External preparation

Abstract

To provide an external preparation which has a low risk of side effects and is effective for relieving pain, allergic rhinitis, eye fatigue or obesity.SOLUTION: An external preparation containing nanodiamond as an active ingredient, which is used for alleviating pain, allergic rhinitis, eye fatigue, or obesity.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an external preparation, and in particular to an external preparation containing nanodiamonds as an active ingredient. [Background technology]

[0002] Conventionally, various pharmaceuticals and medical devices have been used to treat and alleviate symptoms such as pain, including lower back pain and stiff shoulders, and allergies. In particular, topical preparations containing active ingredients such as anti-inflammatory analgesics and anti-inflammatory agents, which are absorbed through the skin to treat and alleviate symptoms, have been widely used. However, topical preparations containing anti-inflammatory analgesics and anti-inflammatory agents have had issues, such as the risk of side effects from the active ingredients.

[0003] In recent years, advances in nanotechnology have attracted attention for the application of nanomaterials to medicine. In particular, nanodiamonds are novel carbon materials that, in addition to their high surface area, chemical stability, and biocompatibility, are highly versatile, capable of binding and delivering a variety of drugs, imaging reagents, proteins, and the like (see, for example, Non-Patent Documents 1 and 2). For this reason, nanodiamonds are expected to have new applications in the medical field, such as drug delivery, biomaterial reinforcement, and diagnostic imaging. Technologies related to the production of nanodiamonds have been reported, for example, in Patent Documents 1 and 2. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-001983 [Patent Document 2] Japanese Patent Application Laid-Open No. 2010-126669 [Non-patent literature]

[0005] [Non-Patent Document 1] J Li, et al. Nanodiamonds as intracellular transporters of chemotherapeutic drug. Biomaterials. 2010 Nov;31(32):8410-8. [Non-patent document 2] G Xi, et al. Convection-enhanced delivery of nanodiamond drug delivery platforms for intracranial tumor treatment. Nanomedicine. 2014 Feb;10(2):381-91. Summary of the Invention [Problem to be solved by the invention]

[0006] As a result of extensive research into topical preparations containing nanodiamonds, the present inventors have discovered for the first time that they are effective in relieving various symptoms such as pain, allergic rhinitis, eye fatigue, obesity, etc. As shown in Non-Patent Documents 1 and 2, etc., studies have been reported that attempt to apply nanodiamonds to the medical field, but no research has yet been reported that has investigated the alleviating effects of including nanodiamonds themselves in topical preparations as an active ingredient for relieving pain, allergic rhinitis, eye fatigue, obesity, etc.

[0007] An object of the present invention is to provide an external preparation that has a low risk of side effects and is effective in alleviating pain, allergic rhinitis, eye fatigue, or symptoms of obesity. [Means for solving the problem]

[0008] As a result of intensive research conducted by the inventors to solve the above problems, they discovered that a specific topical agent containing nanodiamonds could solve the above problems, and thus completed the present invention. That is, the present invention is as follows. (1) An external preparation containing nanodiamonds as an active ingredient, which is used to relieve pain, allergic rhinitis, eye fatigue, or obesity. (2) The topical agent according to (1), wherein the nanodiamond is a surface-modified nanodiamond having a functional group containing at least one heteroatom on the surface of the primary particle. (3) The topical preparation according to (2), wherein the heteroatom is selected from the group consisting of a hydroxy group, a hydroxyalkyl group, and a carboxy group. (4) The external preparation according to any one of (1) to (3), wherein the pain is at least one selected from the group consisting of headache, shoulder pain associated with stiff shoulders, lower back pain, and joint pain. (5) An external preparation according to any one of (1) to (4), which is an ointment containing petrolatum or olive oil as a main ingredient. (6) The content of the nanodiamond is 0.05% by mass to 5% by mass; The topical agent according to (5), wherein the total amount of the nanodiamond and the petrolatum or olive oil is 98% by mass or more. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide an external preparation that has a low risk of side effects and is effective in alleviating pain, allergic rhinitis, eye fatigue, or obesity. DETAILED DESCRIPTION OF THE INVENTION

[0010] The topical agent of the present invention will be described in detail below, but the explanation of the constituent elements described below is an example (representative example) of one embodiment of the present invention, and the present invention is not limited to these contents.

[0011] (topical agent) The topical preparation of the present invention contains nanodiamonds as an active ingredient. Nanodiamonds are known to be highly chemically stable and have excellent biocompatibility. Therefore, the risk of side effects is significantly lower in the topical preparation of the present invention compared to conventional topical preparations.

[0012] <Nanodiamond> The nanodiamonds used in the present invention are typically nanodiamond particles (powder). Nanodiamonds can be obtained by, for example, detonation, high-temperature, high-pressure, or laser treatment. Conventional laser treatment methods can be used, but they may also include, for example, a process of preparing carbon soot from pure graphite, a process of forming a multi-component target from the carbon soot and hydrocarbons (wax), a process of laser treatment of the target in liquid, and a process of separating the nanodiamonds by oxidation, flotation, washing, and drying. Nanodiamonds obtained by detonation are preferred due to their superior dispersibility. Known detonation methods include air-cooled detonation and water-cooled detonation, and either method may be used. Nanodiamonds obtained by detonation often contain metal oxides, graphite, etc. The nanodiamonds used in the present invention may be those from which metal oxides and graphite have been removed by acid treatment or oxidation treatment. Acid treatment can be performed, for example, by treating the nanodiamonds in an aqueous solvent using a strong acid such as hydrochloric acid, hydrofluoric acid, sulfuric acid, nitric acid, or aqua regia. The oxidation treatment can be carried out by a method using an oxidizing agent such as chromic acid, chromic anhydride, dichromic acid, or permanganic acid.

[0013] Nanodiamonds, like bulk diamonds, have sp atoms of carbon atoms. 3The structure is the basic skeleton. Generally, a wide variety of functional groups are present on the surface of nanodiamond particles. Examples of such functional groups include alkyl groups, carboxyl groups, hydroxyl groups, ketone groups, vinyl groups, and lactone groups. Nanodiamonds with selectively enhanced functional group modification rates and nanodiamonds surface-modified with compounds or functional groups are also commercially available. Depending on the type of compound or functional group, surface-modified nanodiamonds can achieve, for example, improved affinity with organic materials and even higher thermal conductivity. The nanodiamonds used in the present invention may be nanodiamonds that are not surface-modified with compounds or functional groups, or they may be surface-modified with compounds or functional groups.

[0014] Surface-modified nanodiamonds are not particularly limited, but preferably have at least one heteroatom-containing functional group on the surface of the nanodiamond. The presence of at least one heteroatom-containing functional group on the surface of the nanodiamond tends to suppress aggregation of nanodiamond particles in topical preparations. Examples of heteroatom-containing functional groups include hydroxyl groups (-OH), hydroxyalkyl groups (-CH2OH, -ROH: R indicates an alkyl group), carboxyl groups (-COOH), amino groups (-NH2), alkylamino groups (-NHR, -NR2: R indicates an alkyl group), and thiol groups (-SH). Among these, hydroxyl groups, hydroxyalkyl groups, and carboxyl groups are preferred as heteroatom-containing functional groups. Only one type of nanodiamond may be used, or two or more types may be used.

[0015] The nanodiamonds used in the present invention may be commercially available nanodiamonds as they are. Examples of commercially available nanodiamonds having hydroxyl groups or hydroxyalkyl groups on the surface of the nanodiamond (hereinafter also referred to as surface hydroxylated nanodiamonds) include, for example, the product name "RT-DND-L" (manufactured by Ray Techniques). Examples of nanodiamonds having carboxyl groups on the surface (hereinafter also referred to as surface carboxylated nanodiamonds) include, for example, the product name "RT-DND-C" (manufactured by Ray Techniques).

[0016] Nanodiamonds generally refer to diamonds with an average particle size (particle size D50) of less than 1 μm. The average particle size of the primary particles of the nanodiamonds used in the present invention is not particularly limited, but is preferably 1 nm or more, more preferably 2 nm or more, and even more preferably 3 nm or more. The average particle size is preferably 50 nm or less, more preferably 30 nm or less, and even more preferably 10 nm or less. If the average particle size of the nanodiamonds is within the above range, they tend to have excellent dispersibility in the base and excellent relaxation effects. The average particle size of the primary particles can be measured, for example, by small-angle X-ray scattering (SAXS).

[0017] In the case of topical preparations in which nanodiamonds are dispersed in water or organic solvents, the nanodiamonds are active in both aggregate (cluster) and highly dispersed states. In other words, the topical preparation of the present invention exerts a mitigating effect as long as the average particle size of the primary particles is within the above range, regardless of the dispersion state of the nanodiamonds.

[0018] The content of nanodiamond in the external preparation is not particularly limited, but from the viewpoint of obtaining sufficient relaxation effect, it is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and even more preferably 0.1% by mass or more.In addition, from the viewpoint of cost-effectiveness, the content is preferably 10% by mass or less, more preferably 5% by mass or less, and even more preferably 1% by mass or less.

[0019] (Dosage form) The topical preparation of the present invention is only required to contain nanodiamonds, and the dosage form is not particularly limited.The dosage form of the topical preparation can be, for example, an ointment, a cream, a patch, a lotion, a gel, a foam, etc.Among these, the topical preparation of the present invention is preferably an ointment or a cream, more preferably an ointment, because it tends to have a stronger soothing effect.

[0020] <Ointment> Constituents of ointments include, for example, bases, moisturizers, thickeners, etc. Bases include higher hydrocarbons, oils and fats, waxes, fatty acids, higher alcohols, esters, etc. Higher hydrocarbons include, for example, squalane, synthetic paraffin, liquid paraffin, plasmodium liquid paraffin, petrolatum, microcrystalline wax, etc. Oils and fats include, for example, olive oil, jojoba oil, sesame oil, soybean oil, cacao oil, camellia oil, peanut oil, beef tallow, lard, chicken oil, triacetin, hydrogenated castor oil, etc. Waxes include, for example, beeswax, white beeswax, lanolin, ceresin, etc. Fatty acids include, for example, stearic acid, oleic acid, etc. Higher alcohols include, for example, lanolin alcohol, cetostearyl alcohol, etc. Esters include, for example, isopropyl myristate, stearyl myristate, medium-chain fatty acid triglycerides, etc.

[0021] Examples of moisturizing agents include glycerin and 1,3-butylene glycol. Examples of thickeners include carboxyvinyl polymers and carboxymethyl cellulose.

[0022] The ointment of the present invention preferably contains petrolatum or olive oil as its main ingredient. Petrolatum is preferred because it forms a film on the skin when applied, preventing moisture evaporation and the penetration of allergens. It is also preferred because it allows nanodiamonds to remain on the skin for a long time, providing a continuous effect. As the petrolatum, it is preferable to use white petrolatum equivalent to that for medical use.

[0023] The ointment of the present invention, even when containing olive oil as a main component, exhibits effects equal to or greater than those of the above-mentioned petrolatum. Olive oil may be either unrefined or refined. Examples of unrefined olive oil include extra virgin olive oil (the name given by the International Olive Oil Council (IOC), hereinafter the same), virgin olive oil, and ordinary virgin olive oil. These olive oils may be used alone or in combination of two or more types. Olive fruits used as the raw material for olive oil may be domestically produced or may be imported from Italy, Greece, or other countries.

[0024] The ointment of the present invention is preferably an ointment essentially consisting of nanodiamonds and petrolatum or olive oil. Nanodiamonds, petrolatum, and olive oil all have few side effects, and ointments consisting of these ingredients are suitable for long-term use. Therefore, the ointment of the present invention preferably contains nanodiamonds and petrolatum or olive oil in a total amount of 98% by mass or more, and can be 99% by mass or more, 99.5% by mass or more, 99.8% by mass or more, or 99.9% by mass or more, and can be 100% by mass, excluding other ingredients. Other ingredients include unavoidable impurities that are present during manufacturing.

[0025] <Cream> Constituents of creams include oil-soluble substances, water-soluble substances, moisturizers, emulsifiers, etc. Examples of oil-soluble substances that can be used include higher hydrocarbons, oils and fats, waxes, fatty acids, higher alcohols, esters, etc. Examples of higher hydrocarbons include squalane, synthetic paraffin, liquid paraffin, plasma liquid paraffin, petrolatum, and microcrystalline wax. Examples of oils and fats include olive oil, jojoba oil, sesame oil, soybean oil, cacao oil, camellia oil, peanut oil, beef fat, lard, chicken fat, triacetin, and hydrogenated castor oil. Examples of waxes include beeswax, white beeswax, lanolin, and ceresin. Examples of fatty acids include stearic acid and oleic acid. Examples of higher alcohols include lanolin alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, and cholesterol. Examples of esters include isopropyl myristate, stearyl myristate, and medium-chain fatty acid triglycerides.

[0026] Examples of water-soluble substances that can be used include water, solvents, thickeners, pH adjusters, preservatives, etc. Examples of solvents include lower alcohols such as ethanol, propanol, and isopropanol. Examples of thickeners include carboxyvinyl polymers and carboxymethylcellulose. Examples of pH adjusters include diisopropanolamine, triisopropanolamine, triethanolamine, L-arginine, potassium hydroxide, sodium hydroxide, sodium lactate, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, lactic acid, citric acid, and glacial acetic acid. Examples of preservatives include thymol, dibutylhydroxytoluene, sodium edetate hydrate, phenoxyethanol, sodium benzoate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, and propyl parahydroxybenzoate.

[0027] Examples of moisturizing agents include petrolatum, glycerin, propylene glycol, and 1,3-butylene glycol, and examples of emulsifying agents include cationic surfactants, anionic surfactants, amphoteric surfactants, and nonionic surfactants.

[0028] <Gel> Constituents of the gel may include, for example, a base, a thickener, a pH adjuster, a preservative, etc. Examples of bases include water, isopropanol, propylene glycol, etc. Examples of thickeners include carboxyvinyl polymer, carboxymethylcellulose, etc. Examples of pH adjusters include diisopropanolamine, triisopropanolamine, triethanolamine, L-arginine, potassium hydroxide, sodium hydroxide, sodium lactate, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, lactic acid, citric acid, glacial acetic acid, etc. Examples of preservatives include thymol, dibutylhydroxytoluene, sodium edetate hydrate, phenoxyethanol, sodium benzoate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, etc.

[0029] <Lotion> Examples of components of lotions include oil-soluble substances, water-soluble substances, moisturizers, emulsifiers, etc. Examples of oil-soluble substances that can be used include higher hydrocarbons, oils and fats, waxes, fatty acids, higher alcohols, esters, etc. Examples of higher hydrocarbons include squalane, synthetic paraffin, liquid paraffin, plasma liquid paraffin, petrolatum, white petrolatum, yellow petrolatum, and microcrystalline wax. Examples of oils and fats include olive oil, jojoba oil, sesame oil, soybean oil, cacao oil, camellia oil, peanut oil, beef fat, lard, chicken fat, triacetin, and hydrogenated castor oil. Examples of waxes include beeswax, white beeswax, lanolin, reduced lanolin, and ceresin. Examples of fatty acids include stearic acid and oleic acid. Examples of higher alcohols include lanolin alcohol, cetyl alcohol, and cetostearyl alcohol. Examples of esters include isopropyl myristate and stearyl myristate.

[0030] Examples of water-soluble substances that can be used include water, thickeners, pH adjusters, preservatives, etc. Examples of thickeners include carboxyvinyl polymers and carboxymethyl cellulose. Examples of pH adjusters include diisopropanolamine, triisopropanolamine, triethanolamine, L-arginine, potassium hydroxide, sodium hydroxide, sodium lactate, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, lactic acid, citric acid, and glacial acetic acid. Examples of preservatives include thymol, dibutylhydroxytoluene, sodium edetate hydrate, phenoxyethanol, sodium benzoate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, and propyl parahydroxybenzoate.

[0031] Examples of moisturizing agents include petrolatum, white petrolatum, yellow petrolatum, glycerin, and 1,3-butylene glycol, and examples of emulsifying agents include cationic surfactants, anionic surfactants, amphoteric surfactants, and nonionic surfactants.

[0032] <Foam> Constituents of foam agents include, for example, bases, foaming agents, pH adjusters, preservatives, etc. Examples of bases include water, glycerin, 1,3-butylene glycol, dipropylene glycol, propylene glycol, D-sorbitol, polyethylene glycol, isopropyl myristate, octyldodecanol, octyldodecyl myristate, hexyldecanol, castor oil, olive oil, medium-chain fatty acid triglycerides, oleyl alcohol, oleic acid, cetyl 2-ethylhexanoate, isostearyl palmitate, cetyl 2-ethylhexanoate, squalane, light liquid paraffin, liquid paraffin, squalene, petrolatum, gelling hydrocarbons, etc. Examples of foaming agents include, for example, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, Examples of pH adjusters include diisopropanolamine, triisopropanolamine, triethanolamine, L-arginine, potassium hydroxide, sodium hydroxide, sodium lactate, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, lactic acid, citric acid, glacial acetic acid potassium dihydrogen phosphate, and sodium edetate. Examples of preservatives include thymol, dibutylhydroxytoluene, sodium edetate hydrate, phenoxyethanol, sodium benzoate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, and propyl parahydroxybenzoate.

[0033] <Patch> Constituent components of the patch include, for example, thickeners, moisturizers, fillers, crosslinking agents, solubilizers, emulsifiers, etc. Specifically, thickeners include, for example, sodium alginate, gelatin, methylcellulose, carboxyvinyl polymer, sodium polyacrylate, etc., moisturizers include, for example, glycerin, etc., fillers include, for example, kaolin, titanium dioxide, zinc oxide, etc., crosslinkers include, for example, acetaldehyde, dimethyl ketone, aluminum sulfate, etc., solubilizers include, for example, alcohols such as ethanol, isopropanol, etc., and emulsifiers include, for example, anionic surfactants, nonionic surfactants, etc.

[0034] <<Surfactants>> Specific examples of cationic surfactants that can be used in the above-mentioned preparations of the present invention include cetyltrimethylammonium chloride, lauryldimethylbenzylammonium chloride, tetrabutylammonium chloride, and dioctadecyldimethylammonium chloride.

[0035] Examples of anionic surfactants include sodium alkylbenzenesulfonate, sodium dodecyl sulfate, sodium coconut alcohol ethoxy sulfate, sodium α-olefin sulfonate, and emulsified cetostearyl alcohol (a mixture of cetostearyl alcohol and sodium cetostearyl sulfate).

[0036] Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene alkylphenol ethers, polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyl stearate, glycerin fatty acid esters, and diglycerin fatty acid esters.

[0037] Examples of amphoteric surfactants include N-alkyl-N,N-dimethylammonium betaine, imidazoline-type amphoteric surfactants, etc. These surfactants can be used alone or in combination.

[0038] The method for producing the topical agent of the present invention is not particularly limited, and it can be produced by appropriately mixing the constituent components using a conventionally known method that is obvious to those skilled in the art.

[0039] (How to apply) The topical preparation of the present invention can improve various symptoms by applying it to the skin around the affected area once to several times a day. The amount of topical preparation to be applied may be appropriately selected depending on the age, weight, symptoms, etc. For example, in the case of an ointment, a few grams of the preparation may be taken on a finger, cloth, paper, cotton swab, etc., and applied directly to the skin around the affected area.

[0040] (effect) The topical preparation of the present invention contains nanodiamonds as an active ingredient, and can alleviate various symptoms. Major symptoms that can be alleviated include pain, allergic rhinitis, eye fatigue, and obesity. The topical preparation of the present invention can alleviate the above symptoms with an extremely low risk of side effects, and can also contribute to improving quality of life (QOL). The major symptoms are described below.

[0041] <Pain> The topical preparation of the present invention can relieve pain by applying it to the area where pain is occurring. While the reasons for its pain relief are not entirely clear, some subjects reported feeling a warmth at the application site, suggesting that this is due to the blood flow-promoting effect of the topical preparation of the present invention. Nanodiamonds have electrical properties, such as a positive or negative zeta potential. When the topical preparation of the present invention is applied to the skin, it is speculated that the electrical properties of nanodiamonds generate an electric current on the skin surface. The generated electric current dilates blood vessels under the skin around the affected area, promoting blood flow and expelling waste products, including pain-inducing substances, thereby relieving pain and stiffness.

[0042] In addition, the case where a hydroxy group, a hydroxyalkyl group, or a carboxy group is used as the surface-modified nanodiamond will be described. Hydroxy groups (and hydroxyalkyl groups) are found in many biologically active substances, particularly antioxidants. For example, phenols are a type of compound containing a hydroxy group and possess potent antioxidant properties. These antioxidants are known to prevent cell damage caused by oxidative stress and suppress inflammatory responses. However, the hydroxy group itself does not directly suppress inflammation; rather, the overall structure and function of the compound determine its effectiveness. The same is true for compounds containing a carboxyl group; some compounds containing this functional group suppress inflammation. For example, some nonsteroidal anti-inflammatory drugs (NSAIDs) contain a carboxyl group, which suppresses inflammation by inhibiting prostaglandin synthesis. However, this is not due to the direct effect of the carboxyl group on inflammation, but rather to the drug's overall structure and mechanism of action. Thus, hydroxyl and carboxyl groups are fundamental building blocks of a wide variety of compounds, and the ability of a particular compound containing them to suppress inflammation depends on the specific structure and mechanism of action of that compound.

[0043] In order for a hydroxyl group to enhance the efficiency of its antioxidant effect, the compound containing that hydroxyl group must have a structure that enhances its ability to capture free radicals. Compounds containing hydroxyl groups that are effective in enhancing antioxidant effect are known to have the following characteristics: Phenolics: Compounds with a phenolic structure (e.g., flavonoids, tannins, resveratrol, etc.) have hydroxyl groups positioned in a way that makes them more susceptible to reaction with free radicals. This makes these compounds powerful antioxidants, preventing cell damage caused by free radicals. Polyphenols: Compounds with multiple hydroxyl groups (e.g., catechin and curcumin) also enhance antioxidant activity. These compounds have the ability to scavenge multiple free radicals with a single molecule. Vitamin E (tocopherol): Vitamin E is a fat-soluble antioxidant whose active site is the hydroxyl group of alpha-tocopherol. This hydroxyl group protects cells by capturing lipid radicals in cell membranes and preventing lipid oxidation. Vitamin C (ascorbic acid): Vitamin C also contains a hydroxyl group and is a powerful water-soluble antioxidant. Vitamin C not only neutralizes free radicals directly, but also contributes to the regeneration of vitamin E, enhancing its antioxidant activity. These compounds utilize hydroxyl groups to efficiently neutralize free radicals, reducing oxidative stress that causes cell damage and inflammation. To increase the efficiency of antioxidant effects, it is recommended to consume foods and supplements rich in these compounds.

[0044] Free radicals are atoms or molecules with at least one unpaired electron. This unpaired electron makes them highly reactive and allows them to easily react with other compounds, resulting in radical reactions. Free radicals are important because their reactivity can cause damage to cells and tissues. In particular, free radicals can react with biomolecules, such as DNA, proteins, and cell membrane lipids, altering their structure and function. This damage is associated with the development of many health problems, including aging, cancer, cardiovascular disease, and neurodegenerative diseases. However, not all free radicals are harmful. Appropriate amounts of free radicals are important tools used by the immune system to destroy invading pathogens and are also involved in cell signaling processes. Therefore, a balanced production and elimination of free radicals is essential in the body. To maintain this balance, molecules called antioxidants exist in the body, which neutralize free radicals, reducing their reactivity and preventing cell damage. Vitamins C, E, and glutathione are typical antioxidants found in nature.

[0045] It is speculated that nanodiamonds may have the ability to capture and neutralize free radicals due to their surface chemical and physical properties. The surface of nanodiamonds can be modified with functional groups such as hydroxyl and carboxyl groups, which enhance their reactivity with free radicals.

[0046] The free radical scavenging ability of nanodiamonds depends on the high surface area of ​​nanodiamonds and the chemical interactions of these functional groups. Nanodiamonds, due to their small size and high surface area ratio, can have a large number of functional groups, which are thought to react with and capture free radicals. For example, it has been reported that nanodiamonds exhibit antioxidant properties and reduce oxidative stress in cells by scavenging free radicals.

[0047] As explained above, although not everything is clear, one of the reasons why the present invention is effective, particularly when surface-modified nanodiamonds are used, is thought to be that nanodiamonds have the ability to capture the above-mentioned free radicals due to their small size and high surface area ratio.

[0048] As used herein, "pain" refers to any pain occurring in a living body, and the location of the pain and the disease causing the pain are not particularly limited. Examples of pain include pain in the head, neck, shoulders, lower back, back, trunk, arms (elbows, wrists to the fingertips), groin, and feet (knees, ankles to the toes). In particular, the topical preparation of the present invention is effective in alleviating symptoms such as headache, shoulder pain associated with stiff shoulders, lower back pain, and joint pain.

[0049] <Allergic rhinitis> Allergic rhinitis is caused by histamine, which is produced in the body by a causative substance (allergen). Suppressing the symptoms caused by histamine is an effective treatment for allergic rhinitis. Symptoms of allergic rhinitis include discomfort around the nose. Allergic rhinitis can also be caused by the entry and adhesion of fine particles such as pollen, PM2.5, house dust, viruses, and mite corpses into the nasal cavity. In this specification, allergic rhinitis also includes hay fever, a seasonal allergic rhinitis.

[0050] When applied to the area around the nostrils, the topical preparation of the present invention prevents the entry of substances that cause allergic rhinitis. This alleviates and prevents the symptoms of allergic rhinitis. Nanodiamonds are also known to be able to decompose and neutralize bacteria, viruses, odorous substances, and other substances that come into contact with nanodiamond particles through oxidation-reduction reactions due to their electrical properties. Therefore, it is believed that the skin around the affected area where the topical preparation is applied can be kept clean, effectively suppressing the symptoms of allergic rhinitis. The topical preparation of the present invention has an extremely low risk of side effects and can be used cleanly for long periods of time, making it suitable for use by anyone, from young children to the elderly, and offering its benefits to a wide range of people.

[0051] <Eye fatigue> The topical preparation of the present invention can relieve eye fatigue by applying it to the area around the eyes. Although the reasons why eye fatigue can be relieved are not entirely clear, it is speculated that this is due to the aforementioned blood flow promoting effect of nanodiamonds. It is speculated that the promotion of blood flow allows oxygen to be appropriately supplied to muscles such as the ciliary muscles and periocular muscles, improving focusing function and the like, thereby alleviating the symptoms of eye fatigue.

[0052] In this specification, "eye fatigue" refers to eye fatigue induced by external stimuli. Eye fatigue states include uncomfortable eye conditions, such as eye strain, blurred vision, stiff shoulders or lower back, and a heavy feeling in the head. Typical examples of eye fatigue include eye fatigue caused by working with visual display terminals (VDTs). Eye fatigue includes physiological eye fatigue, which is a simple feeling of eye fatigue, and pathological eye fatigue, which is perceived as an unpleasant feeling of fatigue and is not sufficiently relieved by rest. Clinically, pathological eye fatigue is sometimes referred to as eye strain, but eye fatigue is generally used synonymously with eye strain. Therefore, in this specification, eye fatigue is used to include eye strain.

[0053] <Obesity> The topical preparation of the present invention can alleviate obesity by applying it to the soles of the feet, etc. The reasons why it can alleviate obesity are not entirely clear, but some subjects have reported that the application site feels warm, suggesting that this is due to the blood flow-promoting effect of the topical preparation of the present invention. When blood flow is promoted, nutrients and oxygen are efficiently transported to various parts of the body. This allows muscles to function normally and increases metabolism. Increased metabolism makes it easier to burn fat, leading to the improvement of obesity. In addition, waste products and harmful substances are efficiently excreted from the body, normalizing metabolism. Normalizing metabolism inhibits fat accumulation and improves obesity.

[0054] In this specification, "obesity" refers to a disease in which excess fat accumulates in the internal organs or subcutaneously, and can be determined, for example, by calculating the BMI (Body Mass Index), which is a body mass index that indicates the degree of obesity calculated from weight and height.

[0055] <Other benefits> The topical preparation of the present invention is expected to have the effect of alleviating various symptoms other than those mentioned above. For example, applying the topical preparation of the present invention to the soles of the feet tends to alleviate the symptoms of athlete's foot. Furthermore, applying the topical preparation of the present invention to the armpits tends to alleviate the symptoms of axillary malodor. These effects are presumed to be due to the antibacterial action of nanodiamonds. It is also expected to have the effect of alleviating tinnitus, symptoms of rhinitis associated with colds, and chronic fatigue. [Example]

[0056] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples. In the examples, "parts", "%", and the like are based on mass unless otherwise specified.

[0057] [Raw materials] The raw materials used in the examples, reference examples and comparative examples are as follows. (nanodiamonds) <d1>Surface hydroxylated nanodiamond (product name: RT-DND-L (manufactured by Ray Techniques), average particle size: 3.5-6.0 nm) <d2>Surface-carboxylated nanodiamond (product name: RT-DND-C (manufactured by Ray Techniques), average particle size: 3.5-6.0 nm) <d3>Nanodiamond (product name: RT-DND (manufactured by Ray Techniques), average particle size: 3.5 to 6.0 nm, surface unmodified) (Base) Vaseline (product name: Chloratum V (manufactured by Croda Japan)) Olive oil (DSP Gokyo Food & Chemical Co., Ltd.)

[0058] (Preparation of topical preparations) <Topical agent E1> An ointment, external preparation E1, was prepared by mixing 0.1 parts by mass of nanodiamond D1 and 99.9 parts by mass of petrolatum. <Topical agent E2> Topical agent E2 was prepared in the same manner as topical agent E1, except that nanodiamond D1 was changed to D2. <Topical agent E3> Topical agent E3 was prepared in the same manner as topical agent E1, except that nanodiamond D1 was changed to D3. <Topical agent E4> External preparation E4 was prepared in the same manner as external preparation E1, except that 99.9 parts by mass of olive oil was used instead of 99.9 parts by mass of petrolatum. <Topical agent E5> 0.05 parts by mass of nanodiamond D1 and 99.95 parts by mass of petrolatum were mixed to prepare topical agent E5, which is an ointment. <Topical agent E6> One part by mass of nanodiamond D1 and 99 parts by mass of petrolatum were mixed to prepare topical agent E6, which is an ointment. <Topical agent E7> 100 parts by mass of Vaseline was used as is.

[0059] [Examples 1 to 36 and Comparative Example 1] Topical preparations E1 to E7 were applied to the subjects as shown in Table 1. For symptoms corresponding to pain, the preparations were applied at least once per day around the area where pain was occurring. For symptoms corresponding to allergic rhinitis, the preparations were applied at least once per day around the nostrils, inside the nasal cavity, and around the subnasal area. For cases with multiple allergies or when the amount of topical preparation remaining in the nasal cavity had decreased after wiping away nasal mucus, the preparations were applied as appropriate every 2 to 3 hours. For symptoms corresponding to eye fatigue, the preparations were applied at least once per day around the eyes. For symptoms corresponding to obesity, the preparations were applied at least once per day to the soles of the feet. For other symptoms, the preparations were applied at least once per day to the application sites shown in Table 1. The results are shown in Table 1.

[0060] [Table 1]

[0061] As shown in Table 1, in Examples 1 to 36, symptoms such as pain, allergic rhinitis, eye fatigue, and obesity were alleviated while using the topical preparations E1 to E6 of the present invention. Note that the topical preparations E1 to E6 of the present invention used in Examples 1 to 36 do not contain any allergens, and therefore have very few side effects and can be used by people of all ages, from infants to the elderly, providing benefits to many people. On the other hand, in Comparative Example 1, in which topical agent E7 was applied, which did not contain nanodiamonds but was prepared by replacing the amount of nanodiamonds with petrolatum, some pain relief was felt immediately after application, but the effect did not last, and the subject discontinued use.

[0062] As explained above, the topical preparation of the present invention can relieve symptoms such as pain, allergic rhinitis, eye fatigue, and obesity.

Claims

1. An external preparation containing nanodiamonds as an active ingredient, which is used to relieve pain, allergic rhinitis, eye fatigue, or obesity.

2. The topical agent according to claim 1, wherein the nanodiamond is a surface-modified nanodiamond having a functional group containing at least one heteroatom on the surface of the primary particle.

3. The topical agent according to claim 2, wherein the heteroatom is selected from the group consisting of a hydroxy group, a hydroxyalkyl group, and a carboxy group.

4. The external preparation according to any one of claims 1 to 3, wherein the pain is at least one selected from the group consisting of headache, shoulder pain associated with stiff shoulders, lower back pain, and joint pain.

5. 2. The topical preparation according to claim 1, which is an ointment containing petrolatum or olive oil as a main ingredient.

6. The content of the nanodiamond is 0.05% by mass to 5% by mass, The topical agent according to claim 5, wherein the total amount of the nanodiamonds and the petrolatum or olive oil is 98% by mass or more.

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