JP2007332078A - Agent for external use containing ozone-dissolved glycerol solution such as cosmetic, quasi-drug or medicament (pharmaceutical) - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an agent for external use having sufficient safety and efficacy and applicable to intact skin or mucosa. <P>SOLUTION: The agent for external use applicable to intact skin or mucosa contains an ozone-dissolved glycerol solution, wherein the initial level of ozone concentration is at least 85 ppm. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to external preparations such as cosmetics, quasi-drugs, and pharmaceuticals (pharmaceuticals) containing an ozone-dissolved glycerin solution.

  External preparations such as medicines, quasi-drugs, and cosmetics are agents that are widely used for the purpose of preventing, treating, and treating beauty or various diseases. Various active ingredients for external preparations are used depending on the purpose of use. For example, in pharmaceuticals and quasi-drugs, pharmaceutical ingredients and ingredients having a slower action than pharmaceutical ingredients are used, and in cosmetics, moisturizing ingredients, whitening ingredients, wrinkle improving ingredients, stain improving ingredients, etc. are used. Yes.

  Ozone is also known as a component of an external preparation. Ozone is a colorless and transparent substance, and since it returns to oxygen immediately after reacting, its tissue damage is extremely weak, so it is easy to handle as a component of an external preparation and is a highly safe substance. As an agent containing ozone, for example, in Patent Document 1 (Japanese Patent Laid-Open No. 10-139645), as an ozone-enclosed viscous material, bactericidal action against acne, pimples, stains, decoloring action against freckles, anti-inflammatory action after sunburn Or cosmetics having a tissue activating effect on the skin, toothpastes, wound ointments, application pastes, ointments and the like.

Patent Document 2 (Japanese Patent Application Laid-Open No. 2003-55107) describes a water-soluble disinfectant obtained by ozone-oxidizing glycerin. In particular, this document discloses ozone-oxidized glycerin (ozone concentration of about 3 ppm in an aqueous solution of about 1% glycerin). ) Is also suitable for hand-washing.
Patent Document 3 (Japanese Patent Application Laid-Open No. 2005-232094) describes a lotion and a cosmetic solution using an ozone-dissolved glycerin solution and a therapeutic agent for wounds. This document also describes that the bactericidal ability can be exhibited particularly when the ozone concentration is 80 ppm or more, and that the wound healing effect can be obtained when the ozone concentration is 500 ppm or more. This document describes the wound healing effect, in particular, along with specific formulations of ozone ointment and ozone gel.

  In Patent Document 3, a concentrated glycerin solution is irritating to human tissue, so that any one of water, petrolatum, and polyethylene glycol is mixed and stirred, a manufacturing method, It also describes that the storage method and solidified product can solve irritation and the like.

Japanese Patent Laid-Open No. 10-139645 JP 2003-55107 A JP 2005-232094 A Maurizio Podda, Hautarzt (2004; 55: 1120-1124)

  As described above, various external preparations are known, but their safety and effects on intact skin or mucous membrane are not always sufficient. Some types of active ingredients are not suitable as external preparations due to their physical properties, such as solubility and odor, oxidative decomposition by ozone, and the like.

Ozone as a component of an external preparation has the advantage that it is easy to handle because it returns to oxygen after decomposition, but it is known as a specific prescription of an ozone-containing external preparation that exhibits a sufficient expected effect. ,
-Ozone-oxidized glycerin of about 1% glycerin aqueous solution for use in hand washing (Patent Document 2), and ozone ointment and ozone gel for wound healing (Patent Document 3)
Only. Patent Document 1 does not describe any specific prescription of the ozone-containing external preparation.
Moreover, since the concentration of glycerin, which is a solvent, is limited as described above, the effect of a lotion containing ozone has not been studied even though it contains ozone at a certain concentration or higher. Rather, since ozone has an oxidizing power, it is generally feared that it may have an adverse effect on the skin, and ozone is even considered to be difficult to apply to intact skin or mucous membranes. For example, from the results of experiments using mice, ozone may cause damage not only to the lungs but also to the skin. “Especially in large cities, synergistic effects with other environmentally hazardous substances can be considered, so caution is necessary. (Non-patent Document 1).
In addition, the results of experiments using mice also reveal that ozone increases the concentration of cellular oxidative metabolites and stress proteins in the skin stratum corneum, while decreasing the concentration of protective antioxidants. (Non-Patent Document 1). For example, in an environment with an ozone concentration of 1 ppm, it has been reported that after 2 hours, tocopherol and ascorbic acid are each reduced by 80% and glutathione by 45%.
Furthermore, in Non-Patent Document 1, mention is also made of the adverse effects of ozone on humans, saying that “unsaturated fatty acids in the stratum corneum may be oxidized by ozone and the barrier function may be impaired, resulting in dermatitis”. Are listed. In particular, in large cities and densely populated areas where smog is likely to occur, the concentration of ozone reaches 0.1 to 0.8 ppm in the summer, and additional environmental hazards such as hydrocarbons, cigarette smoke, and ultraviolet rays add to the synergy. It is believed that the adverse effects of ozone increase due to the action.
Therefore, as a preventive measure against these, Non-Patent Document 1 describes the possibility of alleviating or avoiding the above-mentioned obstacles by applying an antioxidant such as vitamin E or vitamin C in advance. Yes. On the other hand, this document also describes that ozone cannot penetrate deeper or have systemic effects.
Although ozone is a substance having the above-mentioned advantages, its application as an external preparation is limited because of its adverse effects on the human body and difficulty in use.

  In addition, as described above, although various external preparations are known, those having sufficient safety and effect on intact skin or mucous membrane and having suitable physical properties as active ingredients It does n’t exist yet.

  Accordingly, an object of the present invention is to provide an external preparation that can be applied to intact skin or mucous membranes and has sufficient safety and effects.

In order to solve the above-mentioned problems, the present inventor has made various researches on intact skin or mucous membranes, which are surprisingly applied to an external preparation containing dissolved ozone at a higher concentration than conventional ones. As a result of finding that it has an excellent effect and safety against intact skin or mucous membrane is secured, the present invention has been completed as a result of further research.
That is, the present invention relates to at least the following inventions.
(1) The external preparation containing an ozone-dissolved glycerin solution and used for intact skin or mucous membrane, wherein the initial value of the ozone concentration is at least 85 ppm.
(2) The said external preparation which is cosmetics.
(3) The external preparation further comprising at least one of water, a humectant, a thickener, a preservative, a surfactant, an anti-inflammatory agent, ceramide or a precursor thereof, polyethylene glycol, aroma oil, and ethanol.
(4) The said external preparation whose moisturizer is at least 1 sort (s) of hyaluronic acid Na, acetyl hyaluronic acid Na, and derivatives thereof, a thickener is xanthan gum, and an antiseptic | preservative is phenoxyethanol.
(5) The surfactant is Nauroyl sulfate, the moisturizer is PCA-Na, the anti-inflammatory agent is glycyrrhizic acid 2K, and ceramide or a precursor thereof is ceramide 1, ceramide 3, ceramide 6II, phytosphingosine and The said external preparation which is at least 1 sort (s) of cholesterol and a preservative is phenoxyethanol.
(6) The external preparation further comprising at least one of polyethylene glycol 450 and polyethylene glycol 65M.
(7) The external preparation further comprising ethanol and / or at least one aroma oil.
(8) The external preparation according to any one of claims 3 to 7, further comprising water that is acidic water.
(9) The said external preparation used for 1 or 2 or more of the reduction | decrease of water transpiration | evaporation in a skin or a mucous membrane, reduction of a stain, and improvement of a sagging.
(10) The said external preparation used for removal of sebum in skin or mucous membrane, improvement of turnover, enhancement of antioxidant function, reduction of acne or fungus.
(11) A kit comprising any one of the above external preparations and an external preparation containing an antioxidant substance or alkaline water.
(12) The kit, wherein the antioxidant is one or more of vitamin Cs, vitamin Es, glutathione and fullerene.
(13) One or more of the following: reduction of moisture transpiration, reduction of blemishes, improvement of sagging, removal of sebum, improvement of turnover, enhancement of antioxidant function, reduction of acne or reduction of fungi in skin or mucous membrane A method comprising the step of applying the external preparation of the present invention to the skin or mucous membrane and then containing an antioxidant or alkaline water which is one or more of vitamin C, vitamin E, glutathione and fullerene The said method using an agent for the said skin or mucous membrane.
(14) A method for preserving the external preparation of the present invention or the external preparation containing an antioxidant or alkaline water which is one or more of vitamin C, vitamin E, glutathione and fullerene, The said method including refrigeration or freezing each external preparation.

  In addition, the present invention also relates to a method for enhancing the health of the skin (improving skin trouble and restoring the health) by using any of the above-mentioned external preparations on intact skin or mucous membrane.

As used herein, “intact skin or mucous membrane” means skin or mucous membrane free from trauma such as a wound. Therefore, “intact skin or mucous membrane” includes skin or mucous membrane that is in a state of moisture transpiration, that has blotches, that has sagging, that has sebum deposits, that has turned over, Skin or mucous membranes that are in an unfavorable state, such as those with a reduced antioxidant function, those with acne, or those with fungi, are included.
Further, “enhancing the soundness of the skin or mucous membrane” means improving each of the above undesirable conditions.

  As described above, in the prior art, it is known that an ozone-dissolved glycerin solution has a bactericidal effect and a wound healing effect. Among these effects, the wound healing effect is due to the bactericidal effect, or the ozone that has penetrated from the wound site stimulates blood cells and promotes the secretion of cytokines such as IL-8. It is believed that. IL-8 is a type of leukocyte chemotactic factor that activates fibroblast induction, angiogenesis, and leukocyte chemotaxis. Cytokines reach the dermis and induce the proliferation of fibroblasts in the dermis. As a result, hyaluronic acid and collagen are generated, and it is thought that wound healing is promoted through the processes of granulation promotion and epithelial regeneration.

  On the other hand, in the intact skin (including mucous membrane) other than the wound surface, in addition to the above action mechanism, a different action mechanism is required. This is because, since the epidermis and dermis are damaged by various situations on the wound surface, the permeation of ozone is easy, whereas in the intact skin, at least the stratum corneum becomes a barrier that prevents the permeation of ozone. Therefore, the external preparation of the present invention exerts an effect when ozone released from the glycerin solution gives mild oxidative stimulation to the stratum corneum and releases cytokines from Langerhans cells and keratinocytes in the stratum corneum by the oxidative stimulation. I think that. In addition, the external preparation of the present invention has a higher concentration of ozone than the conventional ozone-containing lotion, such as an initial ozone concentration of 85 ppm or more, thereby adversely affecting the skin over the long term. Can be achieved without.

(1) According to the external preparation of the present invention, the amount of water transpiration in the skin or mucous membrane, the reduction of stain, the improvement of sagging, the removal of sebum, the improvement of turnover, the enhancement of antioxidant function, the reduction of acne, the fungus Can reduce the health of the skin or mucous membranes.
(2) Among the external preparations of the present invention, those which are cosmetics can enhance the soundness of the skin or mucous membrane and can be used for cosmetic purposes.
(3) Among the external preparations of the present invention, at least one of water, a humectant, a thickener, an antiseptic, a surfactant, an anti-inflammatory agent, ceramide or a precursor thereof, polyethylene glycol, aroma oil, and ethanol is further added. According to the inclusion, the soundness of the skin or mucous membrane can be further enhanced by the effects of these various additional components or the synergistic effect of the components and ozone.
(4) According to the moisturizing agent is at least one of Na hyaluronic acid, acetyl hyaluronic acid Na and derivatives thereof, the thickener is xanthan gum, and the preservative is phenoxyethanol. As a cosmetic liquid, the soundness of the skin or mucous membrane can be further enhanced.
(5) The surfactant is Nauroyl sulfate, the moisturizer is PCA-Na, the anti-inflammatory agent is glycyrrhizic acid 2K, and ceramide or a precursor thereof is ceramide 1, ceramide 3, ceramide 6II, phytosphingosine and When it is at least one kind of cholesterol and the preservative is phenoxyethanol, the soundness of the skin or mucous membrane can be further enhanced as a moisturizing lotion or moisturizing cosmetic liquid.
(6) Among the external preparations of the present invention, according to those further including at least one of polyethylene glycol 450 and polyethylene glycol 65M, the health of skin or mucous membrane can be further enhanced as an ozone cream.
(7) Among the external preparations of the present invention, those further containing ethanol and / or at least one aroma oil are accompanied by a better feeling of use due to the cooling effect of ethanol or at least one aroma oil. The health of skin or mucous membrane can be increased.
(8) According to the external preparation of the present invention, the one further containing water that is acidic water can enhance the soundness of the skin or mucous membrane for a longer period of time.
(9) Among the external preparations of the present invention, according to those used for one or more of the reduction of moisture transpiration, the reduction of blotches and the improvement of sagging in the skin or mucous membrane, these objects are reliably achieved. be able to.
(10) Among the external preparations of the present invention, those used for removal of sebum, improvement of turnover, enhancement of antioxidant function, reduction of acne or reduction of fungi in the skin or mucous membrane have these purposes. Can be reliably achieved.
(11) According to the kit of the present invention comprising one of the above external preparations and an external preparation containing an antioxidant or alkaline water, it is possible to stop the reaction of ozone and prevent excessive oxidation. It becomes. The effect of ozone can be achieved more suitably.
(12) According to the kit of the present invention, the antioxidant is one or more of vitamin Cs, vitamin Es glutathione and fullerene, together with stopping the reaction of ozone, It becomes possible to replenish the antioxidants consumed in the skin. Due to the reducing action of these substances, a more favorable effect can be exerted on the skin or mucous membrane.
(13) According to the method of reducing the amount of water transpiration in the skin or mucous membrane of the present invention, it is possible to supply the antioxidant substance consumed in the skin together with stopping the reaction of ozone. It becomes.
(14) According to the method for preserving the external preparation of the present invention or the external preparation containing one or more of antioxidants or alkaline water, which is one or more of vitamin C, vitamin E, glutathione and fullerene By suppressing the oxidation / reduction reaction of these components, it is possible to preserve the components for a longer period.

The external preparation of the present invention is an external preparation that is used for intact skin or mucous membrane, including an ozone-dissolved glycerin solution, and its formulation, dosage form, etc. are not limited as long as the initial concentration of ozone is at least 85 ppm. Therefore, if the initial concentration of ozone is at least 85 ppm, the external preparation of the present invention may be an ozone-dissolved glycerin solution itself, that is, a solution itself (gel) in which ozone is dissolved in glycerin. Examples of other dosage forms include lotions, cosmetic liquids, creams, milky lotions, cleansings, facial cleansers, UV protection agents, makeup agents, ointments, packs, tapes and patches.
The external preparation of the present invention is preferably used as a cosmetic from the viewpoint of its effect and ease of use.

When ozone is dissolved, a small amount of ozone remaining in the solution as bubbles or ozone remaining in combination with glycerin may be present. Therefore, the concentration of ozone in the external preparation of the present invention means the ratio of ozone dissolved in the final external preparation and present as bubbles or combined with glycerin to the entire external preparation.
In addition, among external preparations having a support such as a patch, the “total external preparation” means the ratio of the external preparation to the entire portion other than the support.

  The concentration of ozone in the external preparation of the present invention is preferably 95 ppm to 1500 ppm, more preferably 100 ppm to 1000 ppm, from the viewpoints of effects and ease of production. These concentrations can be appropriately adjusted according to the application.

In addition, it is preferable that the density | concentration of glycerol in the external preparation of this invention shall be 20% or less normally. By setting the concentration of glycerin to 20% or less, it is possible to suppress irritation of glycerin to the skin or mucous membrane. Therefore, an appropriate diluent can be mixed and diluted with the ozone-dissolved glycerin solution.
As the diluent, those which are not easily degraded by ozone are suitable, and water, polyethylene glycol and the like are suitable.
On the other hand, by making the glycerin concentration 50% or more of the high concentration, a warming effect can be exerted, and the irritability of the high concentration of glycerin can be avoided by washing away after a certain time. . Furthermore, the oxidation reaction by ozone can be stopped by washing away. At this time, it is preferable to use an antioxidant or alkaline water because the oxidation reaction by ozone is more rapidly stopped. In particular, if an antioxidant is used, the antioxidant consumed in the skin can be replenished. As described in Non-Patent Document 1, when vitamin C or vitamin E is applied in advance, when the external preparation of the present invention is applied, ozone is decomposed. If the antioxidant substance is administered after the external preparation is used, the ozone reaction is stopped and the lost antioxidant substance can be replenished together with the predetermined effect of the external preparation of the present invention.

  When water is used as a diluent, it is preferable to use pure water or ultrapure water. By using pure water or ultrapure water, it is possible to suppress the generation of oxides (peroxides) that can be oxidized to ozone and cause irritation to the skin or mucous membrane by impurities or a reduction in the expression of effects. As water, it is more preferable to use water having an acidic pH, that is, acidic water having a pH of less than 7.

  In the present invention, polyethylene glycol may be used. Polyethylene glycol is liquid or solid depending on the molecular weight, and any of them can be used in the present invention. By changing the mixing ratio of two or more types of polyethylene glycol according to the texture at the time of use, it is possible to obtain a texture that is easier to use. Accordingly, the type of polyethylene glycol is not particularly limited, but polyethylene glycol 450 and polyethylene glycol 65M are preferable, and a combination of these is more preferable.

The external preparation of the present invention is typically used as a medicine, quasi drug or cosmetic.
Among the external preparations of the present invention, those used as medicines or quasi drugs may contain various pharmaceutical ingredients or ingredients used in quasi drugs in addition to the ozone-dissolved glycerin solution.

  Further, among the external preparations of the present invention, those used as cosmetics, in addition to the ozone-dissolved glycerin solution, increase the cleanliness, beautification, attractiveness, change the appearance of the human body, or healthy the skin, mucous membrane or hair. Ingredients for keeping may be included.

  Moreover, the external preparation of this invention can express various effects more highly by making it a prescription combined with various raw materials. In particular, conventionally, it has been customary to apply an antioxidant to the skin, and the application of an oxidizing substance has only been used as a peeling agent. However, the external preparation of the present invention can enhance not only the peeling effect as an oxidizing agent but also the immune function of the skin, particularly the antioxidant function, despite the fact that it contains ozone having oxidizing power, and has various effects. Can be expressed. This is due to the fact that ozone gives sustained and mild oxidative stimulation from the glycerin solution. The oxidative stimulation acts on Langerhans cells and keratinocytes in the stratum corneum, and various factors (aging, ultraviolet light, stress, etc.) This is thought to be due to the contribution to the activation of immune function and cell function that were reduced by the above.

  As an additional component used suitably for the external preparation of this invention, water, at least 1 sort (s) of a moisturizer, a thickener, and antiseptic | preservative are mentioned. The external preparation of the present invention containing all these additional components is preferred.

(water)
In the external preparation of the present invention, water is used, for example, for moisturizing or diluting glycerin, and the type thereof is not particularly limited. It is preferable to use acidic water as water because ozone is more suitably stored. The use of acidic soft water prepared using an H-type cation exchange resin is particularly preferred because it can also exhibit an astringent effect and an effect of improving pore opening due to convergence.
As water, pure water or ultrapure water is also preferable as described above. Therefore, acidic pure water is particularly preferable. In addition, by using neutral or acidic water obtained by electrolyzing water, it is possible to further improve the penetration into the skin. Furthermore, acidic water is preferable in that decomposition of ozone is suppressed.

  The amount of water in the external preparation is not limited, and can be appropriately modified within the range of 0 to 99% of the total external preparation for the purpose of relaxing or moisturizing the viscosity of the external preparation of the present invention resulting from glycerin.

(Humectant)
In the external preparation of the present invention, the humectant is used for moisturizing the skin and mucous membrane, and the type thereof is not particularly limited. Any humectant can be used as long as it has a moisturizing action. These components include polyhydric alcohols, NMF (natural moisturizing factor) including PCA-Na (sodium pyrrolidonecarboxylate), hyaluronic acid, acetyl hyaluronic acid Na and derivatives thereof, or salts thereof (sodium salt, potassium salt). Etc.), polysaccharides, polymer agents (thickeners) and the like. The blending amount of the humectant in the external preparation is preferably 0.1 to 1% of the entire external preparation.

  As the humectant, polyhydric alcohols, NMF (natural moisturizing factor) such as PCA-Na, and hyaluronic acid derivatives such as sodium hyaluronate and salts thereof are preferable. Polyethylene glycol is preferable as the polyhydric alcohol, and one or more of them can be used in combination. Polyethylene glycol is preferably polyethylene glycol 450 and polyethylene glycol 65M, and a combination of these is more preferable.

(Thickener)
In the external preparation of the present invention, the thickener is used for adjusting the viscosity of the agent, and the type thereof is not particularly limited. As the thickener, a water-soluble or water-swellable polymer compound is preferable, xanthan gum, gelatin, pectin, agarose, alginate, dextrin, methylcellulose, ethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, Examples thereof include a natural polymer such as a maleic anhydride copolymer, polyacrylic acid and a salt thereof, or a crosslinked product thereof, or a modified product thereof, or a synthetic polymer or a crosslinked product thereof. These polymers may be used alone or in combination of a plurality of polymers. Xanthan gum is most preferred.
Although there is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these thickeners can provide moderate viscosity to an external preparation, 0.1 to 1% of the whole external preparation is preferable.

(Preservative)
In the external preparation of the present invention, the preservative is used for keeping the external preparation clean, and the kind thereof is not particularly limited. Preservatives include phenoxyethanol, paraoxybenzoic acid esters (parabens), benzoic acid, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, chlorcresol, hexachlorophene, resorcin, paraoxyenoxacin, Profloxacin, nalidix, norfloxacin, fleroxacin, ofloxacin. Examples include isopropylmethylphenol, orthophenylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, alkylisoquinolium bromide, trichlorocarbanide, halocarban, photosensitizer 201, triclosan, grape seed extract, benzalkonium hydrochloride, phenol, thymol It is done. Phenoxyethanol is most preferred.
The content of these preservatives with respect to the entire external preparation is not particularly limited as long as the external preparation can be kept clean, but is preferably 0.01 to 1% of the entire external preparation.

  In the external preparation of the present invention, at least one surfactant, anti-inflammatory agent and ceramide or a precursor thereof can also be used. The external preparation of the present invention containing at least one surfactant, anti-inflammatory agent and ceramide or a precursor thereof is preferred.

(Surfactant)
The surfactant is used for dissolving substances that are not mixed with each other in the agent of various components, and the type thereof is not particularly limited.
Surfactants include nonionic surfactants such as sodium lauroyl sulfate and polyoxyethylene sorbitan monooleate, anionic surfactants such as alkyl sulfate salts and sodium normal dodecylbenzene sulfonate, polyoxyethylene dodecyl monomethyl ammonium chloride And a cationic surfactant. Most preferred is sodium lauroyl sulfate.

  The content of these surfactants with respect to the entire external preparation is not particularly limited as long as sufficient solubility can be imparted to each component.

(Anti-inflammatory agent)
Anti-inflammatory agents are used to more effectively suppress inflammation of the skin or mucous membrane, and the type thereof is not particularly limited.
Examples of the anti-inflammatory agent include various steroidal anti-inflammatory agents and non-steroidal agents such as glycyrrhizic acid or a salt thereof, allantoin, or ougon extract. Of these, glycyrrhizic acid and glycyrrhizic acid 2K are preferred, and glycyrrhizic acid 2K is particularly preferred.
There is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these anti-inflammatory agents can suppress inflammation effectively.

(Ceramide or its precursor)
Ceramide and its precursor are the main components that occupy about half of the lipids that fill the gaps between cells in the stratum corneum and connect them together, and they contain abundant moisture and work to prevent the moisture from evaporating. It has the effect of preventing external stimuli and bacteria from entering.
Examples of ceramide or a precursor thereof include ceramide 1, ceramide 2, ceramide 3, ceramide 6II and phytosphingosine, cholesterol and the like, and those containing all of ceramide 1, ceramide 3, ceramide 6II, phytosphingosine and cholesterol are preferable.

  There is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these ceramides or its precursor can have a moisturizing effect and / or an antimicrobial effect.

The external preparation of the present invention is used in combination with an antioxidant and a neutralizing agent for the purpose of reducing or stopping the oxidative action of ozone on the skin by a prescription-free pharmaceutical, quasi-drug, and cosmetics. be able to. In this case, after using the external preparation described in the present method produced from ozone-dissolved glycerin, by administering an antioxidant, the reaction of ozone is stopped in combination with the predetermined effect, and the lost antioxidant It is preferable because the effect that it can be replenished can be obtained.
Antioxidants / neutralizing agents are not limited but include, for example:
・ Vitamin Cs, vitamin Es, vitamins such as selenium,
・ Plant-derived substances such as flavonoids,
・ Carotenoids (α-carotene, β-carotene, γ-carotene), plant-derived antioxidants (SOD-like substances) such as lycopene, xanthophylls, astaxanthins, etc. ・ Terpenes such as flavonoids, ubiquinones, saponins, inositol, catechins, tannins, anthocyanins , Isoflavones,
-Plant-derived polyphenols such as grape seeds, ginkgo biloba leaves, coastal pine bark (Pycnogenol),
Glutathione, diisopropanolamine, diethanolamine (DEA), triisopropanolamine, triethanolamine (TEA), fullerene _(C 60).

Of the antioxidants and neutralizing agents, vitamin Cs, vitamin Es, polyphenols, glutathione and fullerene are preferable, and vitamins C, vitamin E, glutathione and fullerene are particularly preferable.
The content of the antioxidant / neutralizing agent with respect to the entire external preparation is not particularly limited as long as the pH of the external preparation can be suitably maintained.

In the external preparation of the present invention, ethanol or aroma oil can also be suitably used as a cooling agent. Aroma oils include lavender, orange, grapefruit, sandalwood, ylang ylang, peppermint, lemongrass, chamomile roman, rose, rosemary and the like, with lavender oil and rose oil being preferred.
The stability of these components in the external preparation of the present invention is significantly better than in air or water. Therefore, the external preparation of the present invention containing ethanol or aroma oil is preferable because it can provide a longer cooling effect due to these components.

  The content of ethanol or aroma oil with respect to the entire external preparation is not particularly limited as long as the desired effect is exhibited.

  The external preparation of the present invention can contain auxiliary components acceptable to the skin or mucous membrane. Such an auxiliary component is, for example, a stabilizer such as EDTA, paraoxybenzoic acid ester or the like, and the amount thereof is not limited as long as it does not impair the effect of the external preparation of the present invention.

  The external preparation of the present invention is used to make intact skin more healthy, but the ozone concentration during actual use is appropriately diluted according to the age of the subject, the degree of skin health, etc. or the purpose of use. It may be used. Further, although the concentration of ozone in the external preparation of the present invention decreases with time, as long as the initial value of the ozone concentration is 85 ppm or more, the external preparation after such concentration reduction is naturally also included in the external preparation of the present invention. Is included.

The external preparation of the present invention is suitable for reducing the amount of water transpiration, reducing blotches, improving sagging, removing sebum, improving turnover, enhancing antioxidant function, reducing acne or reducing fungi in the skin or mucous membrane. It is preferably used for reducing moisture transpiration, reducing stains and improving sagging, and particularly preferably for reducing stains.
The external preparation of the present invention exerts effects as cosmetics, quasi-drugs, and pharmaceuticals, particularly as cosmetics, by one or more of reducing moisture transpiration, reducing blotches and improving sagging. .

  Regarding the removal of sebum, the external preparation of the present invention makes the sebum hydrophilic by ozone oxidation (unsaturated bonds are converted into carboxyl groups, from poorly soluble to easily soluble), and excessively removed using a strong surfactant or the like. Without any problem, it can be washed only with water, and it can be applied to delicate skin.

  Regarding the improvement of turnover and the removal of dullness, the external preparation of the present invention normalizes the skin turnover by removing old stratum corneum with ozone, the thickened stratum corneum becomes soft, and thus dullness is improved. The skin tone becomes brighter, and it is possible to promote the discharge of melanin.

  Regarding the enhancement of the antioxidant function, the external preparation of the present invention acts on Langerhans cells and keratinocytes that control immunity in the stratum corneum, and can enhance the antioxidant function reduced by various factors. As a result, the external preparation of the present invention improves not only the action on the skin surface but also normalization of cell formation from the skin and the trouble state.

  Acne is caused by the pores of the follicles and sebaceous glands being blocked or narrowed by stratum corneum, and normal sebum secretion is suppressed and sebum stagnation, and bacteria (skin resident bacteria: acne fungus, yellow) Staphylococci) increases, and the lipase of the fungus breaks down triglycerides into free fatty acids, which produce various enzymes and cause inflammation. On the other hand, the external preparation of the present invention adjusts the secretion of sebum by removing the old keratin by mild action due to the sustained release of ozone and adjusting the moisture balance to make excess sebum. On the other hand, it becomes possible to express the effect by ozone-oxidizing and making it hydrophilic, washing gently, and sterilizing acne and atopic disease-causing bacteria and optimizing the pH of the skin.

Although the external preparation of the present invention contains ozone at a high concentration, it can also reduce fungi in intact skin or mucous membrane. Such a reduction effect is due to the bactericidal properties inherent in ozone.
In order to reduce fungi, an antifungal agent may be further added to the external preparation of the present invention. Antifungal agents include bifonazole, clotrimazole, miconazole, itraconazole, fluconazole, flucytosine, amphotericin, pimaricin, micafungin sodium, griseofulvin, exalamide, cyclopyroxolamine, econazole nitrate, oxyconazole nitrate, miconazole nitrate, thioconazole, thioconazole , Roll nitrin.

The external preparation of the present invention can be used in various ways. For example, by using an active ingredient for skin or mucous membranes such as various antioxidants after using the external preparation of the present invention, the active ingredient can be further penetrated and a higher effect can be expressed. More specifically,
(1) After the reaction using the external preparation of the present invention, the reaction is stopped by washing with water (leave-off).
(2) By exfoliating the old stratum corneum according to (1), new cells are exposed and the active ingredient is easily absorbed from the stratum corneum.
(3) After the active ingredient is absorbed by (2), retention of the active ingredient and moisture transpiration are prevented with moisturizing ingredients such as hyaluronic acid, improving cell activation and moisture balance, and protecting the skin from external enemies and irritation ,
Such a series of applications is suitable.

Furthermore, in the external preparation of the present invention, it is possible to select the ozone concentration according to the skin condition. For example, depending on the condition of the skin, it may be assumed that the use of single or multiple external preparations containing ozone in leave-on may lead to excessive oxidation. Can:
(1) Make ozone concentration variable according to skin condition.
(2) Set the reaction time according to the skin condition.
(3) Neutralize cells in an oxidized state by using antioxidant substances (vitamin C, vitamin E, glutathione, fullerene, etc.) and / or alkaline water.

In the external preparation of the present invention, various prescriptions are possible as described above. Such formulations are typically, for example,
・ Prescription to enhance the effect of ozone (prescription containing moisturizer, thickener, preservative, surfactant, anti-inflammatory agent, ceramide or its precursor, polyethylene glycol, etc.)
・ Prescriptions derived from unexpected low reactivity with substances (formulations containing ethanol and aroma oil),
・ Prescription that stabilizes ozone concentration (Prescription using raw materials that can incline acidic water and pH to the acidic side)
Is mentioned.

The external preparation of the present invention may be used as a single external preparation, but it is preferable to use two or more kinds together because there is a synergistic effect. The combined use of three or more external preparations of the present invention is particularly preferred. Such combinations to be used in combination are, for example, lotion and cosmetic liquid, lotion and cream, cosmetic liquid and cream, and lotion, cosmetic liquid and cream. The combination of lotion, essence and cream is particularly preferred. Therefore, what was comprised as a kit of 2 or more types of external preparations among the external preparations of this invention is preferable, and what was comprised as a kit of 3 or more types of external preparations is more preferable.
In addition, use preparations such as cleansing materials and facial cleansers that are less irritating as preparations that can easily achieve the effects of these combinations, and use makeup products such as UV care items and foundations that can further enhance the effects of these combinations. Therefore, those configured as kits are more preferable.
Moreover, as a kit, if the kit which consists of the external preparation of this invention, especially the external preparation containing 1 type, or 2 or more types of cosmetics of this invention, and an antioxidant substance or alkaline water, the oxidation effect by ozone is used. The pH of the skin or mucous membrane can be more suitably adjusted by a combination of the reducing action by an antioxidant or alkaline water. The amount of the external preparation and antioxidant substance or alkaline water to be treated according to the present invention can be appropriately diluted according to the age of the subject, the degree of skin health, etc. or the purpose of use.
As the antioxidant, those described above are used, and a kit in which the antioxidant is one or more of vitamin Cs, vitamin Es and fullerenes is preferable.
As the form of the kit, one or two or more external preparations of the present invention, and if necessary, an external preparation comprising one or two or more antioxidants or alkaline water, respectively, as appropriate in vials, bottles, etc. A container with a use instruction attached as necessary is exemplified.
Antioxidants can be used in the form of, for example, lotions, cosmetic liquids, creams, milky lotions, cleansings, facial cleansers, UV protection agents, makeup agents, ointments, packs, tapes and patches.

The external preparation of the present invention can be produced in the same manner as conventional external preparations using an ozone-dissolved glycerin solution as a raw material. That is, for example, an ozone-dissolved glycerin solution is appropriately diluted with a solvent, and then other components are added as necessary to dissolve or suspend the components.
In addition, an ozone-dissolved glycerin solution is obtained by aeration of ozone microbubbles in glycerin, and those having a desired concentration, particularly those having a high concentration exceeding 100 ppm are typically described in Patent Document 2 or 3. It can be easily prepared by following the method described.

Example 1
The following three products prepared using an ozone-dissolved glycerin solution as a raw material were tested as follows.

The outline of the manufacturing method of the external preparation concerning each Example is as follows. It is clear that those skilled in the art can manufacture the external preparation of the present invention based on such description.
Phenoxyethanol is added to ozone-dissolved glycerin (ozone concentration 2000 ppm), stirred by a homogenizer, and solution A (see below for composition) is added thereto, and further stirred by a homogenizer. Thereafter, PCA-Na is added and stirred again by a homogenizer to obtain a liquid B.
Glycyrrhizic acid 2K is added to ultrapure water, stirred with a homogenizer, and then all of the B liquid is added, ultrapure water is added, and stirred with a homogenizer while warming to obtain an ozone moisturizing lotion (Example 1). .
(Composition of liquid A)
Lauroyl sulfate Na 10ml
Ceramide 1 0.001g
Ceramide 3 0.5g
Ceramide 6II 0.5g
Phytosphingosine 0.5g
Cholesterol 0.5g
Appropriate amount of ultrapure water Total 100ml

Phenoxyethanol is added to ozone-dissolved glycerin, stirred with a homogenizer, then added with xanthan gum, and stirred with a homogenizer. Thereafter, sodium hyaluronate is added and stirred with a homogenizer. Finally, ultrapure water is added, and further stirred with a homogenizer to obtain an ozone moisturizing cosmetic liquid (Example 2).
PEG450 and 500 g of PEG65M are mixed in advance, and ozone-dissolved glycerin (ozone concentration 2000 ppm) is added to the mixture, which is then slowly stirred by a homogenizer to obtain an ozone cream (Example 3).

A 4-week study was conducted on 12 subjects who had been screened in advance. An appropriate amount was used in the order of ozone moisturizing lotion (lotion, Example 1) → ozone moisturizing serum (essence, Example 2) → ozone cream (Example 3) to the right side of the face after washing in the morning and evening. Observations were made at 0, 2, and 4 weeks. The left side was not applied. The appropriate amount was a lotion: 10 yen coin size, essence: 1.5-2 push, cream: spatula, and an amount that fits the entire face. It was used after cleansing the face using the facial cleansing that the test subject normally used. After that, he waited quietly for 25 minutes in the waiting room (humidity 50% ± 15%, room temperature 22 ° C ± 2 ° C). Then, it waited for 5 minutes in the environmental adjustment room (humidity 50% ± 10%, room temperature 22 ° C ± 1 ° C), and measured. The amount of water transpiration was measured with a Tewameter TM300 (manufactured by Integral Co., Ltd.) at a 4 cm portion connecting the base of the subject's earlobe and the lip. Skin elasticity was measured with a Cutometer MPA580 (manufactured by Integral Co., Ltd.) at the same location as the amount of water transpiration. In the spot area analysis, one spot of the photographed spot was digitally analyzed, and the spot area was measured with a digital microscope KH-3000ND (manufactured by Hilox). The results are shown below.
The amount of water transpiration was significantly different after 2 weeks and 4 weeks in the right group. There was no significant difference in the left group. There was a significant difference in elasticity (maximum amplitude) after 4 weeks in both the right and left groups. The elasticity (return rate) was significantly different after 4 weeks in both the right and left groups. There was no significant difference in elasticity (minimum amplitude) in any group. The stain area was significantly different after 2 weeks and 4 weeks compared to before application (Table 2).

About each measurement result, the value before application | coating shall be 100%, It shows below in detail by% value etc. which divided the value after application | coating by the value before application | coating.
The right group of water transpiration was 2 weeks after application (75.3% ± 9.9%) and 4 weeks after application (80.1% ± 21.2%). A significant difference was observed 2 weeks after application and 4 weeks after application. The left group was 2 weeks after application (92.2% ± 20.0%) and 4 weeks after application (108.1% ± 38.3%), and no significant difference was observed. In the comparison between the right group and the left group, a significant difference was observed 2 weeks after application and 4 weeks after application.

  The elasticity (maximum amplitude) was 2 weeks after application (104.7% ± 14.0%) and 4 weeks after application (118.2% ± 26.1%) in the right group. Significant differences were observed 4 weeks after application. The left group was 2 weeks after application (96.8% ± 16.9%) and 4 weeks after application (122.1% ± 21.9%). Significant differences were observed 4 weeks after application. There was no significant difference between the right and left groups.

In the right group, the elasticity (return rate) was 2 weeks after application (106.0% ± 8.2%), 4 weeks after application (118.8% ± 12.7%), and a significant difference was observed 4 weeks after application. The left group was 2 weeks after application (98.3% ± 4.0%) and 4 weeks after application (113.4% ± 12.7%). Significant differences were observed 4 weeks after application. In comparison between the right and left groups, a significant difference was observed 2 weeks after application. Elasticity (minimum amplitude) was 2 weeks after application (93.9% ± 12.1%) and 4 weeks after application (80.3% ± 41.0%) in the right group. There was no significant difference.
The left group was 2 weeks after application (104.9% ± 28.5%) and 4 weeks after application (92.0% ± 30.9%), and no significant difference was observed. There was no significant difference between the right and left groups.

  From the above results, it was clarified that the external preparation of the present invention has an effect of enhancing the health of the skin with respect to the amount of moisture transpiration, elasticity and stains of the skin.

Example 2 Change in ozone concentration when adding ethanol to lotion (I)
(Method)
1. 1 mL of ethanol was added to 10 mL of ozone-containing lotion and stirred with a stirrer for 1 minute (9.1% ethanol).
2. The solution was left at room temperature and the ozone concentration was measured over time.
(result)
As shown in FIGS. 1 and 2, the decrease in ozone concentration was smaller when ethanol was added to the skin lotion. Therefore, there is no problem even if a lotion containing alcohol is used in combination with the external preparation of the present invention. There is no problem in terms of concentration.
The measurement date and indoor temperature and humidity were as follows.

Example 3 Change in ozone concentration when ethanol was added to lotion (II)
(Method)
The ozone concentration was measured over time in the same manner as in Example 2 except that the ethanol concentration was 5%, 10%, and 15%.
(result)
Ethanol concentration had little effect on the degree of ozone concentration decay (Figure 3).
The measurement date and indoor temperature and humidity were as follows.

Example 4 Change in ozone concentration (method) when ethanol was added to a 5% ozone-dissolved glycerin solution
The ozone concentration was measured over time in the same manner as in Example 3 except that a 5% ozone-dissolved glycerin solution was used instead of the skin lotion.
(result)
The lower the ethanol concentration, the less the ozone concentration decayed (FIG. 4).
The measurement date and indoor temperature and humidity were as follows.

Example 5 20% OG Effect of storage temperature on ozone concentration in serum (method)
The ozone concentration was measured over time in the same manner as in Example 3 except that the storage temperature was refrigerated, room temperature or 40 ° C., and ethanol was used as rose oil or lavender oil.
(result)
The lower the storage temperature, the more the decrease in ozone concentration was suppressed (FIGS. 5-7). In addition, ozone concentration was not affected by rose oil or lavender oil at any storage temperature.

Example 6 20% OG Change in ozone concentration when rose oil is added to serum (method)
1. OG was diluted 5 times with purified water, and OG 40 mL + purified water 160 mL = 200 mL was stirred with a stirrer for 5 minutes.
2. The concentration was measured (413.5 ppm, pH 4.45). However, the data of Example 5 was used as a control.
3. Three drops of rose oil were added to the remaining 110 mL.
4). The mixture was shaken and mixed manually for 5 minutes while turning the container so that there was no lump of oil on the surface.
5). Samples were stored in 30 mL portions.
6). Each was stored at room temperature, refrigerated, and 40 ° C., and the change in concentration was measured.
(result)
At any storage temperature, the ozone concentration was not affected by rose oil (FIG. 8).

Example 7 20% OG Change in ozone concentration (method) when lavender oil is added to the serum
1. OG was diluted 5 times with purified water, and OG 20 mL + purified water 80 mL = 100 mL was stirred with a stirrer for 5 minutes.
2. The concentration was measured (413.5 ppm, pH 4.45). However, the data of Example 5 was used as a control.
3. Three drops of lavender oil were added to the remaining 100 mL.
4). The mixture was shaken and mixed manually for 5 minutes while turning the container so that there was no lump of oil on the surface.
5). Samples were stored in 30 mL portions.
6). Each was stored at room temperature, refrigerated, and 40 ° C., and the change in concentration was measured.
(result)
The ozone concentration was not affected by lavender oil (Figure 9).

  The external preparation of the present invention is effectively used as a medicine, a quasi-drug, a cosmetic and the like. Therefore, the present invention greatly contributes to the development of industries related to these.

It is a figure which shows the change of the ozone concentration when ethanol is added to the lotion. It is a figure which shows the ratio of the change of ozone concentration when ethanol is added to lotion. It is a figure which shows the change of the ozone density | concentration when the ethanol which changed the density | concentration is added to the lotion. It is a figure which shows the change of ozone concentration when ethanol is added to a 5% ozone-dissolved glycerin solution. It is a figure which shows the change of the ozone concentration of 20% OG cosmetic liquid in refrigerated storage. It is a figure which shows the change of the ozone density | concentration of 20% OG cosmetic liquid in storage at room temperature. It is a figure which shows the change of the ozone concentration of 20% OG cosmetic liquid in 40 degreeC preservation | save. It is a figure which shows the change of an ozone concentration when rose oil is added to 20% OG cosmetic liquid. It is a figure which shows the change of ozone concentration when lavender oil is added to 20% OG cosmetic liquid.

Claims (14)

  An external preparation for use on intact skin or mucous membrane, comprising an ozone-dissolved glycerin solution, wherein the initial concentration of ozone is at least 85 ppm.   The external preparation according to claim 1, which is a cosmetic.   The external use according to claim 1 or 2, further comprising at least one of water, a humectant, a thickener, a preservative, a surfactant, an anti-inflammatory agent, ceramide or a precursor thereof, polyethylene glycol, aroma oil and ethanol. Agent.   The external preparation according to claim 3, wherein the moisturizing agent is at least one of hyaluronic acid Na, acetyl hyaluronic acid Na and derivatives thereof, the thickener is xanthan gum, and the preservative is phenoxyethanol.   The surfactant is Nalauroyl sulfate, the moisturizer is PCA-Na, the anti-inflammatory agent is glycyrrhizic acid 2K, and the ceramide or precursor thereof is at least ceramide 1, ceramide 3, ceramide 6II, phytosphingosine and cholesterol. The external preparation according to claim 3 or 4, which is one type and the preservative is phenoxyethanol.   The external preparation according to any one of claims 3 to 5, further comprising at least one of polyethylene glycol 450 and polyethylene glycol 65M.   The external preparation according to any one of claims 3 to 6, further comprising ethanol and / or at least one aroma oil.   The external preparation in any one of Claims 3-7 which further contains the water which is acidic water.   The external preparation according to any one of claims 1 to 8, which is used for one or more of reduction of moisture transpiration, reduction of blotches and improvement of sagging in skin or mucous membranes.   The external preparation according to any one of claims 1 to 9, which is used for removal of sebum, improvement of turnover, enhancement of antioxidant function, reduction of acne or fungus in skin or mucous membrane.   The kit which consists of an external preparation in any one of Claims 1-10 and an external preparation containing an antioxidant substance or alkaline water.   The kit according to claim 11, wherein the antioxidant is one or more of vitamin C, vitamin E, glutathione and fullerene.   One or more methods of reducing moisture transpiration in skin or mucous membranes, reducing stains and sagging, removing sebum, improving turnover, enhancing antioxidant function, reducing acne or reducing fungi. Then, after using the external preparation according to any one of claims 1 to 10 on the skin or mucous membrane, an antioxidant or alkaline water which is one or more of vitamin C, vitamin E, glutathione and fullerene The said method using the external preparation containing these for the said skin or mucous membrane.   A method for preserving an external preparation according to any one of claims 1 to 10, or an external preparation containing an antioxidant or alkaline water which is one or more of vitamin C, vitamin E, glutathione and fullerene. The method comprising: refrigeration or freezing each external preparation.

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