase system (neutrophils), a hose A radish peroxidase system (horseradish) and the like are known. In the present technology, a system that produces OSCN-: hypothiocyanite is referred to as a "hypothiocyanite production system".

As described above, although there are technical difficulties in finding a highly safe antifungal composition, the present inventors have developed LF and hypothiocyanite-producing The present invention was completed by newly discovering the combined use of the system (preferably the LPO reaction system).
That is, the present invention is as follows (1) to ( 6 ).

(1) An antifungal composition containing lactoferrin and an LPO reaction system as active ingredients and used in the presence of thiocyanic acid or a salt thereof.
(2 ) An antifungal composition containing lactoferrin , lactoperoxidase, glucose oxidase and glucose as active ingredients and used in the presence of thiocyanic acid or a salt thereof.
( 3 ) The composition is a drug, quasi-drug, cosmetic, or sanitary product (provided, however, that quasi-drugs applied to the oral cavity, cosmetics to be applied to the oral cavity, and sanitary products to be applied to the oral cavity) excluding), the composition according to (1) or (2) above.
( 4 ) The drug is a formulation for oral administration, a formulation for oral cavity administration, a formulation for administration by injection, a formulation for dialysis, a formulation for bronchi/lungs, a formulation for administration to the eye, a formulation for administration to the ear, The composition according to ( 3 ) above, which is a nasal formulation, a rectal formulation, a vaginal formulation, or an external formulation.
( 5 ) The composition according to (1) or (2) above, which is a food, drink, feed, or a composition to be applied to the oral cavity (excluding pharmaceuticals to be applied to the oral cavity).
( 6 ) The composition according to ( 5 ) above, wherein the composition applied in the oral cavity is a quasi-drug applied in the oral cavity, a cosmetic product applied in the oral cavity, or a sanitary product applied in the oral cavity. thing.

According to the present technology, a highly safe antifungal composition can be provided. Note that the effects described here are not necessarily limited, and may be any of the effects described in the present technology.

Microscopic observation of morphological changes in Candida albicans due to LF and/or LPO reaction system.

Next, preferred embodiments of the present technology will be described. However, the present technology is not limited to the following preferred embodiments, and can be freely modified within the scope of the present technology. In this specification, percentages are indicated by mass unless otherwise specified.

Use of the technology may be for therapeutic or non-therapeutic purposes.
"Non-therapeutic purposes" is a concept that does not include medical procedures, that is, procedures that treat the human body with therapy.
"Prevention" means preventing or delaying the onset of a disease or condition in a subject, or reducing the risk of a disease or condition in a subject.
"Amelioration" refers to ameliorating a disease, symptom or condition; preventing or slowing deterioration; reversing, preventing or slowing progression.

In this technology, "pharmaceuticals" means pharmaceuticals defined in Article 2, Paragraph 1 of the Law Concerning Securing Quality, Efficacy and Safety of Pharmaceuticals and Medical Devices (hereinafter referred to as the Pharmaceuticals and Medical Devices Law), i.e. , means the items listed in the following items 1 to 3.
(1) Items listed in the Japanese Pharmacopoeia (2) Items intended for use in the diagnosis, treatment or prevention of diseases in humans or animals, such as mechanical instruments (machine instruments, dental materials, medical supplies) , sanitary goods and programs (meaning commands to a computer that are combined so as to obtain a single result; the same shall apply hereinafter) and recording media on which these are recorded; the same shall apply hereinafter) Products (excluding quasi-drugs and regenerative medicine products)
(iii) Items that are intended to affect the structure or function of the body of humans or animals and that are not mechanical devices, etc. (excluding quasi-drugs, cosmetics, and regenerative medicine products)

In addition, in this technology, each formulation that corresponds to "pharmaceuticals", excluding "external preparations", is classified as described in the section "General rules for formulations [3] Articles for formulations" of the "17th revision of the Japanese Pharmacopoeia". A "topical formulation" is a formulation intended for use by applying it to the exterior of the body (eg, the skin (including the scalp) or nails).

In this technology, "quasi-drugs" means quasi-drugs defined in Article 2, Paragraph 2 of the Pharmaceutical and Medical It means that the action on
(i) Items used for the purposes listed in the following (a) through (c) (in addition to these purposes, items used for the purposes specified in Article 2, Paragraph 1, Item 2 or 3): Prevention of nausea and other discomfort, bad breath or body odor, b. Prevention of heat rash, sores, etc. c. Prevention of hair loss, hair growth, or hair removal. Items used for the purpose of controlling rats, flies, mosquitoes, fleas and other similar organisms (in addition to this purpose of use, Article 2, Paragraph 1, Item 2 or 3) 3. Items used for the purposes specified in Article 2, Paragraph 1, Item 2 or 3 (excluding those listed in the following items.) specified by the Minister of Health, Labor and Welfare

In addition, in the present technology, "cosmetics" means cosmetics defined in Article 2, Paragraph 3 of the Pharmaceuticals and Medical Devices Law, that is, cosmetics that cleanse, beautify, increase attractiveness, and enhance the appearance of the human body. Substances that are intended to be applied to the body by rubbing, spraying, or similar methods to change or maintain healthy skin or hair, and that have mild effects on the human body (however, these In addition to the purpose of use, items and quasi-drugs that are also intended to be used for the purposes stipulated in Article 2, Paragraph 1, Item 2 or 3).
In addition, in the present technology, "sanitary products" mean items used for maintaining hygiene (excluding pharmaceuticals, quasi-drugs, and cosmetics).

Furthermore, in the present technology, “applying to the oral cavity” means an aspect in which the oral cavity or the pharynx is the application site.

Examples of the hypothiocyanate system of the present technology include the LPO reaction system, myeloperoxidase system (neutrophils), horseradish peroxidase system (horseradish), and the like. Among these, the LPO reaction system is preferable from the viewpoint of the examples described later.

The hypothiocyanite production system of the present technology is preferably used in the presence of thiocyanic acid or a salt thereof. As for the "thiocyanic acid or salt thereof", the configuration of the LPO composition or LPO reaction system described later can be appropriately adopted.
In addition, the pH for expressing the antifungal action in the lactoferrin and hypothiocyanite production system of the present technology, the amount of various components used, the method of expressing the antifungal action, or the lactoferrin and hypothiocyanite production system of the present technology As for the dosage, usage, etc., the configuration of the LPO composition (LPO reaction system) described later can be appropriately employed.

The present technology is preferably an antifungal composition comprising lactoferrin, lactoperoxidase, glucose oxidase and glucose.
Also, the composition is preferably an antifungal composition used in the presence of thiocyanic acid or a salt thereof.
In addition, the present technology is preferably a composition containing lactoferrin as an active ingredient and enhancing the antifungal action of the LPO reaction system.
Furthermore, the present technology is also preferably a composition that enhances the antifungal action of lactoferrin, containing lactoperoxidase, glucose oxidase, and glucose as active ingredients.

"LPO composition" or "LPO reaction system component" is more suitable for combined use with lactoferrin of the present technology.

Lactoferrin used in the present technology is an iron-binding glycoprotein present in milk, tears, saliva, blood, etc.; lactoferrin separated by chromatography, etc.) (hereinafter also referred to as “isolated lactoferrin”); apo-lactoferrin obtained by deironizing the isolated lactoferrin with an acid (e.g., hydrochloric acid, citric acid, etc.); metal-saturated lactoferrin chelated with zinc, manganese, etc.); lactoferrin saturated with metals at various degrees of saturation;
As the lactoferrin used in the present technology, apolactoferrin, natural lactoferrin, and hololactoferrin are preferable, and natural lactoferrin and/or apolactoferrin are more preferable.
You may select and use 1 type(s) or 2 or more types from these.

In the present technology, lactoferrin is included in milk (colostrum, transitional milk, normal milk, terminal milk, etc.), especially of mammals (eg, bovine, human, sheep, goat, pig, mouse, horse, etc.). Among them, bovine milk, human milk, and the like are preferable in terms of content, availability, and safety.
In the present technology, lactoferrin is not limited to those derived from mammals, and includes recombinant lactoferrin produced from genetically engineered microorganisms, animals, and the like; chemically synthesized lactoferrin, and the like. Lactoferrin may also be non-glycosylated or glycosylated.
Lactoferrin may be commercially available or may be prepared from raw materials such as milk. Commercially available lactoferrin (e.g., Morinaga Milk Industry Co., Ltd., etc.) can be mentioned due to its easy availability, and the method for preparing the isolated lactoferrin is a known preparation method (e.g., Reference 1: JP-A-2014-227375). can be used.

Generally, lactoperoxidase is an oxidoreductase in milk and is known to have the action of catalyzing the production of hypothiocyanite and water from hydrogen peroxide and thiocyanic acid.
Although the lactoperoxidase used in the present technology is not particularly limited, it is preferable to use one derived from mammalian milk. Among the lactoperoxidases, lactoperoxidases derived from milk of cows, horses, sheep, goats, etc. are preferred, and those derived from cow's milk are more preferred.
Since milk has been used for human consumption for many years, milk-derived lactoperoxidase is also highly safe for animals such as humans. Therefore, milk-derived lactoperoxidase is preferred. Furthermore, from the viewpoint of stable productivity, milk-derived lactoperoxidase is more preferable.

The lactoperoxidase can be obtained from milk or the like of the mammal.
The lactoperoxidase used in the present technology is preferably industrially produced from unheated whey such as milk or skim milk according to a conventional method (e.g., ion exchange chromatography, etc.) 5-41981, reference 3: WO2005/078078, etc.).
In addition, commercially available natural product-derived lactoperoxidase (e.g., manufactured by Biopol), recombinant lactoperoxidase, expressed and purified recombinant lactoperoxidase (e.g., Reference 4: Biochemical and Biophysical Research Communications, vol. 271, 2000, p.831-836) or commercially available recombinant lactoperoxidase may be used.
Among these, skim milk or whey derived from bovine milk is preferable as a raw material for the lactoperoxidase used in the present technology, because it can be stably obtained in large amounts.

Glucose oxidase is generally known as an enzyme that oxidizes β-D-glucose to produce D-glucono-δ-lactone and hydrogen peroxide.
Glucose oxidase used in the present technology is not particularly limited, but microorganism-derived glucose oxidase is preferable from the viewpoint of quality stability and productivity.
Examples of enzymes derived from microorganisms include enzymes produced by microorganisms such as Aspergillus niger and Penicillium chrysogenum.
The microorganism-derived glucose oxidase can be obtained using a known method for producing a microorganism-derived enzyme. Moreover, a commercially available glucose oxidase may be used, and a commercially available microorganism-derived glucose oxidase (for example, manufactured by Shin Nihon Kagaku Kogyo Co., Ltd., etc.) can be used.

Glucose used in the present technology is not particularly limited, and for example, commercially available glucose (eg, manufactured by Nihon Shokuhin Kako Co., Ltd., etc.) can also be used. Glucose-containing products (eg, isomerized sugar, starch syrup, starch hydrolysates, etc.) may also be used.

This technique is preferably used in the presence of thiocyanic acid or a salt thereof. When using this technology for an application area where thiocyanic acid already exists (for example, in the oral cavity, etc.), thiocyanic acid or a salt thereof may not be added to the application area, and thiocyanic acid or a salt thereof may be added to the application area. It need not be included in the antifungal composition of the art. When adding the said thiocyanic acid or its salt as needed, a commercial item (for example, Merck Millipore company make) can be used. The salt is not particularly limited, and includes alkali metal salts (eg, sodium salts, potassium salts, etc.), iron (III) salts, and the like.

When using this technology for an application area where thiocyanic acid or a salt thereof does not exist, thiocyanic acid or a salt thereof must be separately added to the application area, or thiocyanic acid or a salt thereof can be added to the antifungal composition of the present technology. It is desirable to include it in things.
In addition, when the amount of thiocyanic acid or a salt thereof of the present technology is insufficient in the area to which the present technology is applied, it is desirable to separately add the shortage to the composition or to the application area, or the shortage It is desirable to include thiocyanic acid or a salt thereof in the composition.

In the present technology, it is preferable to use a pH-adjusting component or to include it in the composition from the viewpoint of stable reaction. In addition, in the present technology, optional components may be appropriately used or may be blended in the composition as long as the effects of the present technology are not impaired.
The pH adjusting component used in the present technology is not particularly limited, but the pH when dissolved in an aqueous solvent is preferably 4.0 to 9.0, more preferably 6.0 to 8.0, and still more preferably 7.0 to 8.0. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.
Examples of the pH-adjusting component include inorganic acids, organic acids and salts thereof, and these may be used singly or in combination of two or more. The pH-adjusting component is preferably water-soluble, and commercially available additives and commercially available food additives may be used.
Examples of the inorganic acid include phosphoric acid, nitric acid and sulfuric acid. Examples of the organic acid include citric acid, lactic acid, malic acid, succinic acid, tartaric acid, and glutamic acid. Examples of salts include alkali metal salts (lithium, potassium, sodium, etc.), alkaline earth metal salts (calcium, magnesium, etc.), and the like.
You may use 1 type(s) or 2 or more types in combination selected from the group of the said pH control component.

The content of lactoferrin in the composition of the present technology is not particularly limited, but the lower limit of the lactoferrin concentration at the time of application is preferably 2 μg/mL or more, more preferably 10 μg/mL or more, more preferably 15 μg/mL or more, and more preferably 15 μg/mL or more. It is suitable to adjust the concentration to preferably 20 μg/mL or more, more preferably 30 μg/mL or more, and still more preferably 50 μg/mL or more. The upper limit of the lactoferrin concentration is preferably adjusted to 10000 µg/mL or less, more preferably 5000 µg/mL or less, and even more preferably 1000 µg/mL or less. The lactoferrin concentration range at the time of application is preferably 2 to 2000 μg/mL, more preferably 8 to 2000 μg/mL, more preferably 30 to 1000 μg/mL, still more preferably 30 to 500 μg/mL, still more preferably 30 to 200 μg. / mL is preferable from the viewpoint of cost and antifungal action. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

Although the content of lactoperoxidase in the present technology is not particularly limited, the lower limit of the lactoperoxidase concentration at the time of application is preferably 0.1 μg/mL or more, more preferably 0.3 μg/mL or more, and more preferably 0 .5 μg/mL or more, more preferably 1.0 μg/mL or more, still more preferably 1.5 μg/mL or more, still more preferably 6 μg/mL or more, still more preferably 10 μg/mL or more is preferred. The upper limit of the lactoperoxidase concentration is preferably adjusted to 1000 μg/mL or less, more preferably 250 μg/mL or less, and even more preferably 100 μg/mL or less. Furthermore, the concentration range is preferably 0.1 to 1000 μg/mL, more preferably 0.5 to 1000 μg/mL, still more preferably 1.5 to 100 μg/mL, still more preferably 1.5 to 50 μg/mL. mL, which is preferable from the viewpoint of cost and antifungal action. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The content of glucose oxidase in the present technology is not particularly limited, but the lower limit of glucose oxidase concentration at the time of application is preferably 0.9 μg/mL or more, more preferably 2.0 μg/mL or more, and more preferably 4.0 μg /mL or more, more preferably 10 µg/mL or more, still more preferably 14 µg/mL or more, and even more preferably 60 µg/mL or more. Also, the upper limit of the glucose oxidase concentration is preferably adjusted to 5000 μg/mL or less, more preferably 1500 μg/mL or less, and even more preferably 1000 μg/mL or less. The range of the glucose oxidase concentration is preferably 0.9 to 1500 μg/mL, more preferably 13 to 1500 μg/mL, still more preferably 14 to 1000 μg/mL, still more preferably 60 to 500 μg/mL, and cost and It is suitable from the viewpoint of antifungal action. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The content of glucose in the present technology is not particularly limited, but the lower limit of the glucose concentration at the time of application is preferably 1 μg/mL or more, more preferably 2 μg/mL or more, preferably 4 μg/mL or more, more preferably 8 μg/mL. mL or more, more preferably 10 μg/mL or more, more preferably 15 μg/mL or more, still more preferably 65 μg/mL or more, and the upper limit of the glucose concentration is preferably 10000 μg/mL or less, and more It is preferably adjusted to 5000 μg/mL or less, more preferably 3000 μg/mL or less. The glucose concentration range is more preferably 10 to 2000 μg/mL, more preferably 15 to 1000 μg/mL, and even more preferably 65 to 500 μg/mL. It is preferable from the point of view and the point of view of improving the antifungal action. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The content of the LPO reaction system component in the present technology is not particularly limited, but the lower limit of the LPO reaction system component concentration at the time of application is preferably 1 μg/mL or more, more preferably 4 μg/mL or more, and more preferably 8 μg/mL. above, more preferably 15 μg/mL or more, still more preferably 20 μg/mL or more, still more preferably 30 μg/mL or more, still more preferably 125 μg/mL or more, and as the upper limit of the LPO reaction system component concentration , preferably 10000 μg/mL or less, more preferably 5000 μg/mL or less, and still more preferably 3000 μg/mL or less. The LPO reaction system component concentration range is preferably 1 to 4000 μg/mL, more preferably 20 to 4000 μg/mL, still more preferably 30 to 2000 μg/mL, and even more preferably 125 to 1000 μg/mL. From the viewpoint of improving the antifungal action, it is preferable to In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The concentration of thiocyanic acid or a salt thereof in the present technology is not particularly limited, but the concentration of thiocyanic acid or a salt thereof at the time of application is preferably 0.1 to 100 mM, more preferably 0.2 to 60 mM, still more preferably 0.3. Adjusting to ~20 mM is preferred. If this concentration is not reached, thiocyanic acid or a salt thereof may be added to the composition or used in the area of use to achieve this concentration. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The content of each active ingredient in the present technology can be designed to provide a suitable application area and application concentration according to its form. The content of each active ingredient in the present technology may be designed, for example, to achieve the concentration in saliva when applied to the oral cavity, or may be designed to achieve the applicable concentration when applied to the skin. good too. In addition, the unit of content of each active ingredient in the present technology may be "μg/mL" as described above, or may be designed according to the dosage form, and may be "μg/g".

Examples of the content of lactoferrin, lactoperoxidase, glucose oxidase and glucose in the antifungal composition of the present technology are given below.
The content of lactoferrin in the composition is preferably 1 to 80% by mass, more preferably 5 to 60% by mass, still more preferably 10 to 40% by mass.
The content of lactoperoxidase in the composition is preferably 0.1 to 50% by mass, more preferably 0.5 to 10% by mass, still more preferably 1 to 5% by mass.
The content of glucose oxidase in the composition is preferably 1 to 60% by mass, more preferably 3 to 30% by mass, still more preferably 5 to 20% by mass.
The content of glucose in the composition may be a sufficient amount as a substrate for glucose oxidase, and is preferably 1 to 60% by mass, more preferably 5 to 50% by mass, still more preferably 10 to 40% by mass. % by mass.
The above upper limit and lower limit of each component can be arbitrarily combined as desired.

In addition, the range of the content of each active ingredient can be appropriately adjusted according to the concentration used when the product form is used.
For example, it is suitable to assume use on the skin or the vagina, etc. Examples of forms of such external skin preparations or pharmaceuticals include washing solutions, spray solutions, tablets, films, etc. It is not limited.
In addition, it is preferable to assume the use of oral care products, and examples of such oral care products include washing liquid, spray liquid, tablets, tablet candy, gum, candy, film, etc., but are not limited to these examples. not something.

The amounts and proportions of each of lactoferrin, lactoperoxidase, glucose oxidase, and glucose used in the present technology are not particularly limited, and the concentrations or contents described above may be combined.

The mass ratio of lactoperoxidase and lactoferrin (lactoperoxidase:lactoferrin) used in the present technology is preferably 1:1000 to 10:1, more preferably 1:100 to 5:1, and still more preferably 1 :50 to 4:1, more preferably 1:20 to 2:1. A ratio of 1:20 to 1:1 is particularly preferred. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The mass ratio of lactoperoxidase and glucose oxidase used in the present technology (lactoperoxidase: glucose oxidase) is preferably 1:1000 to 10:1, more preferably 1:100 to 5:1, and still more preferably is 1:50 to 4:1, more preferably 1:20 to 1:1. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The mass ratio of glucose oxidase to glucose (lactoperoxidase:glucose) used in the present technology is preferably 1:100 to 1:1, more preferably 1:20 to 1:4. More preferably 1:16 to 1:10. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

In the present technology, the mass ratio of lactoperoxidase, glucose oxidase and glucose used (lactoperoxidase:glucose oxidase:glucose) is preferably 1:5 to 10:9 to 16, more preferably 1:8 to 10:9. ~13. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

<Application of this technology>
As shown in [Examples] below, the lactoferrin, lactoperoxidase, glucose oxidase and glucose of the present technology have antifungal action, fungal metabolic capacity inhibitory action, anticandida action and candida activity in the presence of thiocyanic acid or a salt thereof. It has a metabolic capacity suppressing action (hereinafter also referred to as "antifungal action, etc.").
Therefore, the lactoferrin and hypothiocyanite production system of the present technology has antifungal action, fungal metabolic capacity inhibitory action, anticandida action, candida metabolic capacity inhibitory action, and the like.

The lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology can prevent, treat or improve symptoms or diseases (preferably candidiasis) caused by fungi over a long period of time. The present technology can be used in modes such as dermal use, oral administration, ingestion, or oral use.
In addition, the lactoferrin and hypothiocyanite production system (preferably, lactoferrin and LPO reaction system) of the present technology can be used for various applications such as food and drink, feed, cosmetics, external skin care, and oral care. Examples of compositions for this use include food and drink, feed, pharmaceuticals, quasi-drugs, cosmetics, and sanitary products.

In addition, the present technology can be applied to humans and non-human animals (preferably mammals, birds, reptiles, etc.). Among these, humans and pets are preferred, and humans are more preferred. In addition, since each active ingredient of this technology has a long history of food experience and is known to be highly safe, this technology can be applied to people of all ages, including those with reduced physical strength and those with a weak constitution. It is more suitable for the elderly, the elderly and infants.
In addition, although the application site of the present technology is not particularly limited, it can be applied to, for example, skin (for example, stratum corneum nails, etc.), mucous membranes (mucous membranes of eyes, oral cavity, vagina, etc.).

In addition, the lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology can be used for the prevention, treatment, improvement, etc. of mycoses or opportunistic infections. Mycoses include, for example, psoriasis, candidiasis, and the like. Pathogens that cause candidiasis include Candida albicans and the like.

Here, in general, mycoses include superficial mycoses that occur on the skin, mucous membranes, nails, etc., deep skin mycoses that occur in the dermis and subcutaneous tissue, and opportunistic infections in each organ of the whole body, such as the lungs and the intestinal tract. It is broadly classified as a deep-seated mycosis that occurs in
For example, keratinized tissue (e.g., epidermis, hair, nails, etc.), mucosal sites adjacent to skin (e.g., oral cavity, vagina, etc.) and the like are generally known as site of onset with high incidence of mycoses.
Representative mycoses include dermatophytoses (psoriasis) and candidiasis. For example, oral candidiasis, esophageal/intestinal candidiasis, vulvovaginal candidiasis, and the like are generally known as candidiasis.
Other mycoses include aspergillosis, which occurs when spores of fungi of the genus Aspergillus are inhaled and proliferate throughout the body, including in the respiratory tract and blood vessels, ringworm caused by dermatophytes of the genus Trichophyton, and cryptococcus. Cryptococcosis and the like are also commonly known, which are caused by the formation of lesions caused by infection of the lungs or skin by the fungi.

In recent years, as causes of mycosis, for example, the administration of many drugs such as broad-spectrum antibiotics, anticancer drugs, immunosuppressants for organ transplantation, oral contraceptives, and the use of high-calorie infusions and indwelling catheters have been cited. It is becoming possible to
Furthermore, aspiration that occurs when swallowing (swallowing) function is impaired causes pulmonary mycosis or aspiration pneumonia when fungi such as Candida in the oral cavity migrate to the respiratory tract. This aspiration is often seen during eating or drinking, but there is also silent aspiration in which saliva flows during sleep. In addition, aspiration is often seen in elderly people and caregivers who have weakened swallowing power, but it may also occur in young people because it occurs when the throat muscles are relaxed due to excessive alcohol consumption.

Among the pathogens that cause these mycoses, Candida is known to be a major opportunistic infectious bacterium, and it is known that Candida causes mycoses in the oral cavity, mucous membranes, etc. due to immunosuppression on the host side. In addition, it is known that Candida in the oral cavity migrates to the respiratory tract through aspiration or the like, causing pulmonary mycosis and aspiration pneumonia.

In addition, since the lactoferrin of the present technology has the effect of enhancing the antifungal action and the like by the hypothiocyanite production system (preferably, the LPO reaction system), as shown in [Examples] below, It can also be used to enhance the antifungal action and the like of the production system (preferably the LPO reaction system). The lactoferrin can be more preferably used to enhance the anti-Candida action and the like by the hypothiocyanite production system (preferably the LPO reaction system).

Furthermore, the hypothiocyanite production system (preferably, the LPO reaction system) of the present technology has the effect of enhancing the antifungal action of lactoferrin, etc., as shown in [Examples] below. It can also be used to enhance action. The hypothiocyanite production system (preferably the LPO reaction system) can be preferably used to enhance the anti-Candida action of lactoferrin.

When the composition described above is produced using the lactoferrin and hypothiocyanite production system (preferably, lactoferrin and LPO reaction system) of the present technology, the content of these active ingredients is usually 0.005 to 20% by mass, preferably 0.005 to 12.5% by mass. In addition, the above upper limit and lower limit can be arbitrarily combined as desired.

The amount of the above-mentioned composition used by a user per time can be appropriately determined according to the sex, age, condition, etc. of the user.
The amount of the composition described above is used at the same time so that the concentration of lactoferrin and the concentration of hypothiocyanite production system components (preferably, each concentration of LPO reaction system components) in the present technology are achieved. or can be used separately. Moreover, it is more preferable to further adjust the amount of the composition described above so as to achieve the concentration of thiocyanic acid or a salt thereof described above.

The composition described above may be in the form of an aqueous solution composition or in the form of a solid composition.

The combined use of lactoferrin and hypothiocyanite production system components (preferably lactoferrin and LPO reaction system components) of the present technology is preferably carried out in the presence of water. Therefore, in the application area, the composition of the present technology is preferably in a water-containing state.

The present technology uses lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) for the subject or application area to achieve the antifungal action (more preferably anticandida action) described above. It is a method to demonstrate etc. At this time, each of these components may be sequentially added to the subject or application area. Methods of such application include spraying, coating, contacting, and the like.

The present technology exerts an antifungal action within the concentration range of each component described above. Therefore, in the present technology, each concentration of lactoferrin and hypothiocyanite production system (preferably LPO reaction system) when treating a region where fungi exist is preferably within the concentration range described above. Also, the concentration of thiocyanic acid or a salt thereof is preferably within the concentration range described above. Usually, thiocyanic acid is present in the oral cavity, and the lactoferrin and hypothiocyanite production system (preferably, the LPO reaction system) of the present technology acts on the amount of thiocyanic acid present in the oral cavity, resulting in an antifungal effect. can demonstrate

Embodiments of the present technology are not particularly limited, and the following <food and drink>, <compositions applied to the oral cavity>, <medicine>, <external preparation for skin or cosmetic composition>, etc. can be exemplified. However, other implementations are possible.

<Food and drink and feed>
The composition of the present technology can be used as food, drink or feed. For the usage and dosage, the usage and dosage described above can be adopted.
The combination of lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) used in the present technology can be used for human or animal food and drink, health food, functional Effectiveness of food, food for the sick, enteral nutritional food, food for special dietary uses, food with health claims, food for specified health uses, food with function claims, food with nutrient function claims, liquid diet, etc. (hereinafter also referred to as "food and drink, etc.") As a component, it can be used by blending with these.

For example, the combined use of lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology can be , oils and fats, basic seasonings, compound seasonings/foods, frozen foods, confectionery, beverages, other commercially available foods, tablets, liquid diets, feeds (including pets), etc. can be done. Food and drink may be in any form such as liquid, paste, solid, and powder.

The food and drink defined by the present technology can be provided and sold as food and drink with specific uses (especially health uses) and functions indicated.
The food and drink of this technology shall be provided and sold as a food and drink labeled with health applications for use in the above-mentioned antifungal, etc., or for use in the prevention, treatment, and improvement of mycosis caused by aspiration, etc. is possible. Such displays include, for example, displays such as “Those who expect oral care” and “Those who are concerned about oral health”.

The act of "indication" includes all acts to inform consumers of the above-mentioned use. Regardless of the object, medium, etc. to be displayed, all fall under the "display" act of the present invention.

In addition, it is preferable that the "display" be performed in an expression that allows the consumer to directly recognize the use. Specifically, the act of transferring, handing over, displaying for the purpose of transfer or delivery, importing products related to food and beverages or product packaging that describes the above-mentioned use, advertisements related to products, price lists or transaction documents Examples include the act of displaying or distributing information with the above-mentioned use described, or providing information containing such information with the above-mentioned use by electromagnetic means (Internet, etc.).

On the other hand, the content of the display is preferably a display approved by the government (for example, a display that is approved based on various systems established by the government and performed in a manner based on such approval). In addition, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, POP and other advertising materials at sales sites, other documents, and the like.

In addition, "labeling" includes labeling as health food, functional food, enteral nutrition food, food for special dietary use, food with health claims, food for specified health use, food with nutrient function claims, food with function claims, and the like. Among these, in particular, the labeling approved by the Consumer Affairs Agency, for example, the labeling approved by the system related to food for specified health use, food with nutrient function claims, or food with function claims, or similar system. Specifically, labeling as a food for specified health use, labeling as a food for specified health use with certain conditions, labeling to the effect that it affects the structure and function of the body, labeling to reduce the risk of disease, labeling for functionality based on scientific evidence. Labeling, etc. can be mentioned, more specifically, the Cabinet Office Ordinance Concerning Permission for Special Use Labeling as stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009) A typical example is labeling as a food for specified health use (especially labeling for health use) and similar labeling.

Examples of the food and drink include fermented food and drink, but when the fermented food and drink are produced, the lactoferrin and hypothiocyanite production system (preferably, lactoferrin and LPO reaction system) of the present technology are blended. good too. Furthermore, sweeteners such as sucrose, pectin, fruits, fruit juices, agar, gelatin, fats and oils, flavors, coloring agents, stabilizers, reducing agents, and the like may be added. Moreover, you may fill a container with fermented food/beverage products suitably.
The fermented food/beverage product obtained by the method for producing a fermented food/beverage product described above can be appropriately processed in the same manner as a normal fermented food/beverage product.
The fermented food and drink obtained as described above contains the lactoferrin and hypothiocyanite production system (preferably, lactoferrin and LPO reaction system) of the present technology, thereby exhibiting the efficacy of the present technology satisfactorily. can do.

In addition, the present technology can be used as an active ingredient of animal feed for use in antifungals and the like as described above. This technology can be added to a known feed to prepare it, or can be mixed in feed ingredients to produce a new feed.
Raw materials for the feed include, for example, cereals such as corn, wheat, barley, and rye; brans such as wheat bran, wheat bran, rice bran, and defatted rice bran; animal feeds such as fish meal and bone meal; yeasts such as brewer's yeast; mineral feeds such as calcium phosphate and calcium carbonate; oils and fats; Examples of the form of the feed include pet feed (pet food, etc.), livestock feed, fish feed, and the like.

<Composition to be applied in the oral cavity>
The lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology can be used as a composition to be applied in the oral cavity. This is effective for prevention, amelioration or treatment of mycoses such as candidiasis. In addition, it is desirable to apply directly to affected areas (oral cavity, pharynx, etc.) where symptoms are likely to occur.
In addition, as the usage and dosage of the present technology, the usage and dosage described above can be adopted.

The composition to be applied in the oral cavity of the present technology is not particularly limited. Various products for the oral cavity such as cosmetics to be applied to the oral cavity, sanitary products to be applied to the oral cavity, and deodorant products to be applied to the oral cavity can be exemplified.
Specific usage forms of these are not limited to the following, but include, for example, toothpastes, thickening agents, lozenges, mouthwashes, mouthsprays, gels, films, denture cleansers, oral disinfectants, and the like. be done.
In addition, as products in the nursing care category, for example, thickeners, wet wipes, additives for enhancing the effects of oral care products (mouth sponges, brushes, swabs, tongue brushes, mouthpieces, swallowing training products, tongue training products, etc.) etc. can also be exemplified.

The subject of administration of the composition to be applied in the oral cavity of the present technology is usually preferably a human, but mammals other than humans, such as pet animals such as dogs and cats, livestock such as cattle, sheep, and pigs (preferably) pets) are also possible.

The form of use (or formulation) may be either a solid formulation or a liquid formulation. Examples include tablets, pills, capsules, powders, granules, solutions, injections, powders, spray formulations, and the like. but not limited to these.

The composition to be applied in the oral cavity of the present technology may contain an acceptable carrier in terms of foods, beverages or pharmaceuticals. Such carriers include excipients or diluents such as dextrans, saccharose, lactose, maltose, xylose, trehalose, mannitol, sorbitol, gelatin, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylmethylcellulose, gum arabic, guar gum. , tragacanth, acrylic acid copolymer, ethanol, physiological saline, Ringer's solution and the like.

In addition to the carrier, additives such as preservatives, stabilizers, binders, pH adjusters, buffers, thickeners, gelling agents, antioxidants and the like can be added as necessary. These additives are preferably those used in food and drink or pharmaceuticals.

The composition to be applied to the oral cavity containing the lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology as active ingredients is a conventional method in the technical field of oral compositions or according to it. It can be manufactured according to the method. Moreover, you may use it combining the component used for other oral cavity.

According to the present technology, the composition applied to the oral cavity for use in the above-described antifungal or the like in the oral cavity or for the prevention of mycosis caused by aspiration or the like is combined with other oral agents or antifungal agents may be used as Oral agents and antifungal agents used in combination can be administered at any time, prior to, or after administration of the composition. The dosage is not particularly limited, but in the case of a commercially available oral preparation or antifungal agent, it is preferably the dosage indicated by the manufacturer of the oral care product or antifungal agent.

Thus, the present technology can be used in a wide range of fields such as food and drink, functional foods, feeds, pharmaceuticals, quasi-drugs, cosmetics, sanitary products, oral care products, and deodorant products.

<Pharmaceuticals>
The lactoferrin and hypothiocyanite production system (preferably lactoferrin and LPO reaction system) of the present technology can be used for pharmaceutical applications. As a result, it is effective in preventing, improving or treating mycoses such as ringworm, candidiasis, cryptococcosis, and aspergillosis. In addition, the drug can be applied to superficial mycoses, deep skin mycoses, opportunistic infections, keratomycoses, and the like. In addition, application sites include skin (e.g., hair, nails, skin (epidermis and dermis), genitalia, armpits, etc.) and mucous membranes (e.g., vagina, mucous membranes of eyes, etc.), and directly to affected areas where symptoms are observed. It is preferable to use
In addition, the pharmaceuticals of the present technology include formulations for oral administration, formulations for intraoral administration, formulations for administration by injection, formulations for dialysis, formulations for bronchi and lungs, formulations for eye administration, and formulations for ear administration. , nasal formulations, rectal formulations, vaginal formulations, or topical formulations.
In addition, the “medicine” referred to here includes aspects of pharmaceuticals and quasi-drugs in the present technology. In addition, the usage and dosage of this technology in medical use can adopt the usage and dosage described above.

Examples of administration routes include oral administration, transmucosal administration, intranasal administration, and intrarectal administration. Among these, oral administration (oral intake) is preferred.
The subject of administration is usually preferably a human, but mammals other than humans, such as pet animals such as dogs and cats, and domestic animals such as cattle, sheep and pigs, are also included.

The dosage form (or formulation) may be either a solid formulation or a liquid formulation, and examples thereof include tablets, pills, capsules, powders, granules, solutions, injections, powders, spray formulations, and the like. be done.

A medicament of the present technology may contain a pharmaceutically acceptable carrier. Such carriers include excipients or diluents such as dextrans, saccharose, lactose, maltose, xylose, trehalose, mannitol, sorbitol, gelatin, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylmethylcellulose, gum arabic, guar gum. , tragacanth, acrylic acid copolymer, ethanol, physiological saline, Ringer's solution and the like.

In addition to the carrier, additives such as preservatives, stabilizers, binders, pH adjusters, buffers, thickeners, gelling agents, antioxidants and the like can be added as necessary. These additives are preferably those used in pharmaceuticals.

When producing a medicament containing the lactoferrin and hypothiocyanate production system (preferably lactoferrin and LPO composition) of the present technology as active ingredients, a method commonly used in the field of formulation technology, for example, as described in the Japanese Pharmacopoeia It can be produced according to the method or a method based thereon.

The above-described antifungal drug or the drug for preventing mycosis caused by aspiration or the like according to the present technology may be used in combination with other drugs. Pharmaceutical agents used in combination can be administered at any time, prior to, or following administration of the compositions of the present technology. The dosage is not particularly limited, but in the case of commercially available pharmaceuticals, it is preferably the dosage indicated by the pharmaceutical manufacturer.

<External preparation for skin or cosmetic composition>
The external skin preparation or cosmetic composition of the present technology can be blended with other ingredients that are blended in ordinary external skin preparations or cosmetic compositions within a range that does not impair the effects of the present technology. The external skin preparation or cosmetic composition of the present technology can be produced according to a method commonly used in the art.

Other components include, for example, solid oils, vegetable fats, silicone compounds, monohydric lower alcohols, polyhydric alcohols, higher alcohols, higher fatty acids, organic powders, inorganic powders, water-soluble polymers, film-forming agents, interfaces Contains activators, thickeners, gelling agents, UV absorbers, UV shielding agents, preservatives, antibacterial agents, anti-inflammatory agents, fragrances, antioxidants, pH adjusters, chelating agents, vitamins, plant extracts, etc. can do.

As the form of the external skin preparation or cosmetic composition of the present technology, within the range that does not impair the effect of the present technology, for example, deodorants, lotions, milky lotions, creams, eye creams, beauty essences, massage agents, pack agents, hands It can be used as skin cosmetics such as creams, body creams, cleansers, scalp care agents, and quasi-drugs.

The external skin preparation or cosmetic composition is preferably applied to the skin where mycosis is likely to occur (eg, head, armpit, skin, nails, hair, pubic area, etc.). This makes it possible to prevent, ameliorate or treat mycoses. Examples of such mycoses include ringworm and candidiasis.
The method of application is not limited, but a method of applying the composition of the present technology directly to the skin with hands or fingers; a method of impregnating a nonwoven fabric or the like with the composition and applying it; Examples include a method of applying the composition by discharging it onto the skin; a method of spraying the composition onto the skin, and the like.

Thus, the present technology can be used in a wide range of fields.

Moreover, this technique can also employ|adopt the following structures.
[1] A method for preventing, treating, or improving mycoses, or symptoms or diseases caused by fungi, using lactoferrin and a hypothiocyanite-producing system as active ingredients in the presence of thiocyanic acid or a salt thereof.
[2] Use of lactoferrin and a hypothiocyanite production system for the production of an antifungal composition.
[3] A lactoferrin and hypothiocyanite production system for antifungal use or for the prevention, treatment or improvement of mycosis.
[4] Use of lactoferrin and a hypothiocyanite production system for antifungal purposes.
[5] An antifungal composition containing lactoferrin, lactoperoxidase, glucose oxidase and glucose as active ingredients and used in the presence of thiocyanic acid or a salt thereof.
[6] A method for preventing, treating, or ameliorating mycoses, or symptoms or diseases caused by fungi, using lactoferrin, lactoperoxidase, glucose oxidase, and glucose as active ingredients in the presence of thiocyanic acid or a salt thereof.
[7] Use of lactoferrin, lactoperoxidase, glucose oxidase and glucose for the production of an antifungal composition.
[8] Lactoferrin, lactoperoxidase, glucose oxidase and glucose, or uses thereof for antifungal purposes.
[9] An antifungal agent kit using a lactoferrin and LPO reaction system, comprising at least an agent containing lactoferrin and an agent containing lactoperoxidase.
[10] A composition containing lactoferrin as an active ingredient and enhancing the antifungal action of the LPO reaction system.
[11] A composition containing lactoperoxidase, glucose oxidase and glucose as active ingredients and enhancing the antifungal action of lactoferrin.

[12] The composition according to any one of [5] to [11], which is a food or drink, a feed, or an oral composition.
[13] The composition according to any one of [5] to [11], which is a pharmaceutical, cosmetic composition or external preparation for skin.
[14] The composition of any one of [5] to [13], wherein the fungus is Candida.
[15] The composition according to any one of [5] to [14], wherein the mass ratio of lactoperoxidase to lactoferrin is 1:1000 to 10:1.
[16] The composition according to any one of [5] to [15], wherein the mass ratio of lactoperoxidase and glucose oxidase used is 1:1000 to 10:1.
[17] The composition according to any one of [5] to [16], wherein the mass ratio of glucose oxidase to glucose used is 1:100 to 1:1.
[18] The composition according to any one of [5] to [17], wherein the mass ratio of lactoperoxidase, glucose oxidase and glucose used is 1:5-10:9-16.

The present technology will be described in more detail below using test examples, examples, comparative examples, and the like, but the present technology is not limited to these test examples, examples, and the like.

[Test Example 1]
(1) Preparation of sample Bovine lactoferrin (manufactured by Morinaga Milk Industry Co., Ltd.) was dissolved in purified water to prepare a 5% by mass lactoferrin solution (undiluted solution).
Lactoperoxidase (manufactured by DOMO), glucose oxidase (manufactured by Shinnihon Chemical Industry Co., Ltd.) and glucose (manufactured by Nacalai Tesque) are raw materials, and the mass ratio is lactoperoxidase: glucose oxidase: glucose = 1:9:10. Each raw material was mixed as described above to prepare an LPO reaction system component (undiluted solution).
A 40 mM phosphate buffer (pH 7.7) containing 0.66 mM sodium thiocyanate was used.

〔Method〕
C. to each well of a 96-well flat bottom plate. After adding 100 μL of the albicans bacterial solution, LF solutions of various concentrations, LPO reaction system components of various concentrations, and a total of 100 μL of thiocyanic acid solution were added and incubated in a CO ₂ incubator at 37° C. for 16 hours. After that, AlamarBlue staining solution, which is a redox reagent, was dispensed into each well and further incubated for 26 hours, and the metabolic capacity was quantified by absorbance (570 nm/594 nm).
As shown in Table 1, LF undiluted solution was added to each well at final concentrations of 0, 125, 500 and 2000 μg/1 mL, and LPO reaction system component undiluted solution was added at final concentrations of 0, 125 and 500 μg/1 mL. , and 12 samples were set. In addition, as low concentration conditions, as shown in Table 2, the LF undiluted solution was adjusted to final concentrations of 0, 7.5, 31.25, and 125 μg/1 mL, and the LPO reaction system component undiluted solution was adjusted to final concentrations of 0, 31. 25, 125 μg/1 mL, and 12 additional samples were set. At these times, sodium thiocyanate in each well was 0.6 mM.

〔result〕
Neither LF alone nor the LPO reaction system components alone exhibited Candida metabolism inhibitory effects, while the combined use of LF and LPO reaction system components almost completely inhibited Candida metabolism even at low concentrations (Table 1, Table 1). Table 2).

After the 16-hour incubation of the above 12 samples, C. When the morphology of albicans was observed, changes such as shortening of the hyphae were observed with LF alone and with the LPO reaction system components alone as compared to the non-addition condition, but the changes were limited (Fig. 1). On the other hand, it was observed that the combined product of LF and LPO reaction system components clearly changed its morphology and had fewer hyphae. Although not shown in the results of the metabolic capacity suppression effect in FIG. , it was also confirmed that the mycelium decreased.

As described above, although each of the LF and LPO reaction system components alone did not exhibit an antifungal effect, the combined use of the LF and LPO reaction system components exhibited a dramatic antifungal effect. Considering that each of the LF and LPO reaction system components alone could hardly exert antifungal action, it can be said that the antifungal action of the combined ingredients, lactoferrin, lactoperoxidase, glucose oxidase and glucose, is already a different effect. I get it.

Specifically, a mixture of LF and LPO reaction system components (LPO reaction system components: 31.25 µg/mL and LF: 31.25 µg/mL) was used to prepare LPO reaction system components alone (LPO reaction system components: 500 µg/mL). and about 15 times or more than that of LF alone (LF: 2000 μg/mL), and in this case, the rate of inhibition of fungal metabolic capacity was enhanced to almost 100%.

From the above, the combined use of lactoferrin and the LPO reaction system component has extremely excellent fungal metabolism inhibitory action and antifungal action. That is, the combined use of lactoferrin and a hypothiocyanite-producing system has extremely excellent fungal metabolism inhibitory action and antifungal action.

Furthermore, the combined use of lactoferrin and LPO reaction system components can significantly reduce fungal metabolic capacity even at low doses. In addition, since it can be used in a low dose, it is also possible to reduce the amount of each of the lactoferrin and LPO reaction system components used. Furthermore, since both lactoferrin and the LPO reaction system component have been eaten for a long time, they are highly safe and can be used for a long period of time. In addition, it is considered that the combined use of lactoferrin and LPO reaction system components is less likely to cause drug resistance in fungi.

<Prescription example>
An example of prescription of the present technology is given below, but the present technology is not limited thereto.

[Prescription example 1 (for food and drink)]
An antifungal food or drink is produced by blending the LF and the LPO reaction system component in the gummy food or drink so that the LPO reaction system component is 31.25 μg/g and the LF is 31.25 μg/g, respectively.
Antifungal gummy can be expected to have an antifungal action (anticandida action).

[Prescription example 2 (for oral care)]
A mixture of LF and LPO reactive components is formulated in an oral spray at 31.25 μg/mL LPO reactive components and 31.25 μg/mL LF, respectively, to produce an antifungal spray solution.
Antifungal spray liquids can be expected to have antifungal action (anticandida action) in the oral cavity and pharynx.

[Prescription example 3 (for oral care)]
A mixture of LF and LPO reaction system components was blended in a thickening agent containing a thickener so that the LPO reaction system component was 31.25 μg/mL and LF was 31.25 μg/mL, respectively, to provide an oral care antibacterial agent. Manufacture thickening agents for fungi.
By orally ingesting an antifungal thickening agent, or by applying it to the subject's lips, oral cavity, or oral tube, an antifungal action (anticandida action) in the oral cavity can be expected, especially the lung Prevention of mycoses and aspiration pneumonia can be expected.

[Prescription Example 4 (medicine use)]
As an example of a medicine, a mixture of LF and LPO reaction system components is blended in an antifungal agent so that the LPO reaction system component is 31.25 μg / g and LF is 31.25 μg / g, respectively, and the antifungal agent ( For example, eye drops, ointments, tablets) are manufactured.
In addition, as an example of a medicine, lactoferrin and a hypothiocyanite-producing system are blended into an antifungal drug to produce an antifungal drug (eg, eye drops, ointment, tablet).
Antifungal agents can be expected to have antifungal action (anticandida action).

[Prescription Example 5 (for external use on the skin)]
As an example of an external preparation for skin, a mixture of LF and LPO reaction system components is blended in a skin spray liquid so that the LPO reaction system component is 31.25 μg/mL and LF is 31.25 μg/mL, respectively. Manufacture an antifungal spray solution to be sprayed on
As an example of an external preparation for skin, lactoferrin and a hypothiocyanite-producing system are blended in a skin spray liquid to produce an antifungal spray liquid to be sprayed onto the skin.
By spraying the antifungal spray liquid onto the skin (armpits, pubic area, scalp, etc.), antifungal action (anticandida action) can be expected against fungi existing on the skin.

[Prescription Example 6 (medicine use)]
As an example of a medicine, a mixture of LF and LPO reaction system components was added to emulsion so that the LPO reaction system component was 31.25 μg/mL and the LF was 31.25 μg/mL, respectively, to impart an antifungal effect. manufacture emulsion.
As an example of a pharmaceutical, an antifungal action-imparted emulsion is produced by blending lactoferrin and a hypothiocyanite-producing system in an emulsion.
By applying an antifungal action-imparted milky lotion to the skin, antifungal action (anticandida action) on the skin can be expected, and prevention of mycoses that cause skin troubles can be expected.

Claims (6)

containing lactoferrin and LPO reaction system as active ingredients, used in the presence of thiocyanic acid or a salt thereof,
The anti- Candida composition , wherein the lactoferrin is applied at a concentration of 2 μg/mL to 2000 μg/mL . Contains lactoferrin, lactoperoxidase, glucose oxidase and glucose as active ingredients and is used in the presence of thiocyanic acid or a salt thereof ,
The anti- Candida composition , wherein the lactoferrin is applied at a concentration of 2 μg/mL to 2000 μg/mL . The composition is a drug, quasi-drug, cosmetic, or sanitary product (excluding quasi-drugs applied to the oral cavity, cosmetics applied to the oral cavity, and sanitary products applied to the oral cavity) 3. The composition of claim 1 or 2, wherein the composition is The drug is an oral formulation, a formulation for intraoral administration, a formulation for administration by injection, a formulation for dialysis, a formulation for bronchi/lungs, a formulation for administration to the eye, a formulation for administration to the ear, and a formulation for administration to the nose. 4. The composition of claim 3, which is an oral formulation, a rectal formulation, a vaginal formulation, or a topical formulation. 3. The composition according to claim 1 or 2 , wherein the composition is food, drink or feed, or a composition to be applied in the oral cavity (excluding pharmaceuticals to be applied in the oral cavity). 6. The composition according to claim 5, wherein the composition for intraoral application is a quasi-drug for intraoral application, a cosmetic product for intraoral application, or a sanitary product for intraoral application.

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