Atopic dermatitis treatment

Abstract

[Problem] To provide an agent for improving atopic dermatitis that exhibits a high therapeutic effect and has few side effects on the skin. [Solution] The agent contains erythritol and is characterized by being applied topically to the skin. The agent exhibits a high therapeutic effect on atopic dermatitis and can reduce side effects on the skin. The content of erythritol therein is preferably 0.1-15 wt%. The content of erythritol is especially preferably 1-10 wt%, and a high effect can be obtained thereby.

Description

Technical Field

[0004]

[0001] The present invention relates to an agent for improving atopic dermatitis, and particularly to an agent that exhibits a high therapeutic effect and has few side effects on the skin.

Background Art

[0002] In recent years, along with changes in the living environment, the number of patients with allergic diseases (such as allergic rhinitis, hay fever, bronchial asthma, atopic dermatitis, etc.) has increased, becoming a major problem. In particular, atopic dermatitis is a disease that is common in infants, with an incidence rate of more than 10% in infants, and is likely to be complicated by other atopic diseases as they grow, so it is a disease that causes great anxiety among patients and their families. As shown in Non-Patent Document 1 and Non-Patent Document 2, conventionally, immunosuppressive topical agents and corticosteroid topical agents have been mainly used for the treatment of atopic dermatitis.

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, topical immunosuppressants can cause side effects such as heat, pain, and itching at the application site, and their immunosuppressive effects can also lead to folliculitis, cutaneous mycoses, and other complications. Furthermore, many cases do not show a clear improvement even with the use of topical immunosuppressants, which presents a challenge. In such cases, it is necessary to treat with highly effective topical corticosteroids for a long period of time, but long-term continuous use of topical corticosteroids can cause side effects such as skin atrophy, telangiectasia, acne, and hirsutism, and their use is currently restricted.

[0005] Furthermore, while numerous antihistamines and anti-allergic agents have been used to suppress itching associated with atopic dermatitis, these drugs have side effects such as fatigue and drowsiness, and some are contraindicated for use in pregnant women because they are transferred into breast milk. In other words, conventional treatment methods have presented the challenge of not being able to treat atopic dermatitis until a clear improvement is demonstrated. Given this situation, there was a need to develop an atopic dermatitis treatment that would demonstrate high therapeutic efficacy and have few side effects on the skin and body.

[0006] The object of the present invention is to provide an atopic dermatitis treatment agent that exhibits high therapeutic efficacy and has few side effects on the skin. [Means for solving the problem]

[0007] To achieve the above objective, the atopic dermatitis improving agent according to claim 1 of the present invention contains erythritol, propanediol, and glycerin, with the remainder being water. The above erythritol content is 0.1 by weight % It is characterized by being approximately 15% by weight and being applied topically to the skin. Furthermore, the atopic dermatitis improving agent according to claim 2 is characterized in that the atopic dermatitis improving agent according to claim 1 contains 1 to 10% by weight of erythritol. Furthermore, the atopic dermatitis improving agent according to claim 3 is characterized by further containing vitamin C in the atopic dermatitis improving agent according to claim 1 or claim 2. Furthermore, the atopic dermatitis improving agent according to claim 4 is characterized in that it further contains a vitamin C derivative in the atopic dermatitis improving agent according to claim 1 or claim 2. Furthermore, the atopic dermatitis improving agent according to claim 5 is characterized in that, in the atopic dermatitis improving agent described in claim 4, it contains 0.01% by weight or more of a vitamin C derivative. Furthermore, the atopic dermatitis improving agent according to claim 6 is characterized in that it contains 0.05% by weight or more of a vitamin C derivative, in addition to the atopic dermatitis improving agent described in claim 5. Furthermore, the atopic dermatitis improving agent according to claim 7 is characterized in that, in the atopic dermatitis improving agent according to claim 4, the vitamin C derivative is any of magnesium ascorbyl phosphate, sodium ascorbyl phosphate, trisodium ascorbyl palmitate phosphate, or 2-glucoside of ascorbic acid. Furthermore, the atopic dermatitis improving agent according to claim 8 is characterized in that it further contains vitamin B group or vitamin D group in the atopic dermatitis improving agent according to claim 3. Furthermore, the atopic dermatitis improving agent according to claim 9 is characterized in that it further contains B vitamins and D vitamins in the atopic dermatitis improving agent described in claim 3. Furthermore, the atopic dermatitis improving agent according to claim 10 is characterized in that it further contains B vitamins or D vitamins in the atopic dermatitis improving agent described in claim 4. Furthermore, the atopic dermatitis improving agent according to claim 11 is characterized in that it further contains B vitamins and D vitamins in the atopic dermatitis improving agent described in claim 4. [Effects of the Invention]

[0008] As described above, the atopic dermatitis improving agent according to claim 1 of the present invention contains erythritol and is applied topically to the skin, thus exhibiting a high therapeutic effect and minimizing side effects on the skin. Furthermore, the atopic dermatitis improving agent according to claim 2 can further enhance the therapeutic effect because, in addition to the atopic dermatitis improving agent described in claim 1, the erythritol content is 0.1 to 15% by weight. Furthermore, according to the atopic dermatitis improving agent of claim 3, the erythritol content in the atopic dermatitis improving agent described in claim 2 is 1 to 10% by weight, which can further enhance the therapeutic effect. Furthermore, according to the atopic dermatitis improving agent of claim 4, since the atopic dermatitis improving agent described in any of claims 1 to 3 further contains vitamin C, the therapeutic effect can be further enhanced. Furthermore, according to the atopic dermatitis improving agent of claim 5, the atopic dermatitis improving agent described in any of claims 1 to 3 further contains a derivative of vitamin C, thereby further enhancing the therapeutic effect. Furthermore, according to the atopic dermatitis improving agent of claim 6, the atopic dermatitis improving agent described in claim 5 contains 0.01% by weight or more of a vitamin C derivative, which can further enhance the therapeutic effect. Furthermore, according to the atopic dermatitis improving agent of claim 7, the atopic dermatitis improving agent described in claim 6 contains 0.05% by weight or more of a vitamin C derivative, which can further enhance the therapeutic effect. Furthermore, according to the atopic dermatitis improving agent of claim 8, the atopic dermatitis improving agent described in claim 4 further contains B vitamins or D vitamins, which can further enhance the therapeutic effect. Furthermore, according to the atopic dermatitis improving agent of claim 9, the atopic dermatitis improving agent described in claim 4 further contains B vitamins and D vitamins, which can further enhance the therapeutic effect. Moreover, according to the atopic dermatitis improving agent according to claim 10, in the atopic dermatitis improving agent according to claim 5, since it further contains vitamin B group or vitamin D group, the therapeutic effect can be further enhanced. Moreover, according to the atopic dermatitis improving agent according to claim 11, in the atopic dermatitis improving agent according to claim 5, since it further contains vitamin B group and vitamin D group, the therapeutic effect can be further enhanced.

Brief Description of the Drawings

[0009] [Figure 1] It is a photograph showing the atopic dermatitis improving effect (clinical photograph) according to Example 1 of the mode for carrying out the present invention. [Figure 2] It is a photograph showing the atopic dermatitis improving effect (clinical photograph) according to Example 1 of the mode for carrying out the present invention. [Figure 3] It is a photograph showing the atopic dermatitis improving effect (clinical photograph) according to Example 1 of the mode for carrying out the present invention. [Figure 4] It is a photograph showing the atopic dermatitis improving effect (clinical photograph) according to Example 2 of the mode for carrying out the present invention.

Mode for Carrying Out the Invention

[0010] Hereinafter, the mode for carrying out the present invention will be described while referring to FIGS. 1 to 4. Note that the examples described in this specification do not particularly limit the present invention. The atopic dermatitis improving agent according to this embodiment contains erythritol as an active ingredient. The erythritol used in the present invention is a tetrahydric sugar alcohol, which is contained in natural foods such as lichens, mushrooms, and fruits, and is a highly safe material. Regarding the production method of erythritol, it can be divided into a chemical synthesis method and a fermentation method, but most are produced by fermentation with yeast using glucose as a raw material.

[0011] The content of erythritol in the atopic dermatitis improving agent of the present invention is preferably 0.1 to 15% by weight, particularly preferably 1 to 10% by weight, based on the total amount of the composition. If it is less than 1% by weight, although there is an effect, the effect is reduced. If it exceeds 10% by weight, although there is also an effect, the solubility becomes poor, and a situation unfavorable for preparing a topical agent occurs. If it is less than 0.1% by weight, no effect can be seen. If erythritol increases more than 15% by weight, it will crystallize and cannot be used as an atopic dermatitis improving agent.

[0012] Atopic dermatitis is a skin disease confirmed not only in humans but also in many animals (such as dogs, cats, horses, mice, etc.). Also, its pathogenesis has many common points across animal species, such as a decrease in the skin barrier function and the invasion of allergens into the body. Therefore, examples of organisms to which the present invention can be applied include, in addition to humans, pet animals such as dogs, cats, horses, mice, etc.

[0013] When administering the atopic dermatitis improving agent of the present invention to a living body, it may be administered as it is, but it is preferably provided by being formulated into a topical skin composition together with appropriate additives within a range that does not impair the effects of the present invention. The topical skin agents of the present invention include pharmaceuticals, quasi-drugs, cosmetics, etc.

[0014] The dosage form of the pharmaceuticals, quasi-drugs, and cosmetics containing the atopic dermatitis improving agent of the present invention is not particularly limited as long as the effects of the present invention are not impaired. For example, any dosage form used for topical skin agents such as sprays, ointments, lotions, and creams can be applied. As the base used for these topical skin agents, known ones or those newly provided in the future can be used, and there is no particular limitation. For example, petrolatum, castor oil, silicone, squalane, sodium acrylate, behenyl alcohol, glyceryl monostearate, stearyl alcohol, ethanol, butyl alcohol, phenoxyethanol, 1,3-butylene glycol, isopropyl myristate, stearic acid, lecithin, and purified water, etc. can be mentioned, and they can be used alone or in combination of two or more.

[0015] In addition to the above-mentioned base components, the atopic dermatitis improving agent of the present invention may appropriately contain various additives that are permissible in the manufacture of pharmaceuticals, quasi-drugs, and cosmetics, provided that they do not impair the effects of the present invention, namely, antioxidants, preservatives, humectants, viscosity enhancers, buffers, adsorbents, solvents, emulsifiers, and stabilizers.

[0016] In this invention, "effect of improving atopic dermatitis" means the improvement effect that can be brought about by a topical skin agent in subjects (including humans and other non-human animals) to which the agent is administered, such as improvement of characteristic symptoms of atopic dermatitis, such as erythema, lichenification, inflammation, abrasions, scab formation, and cell infiltration into the dermis layer of the skin. [Examples]

[0017] The present invention will be described in more detail below with reference to Examples 1 to 3. However, the present invention is not limited to these.

[0018] [Example 1] The following are examples of prescriptions 1 to 7 of the atopic dermatitis treatment agents used in the study. The units are given as the amount (by weight) of the ingredient per 100 ml (100 g). Formula Example 1 contains 0.1% by weight of erythritol. Formula Example 2 contains 0.5% by weight of erythritol. Formula Example 3 contains 1% by weight of erythritol. Formula Example 4 contains 5% by weight of erythritol. Formula Example 5 contains 10% by weight of erythritol. Formula Example 6 contains 12% by weight of erythritol. Formula Example 7 and Formula Example 7' contain 15% by weight of erythritol. Formula Example 7' is a follow-up of Formula Example 7. As mentioned earlier, if the erythritol content exceeds 15% by weight, it will crystallize, making it unsuitable for use as an atopic dermatitis treatment agent. For comparison, we prepared comparative formulations 1-3 that do not contain erythritol. Comparative formulation 1 does not contain erythritol. Comparative formulation 2 contains sorbitol, a sugar alcohol that belongs to the same carbohydrate category as erythritol, instead of erythritol. Comparative formulation 3 contains only magnesium ascorbyl phosphate. For the atopic dermatitis improving agent in Prescription Example 1, 0.1g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 2, 0.5g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total weight reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 3, 1.0 g of erythritol, 5.0 g of propanediol, and 2.0 g of glycerin were placed in a container, and purified water was added until the total weight reached 100 g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 4, 5.0g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total weight reached 100g. The agent was then dissolved while stirring to prepare the improving agent for the test. For the atopic dermatitis improving agent in Prescription Example 5, 10.0g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total weight reached 100g. The agent was then dissolved while stirring to prepare the improving agent for the test. For the atopic dermatitis improving agent in Prescription Example 6, 12.0g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 7, 15.0g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 7', 15.0g of erythritol, 5.0g of propanediol, and 2.0g of glycerin were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For comparative formulation example 1, 5.0 g of propanediol and 2.0 g of glycerin were placed in a container, and purified water was added until the total amount reached 100 g. The mixture was then stirred and dissolved to prepare the agent to be used in the test. For comparative formulation example 2, 10.0 g of sorbitol, 5.0 g of propanediol, and 2.0 g of glycerin were placed in a container, and purified water was added until the total amount reached 100 g. The mixture was then stirred and dissolved to prepare the agent to be used in the test. For comparative formulation example 3, 0.05 g of magnesium ascorbyl phosphate, 5.0 g of propanediol, and 2.0 g of glycerin were placed in a container, and purified water was added until the total amount reached 100 g. The mixture was then stirred and dissolved to prepare the agent to be used in the test.

[0019] (Prescription example 1) (Ingredients) (Weight%) Erythritol 0.1 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0020] (Prescription example 2) (Ingredients) (Weight%) Erythritol 0.5 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0021] (Prescription example 3) (Ingredients) (Weight%) Erythritol 1.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0022] (Prescription example 4) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0023] (Prescription example 5) (Ingredients) (Weight%) Erythritol 10.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0024] (Prescription example 6) (Ingredients) (Weight%) Erythritol 12.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0025] (Prescription example 7) (Ingredients) (Weight%) Erythritol 15.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder (Prescription example 7') (Ingredients) (Weight%) Erythritol 15.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0026] (Comparative prescription example 1) (Ingredients) (Weight%) Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0027] (Comparative prescription example 2) (Ingredients) (Weight%) Sorbitol 10.0 Propanediol 5.0 Glycerin 2.0 Purified water remainder

[0028] (Comparative prescription example 3) (Ingredients) (Weight%) Magnesium ascorbyl phosphate 0.05 Propanediol 5.0 Glycerin 2.0 Purified water remainder In addition, in formulation examples 1 to 7, formulation example 7', and comparative formulation examples 1 to 3, "Erythritol" manufactured by Mitsubishi Chemical Foods Corporation was used as erythritol, "Zemear Select Propanediol" manufactured by DuPont Ltd. was used as propanediol, and "Cosmetic-grade Concentrated Glycerin" manufactured by Sakamoto Pharmaceutical Co., Ltd. was used as glycerin. Furthermore, tap water or groundwater filtered through a membrane filter was used as purified water.

[0029] The effectiveness of the products in prescription examples 1-7, prescription example 7', and comparative prescription examples 1-3 in improving atopic dermatitis was evaluated. The study included 86 dogs diagnosed with atopic dermatitis according to general diagnostic criteria (Favrot C et al., Vet Dermatol. 21: 23-30. 2010) (mean CADSESI score: 59.2 ± 22.2). Each product shown in the prescription examples was filled into a spray bottle, and 2-3 ml per spray was applied to the affected area 3-5 times a day. The effect was then evaluated after 2 weeks. In addition, the CADESI score was used to score the degree of improvement in atopic dermatitis (CADESI score; Olivry, T et al., J. Dermatol. Treat., 8:243-247. 1997). The CADESI score is an evaluation criterion that divides the dog's body surface into 20 areas and scores the degree of the three common clinical symptoms of atopic dermatitis (erythema, lichenification, and inflammation or abrasion) in each area from 0 (none) to 3 (severe). Therefore, the most severe case would be 180 points (3 × 3 × 20). The evaluation results for prescription examples 1 to 7 are shown in Tables 1 and 2, the evaluation results for prescription example 7' are shown in Table 2-1, and the evaluation results for comparative prescription examples 1 to 3 are shown in Table 3. The evaluation criteria used in Tables 1 and 3 are shown below. EXCELLENT: Individuals whose CADESI score decreased by more than 20% from their score before the start of the test after the test. GOOD: Individuals whose CADESI score after the test decreased by 10% to less than 20% compared to their score before the test. FAIR: Individuals whose CADESI score after the test decreased by 0% to less than 10% compared to their score before the test. POOR: Individuals whose CADESI score increased after the end of the test. Furthermore, in this study, individuals whose CADESI score decreased by 10% or more from their score before the start of the study (EXCELLENT + GOOD) were considered to have shown improvement, and the improvement rate (%) was calculated using the following formula. Improvement rate (%) = {(Number of individuals showing improvement) / (Number of individuals used in the experiment)} × 100

[0030] [Table 1]

[0031] [Table 2] [Table 2-1]

[0032] [Table 3]

[0033] As shown in Tables 1 and 2, the improvement rate was 20% for Formula Example 1 containing 0.1% by weight of erythritol, 23.08% for Formula Example 2 containing 0.5% by weight of erythritol, 30.0% for Formula Example 3 containing 1.0% by weight of erythritol, 33.33% for Formula Example 4 containing 5.0% by weight of erythritol, 36.36% for Formula Example 5 containing 10.0% by weight of erythritol, 25% for Formula Example 6 containing 12% by weight of erythritol, 33.33% for Formula Example 7 containing 15% by weight of erythritol, and 20% for Formula Example 7'. Furthermore, no side effects from topical application were observed in any of the formulations. Furthermore, prescription example 7' is a follow-up to prescription example 7, but the improvement rate is lower compared to prescription examples 2 through 6. Table 3 shows the results for comparative prescription examples 1-3. The improvement rate was 0% for comparative prescription example 1 and comparative prescription example 2, and 9.09% for comparative prescription example 3, which is significantly lower than the improvement rates for prescription examples 1-7.

[0034] Representative clinical photographs from individuals who showed improvement in this study are shown in Figures 1 to 3. Figure 1 shows the condition of the paw of a dog with canine atopic dermatitis before and one day after the start of the trial using prescription example 3. In this case, it can be seen that the inflammation was suppressed and more hair began to grow after one day compared to before the start of the trial. Figure 2 shows the condition of the abdomen of a dog with canine atopic dermatitis before and 2 days after the start of the study using prescription example 4. In this case, it can be seen that the inflammation was suppressed and more hair began to grow after 2 days compared to before the start of the study. Figure 3 shows the condition of the abdomen of a dog with canine atopic dermatitis before and 4 days after the start of the study using prescription example 5. In this case, it can be seen that the inflammation was suppressed and more hair began to grow after 4 days compared to before the start of the study.

[0035] As described above, the present invention is an atopic dermatitis treatment agent containing erythritol as an active ingredient, and therefore has a high therapeutic effect. In addition, since erythritol is not a pharmaceutical ingredient but an ingredient that is commonly used in cosmetics, health foods, and general foods, it can cause fewer side effects on the skin compared to topical adrenal lipid steroids and the like.

[0036] [Example 2] Next, Example 2 will be described. The atopic dermatitis improving agent according to this Example 2 contains vitamin C or a derivative thereof as an active ingredient, along with the erythritol used in Example 1. By using vitamin C or a derivative thereof in combination, a higher atopic dermatitis improving effect can be obtained. Examples of vitamin C include ascorbic acid, and examples of vitamin C derivatives include ascorbic acid phosphate esters, ascorbic acid fatty acid esters, ascorbic acid glucoside and other glycosides of ascorbic acid and their salts. Examples of salts of vitamin C or vitamin C derivatives include sodium salts, potassium salts, calcium salts, magnesium salts, and ammonium salts. More specifically, examples of vitamin C derivatives that can be preferably used in the present invention include magnesium ascorbyl phosphate, trisodium ascorbyl palmitate phosphate, sodium ascorbate phosphate, aminoprolyl ascorbate phosphate, ascorbic acid glucoside, ascorbyl palmitate, ascorbyl stearate, and sodium ascorbate sulfate. These vitamin C derivatives may be used individually or in combination of two or more.

[0037] The atopic dermatitis-improving effect of the atopic dermatitis-improving agent in Example 2 was evaluated using the products of Formula Example 8, Formula Example 9, and Comparative Formula Examples 1-3. The results are shown in Table 4. Furthermore, the effectiveness of the atopic dermatitis-improving agents in prescription examples 8-1, 8-2, 8-3, and 8-4 in improving atopic dermatitis was also evaluated. The results are shown in Table 4-1. Formulation Examples 8 and 9 of this Example 2 are shown below. Note that comparative formulation examples 1 to 3 are the same as in Example 1. For the atopic dermatitis improving agent in Prescription Example 8, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 0.05g of magnesium ascorbyl phosphate (vitamin C derivative) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in Prescription Example 8-1, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 0.01g of magnesium ascorbyl phosphate (vitamin C derivative) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test. For the atopic dermatitis improving agent in prescription example 8-2, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 0.1g of magnesium ascorbyl phosphate (vitamin C derivative) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for the test. For the atopic dermatitis improving agent in prescription example 8-3, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 1g of magnesium ascorbyl phosphate (vitamin C derivative) were placed in a container, and purified water was added until the total weight reached 100g. The agent was then dissolved while stirring to prepare the improving agent for the test. For the atopic dermatitis improving agent in prescription example 8-4, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 5g of magnesium ascorbyl phosphate (vitamin C derivative) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for the test. For the atopic dermatitis improving agent in Prescription Example 9, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, and 0.05g of ascorbic acid (vitamin C) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent for use in the test.

[0038] (Prescription example 8) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.05 Purified water remainder (Prescription example 8-1) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.01 Purified water remainder (Prescription example 8-2) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.1 Purified water remainder (Prescription example 8-3) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 1.0 Purified water remainder (Prescription example 8-4) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 5.0 Purified water remainder

[0039] (Prescription example 9) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Ascorbic acid (Vitamin C) 0.05 Purified water remainder In addition, in formulation examples 8, 8-1, 8-2, 8-3, 8-4, and formulation example 9, "Erythritol" manufactured by Mitsubishi Chemical Foods Corporation was used as erythritol, "Zemear Select Propanediol" manufactured by DuPont Ltd. was used as propanediol, "Cosmetic-grade Concentrated Glycerin" manufactured by Sakamoto Pharmaceutical Co., Ltd. was used as glycerin, "Amitose DGA" manufactured by Seiwa Kasei Co., Ltd. was used as the vitamin C derivative magnesium ascorbyl phosphate, and "Magnesium L-Ascorbyl Phosphate" manufactured by Fujifilm Wako Pure Chemical Industries Ltd. was used as the vitamin C ascorbic acid. Furthermore, tap water or groundwater filtered through a membrane filter was used as purified water.

[0040] [Table 4] [Table 4-1]

[0041] Formula example 8, which contained 5% by weight of erythritol and 0.05% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), showed an improvement rate of 80%. The formulation in example 8-1, which contained 5% by weight of erythritol and 0.01% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), showed a 50% improvement rate. The formulation in example 8-2, which contained 5% by weight of erythritol and 0.1% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), showed an improvement rate of 88.9%. The formulation in example 8-3, which contained 5% by weight of erythritol and 1% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), showed an improvement rate of 83.3%. The formulation in example 8-4, which contained 5% by weight of erythritol and 5% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), showed an improvement rate of 80%. The formulation in example 9, which contained 5% by weight of erythritol and 0.05% by weight of vitamin C (ascorbic acid), showed a 70% improvement rate. It was confirmed that adding 0.01% or more by weight of a vitamin C derivative (magnesium ascorbyl phosphate) can enhance the effect, and adding 0.05% or more by weight can further enhance the effect. It was also confirmed that adding 0.05% or more by weight of vitamin C (ascorbic acid) can enhance the effect. Furthermore, no side effects from topical application were observed in the prescribed cases.

[0042] Figure 4 shows representative clinical photographs from individuals who showed improvement in the results of this study. Figure 4 shows the condition of the paw of a dog with canine atopic dermatitis before and one day after the start of the trial for prescription example 8. In this case, it can be seen that the inflammation was suppressed and more hair began to grow after one day compared to before the start of the trial.

[0043] Thus, combining erythritol with vitamin C or a vitamin C derivative can demonstrate further improvement in atopic dermatitis. Furthermore, erythritol, the aforementioned vitamin C, and vitamin C derivatives are not pharmaceutical ingredients, but rather ingredients commonly found in cosmetics, health foods, and general foods on the market, thus minimizing skin side effects.

[0044] [Example 3] Next, Example 3 will be described. The atopic dermatitis improving agent according to this Example 3 is made by adding vitamins from the B vitamin group and / or vitamin D group, along with erythritol and vitamin C or its derivatives used in Example 2. This allows for an even higher effect to be expected. Examples of B vitamins include vitamin B1, vitamin B2, niacin (nicotinic acid and nicotinamide), pantothenic acid, panthenol, vitamin B6 (pyridoxine, pyridoxal and pyridoxamine), biotin, folic acid, and vitamin B12 (cyanocobalamin, hydroxocobalamin, methylcobalamin and adenosylcobalamin). Examples of vitamin D group include cholecalciferol (vitamin D3), ergocalciferol (vitamin D2), dihydrocalciferol, dihydrotachisterol, alfacalcidol, calcitriol, etc.

[0045] The effectiveness of the atopic dermatitis improving agent of this Example 3 in improving atopic dermatitis was evaluated using the products of Prescription Examples 10 to 18 and Comparative Prescription Examples 1 to 3. The results are shown in Tables 5 to 7. The formulation example for this Example 3 is shown below. Furthermore, comparative formulation examples 1 to 3 are the same as those in Examples 1 and 2 described above. Furthermore, for the atopic dermatitis improving agent in prescription example 10, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of magnesium ascorbyl phosphate (vitamin C derivative), 0.05g of panthenol (vitamin B), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 11, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of magnesium ascorbyl phosphate (vitamin C derivative), and 0.05g of panthenol (vitamin B) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 12, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of magnesium ascorbyl phosphate (vitamin C derivative), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 13, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of ascorbic acid (vitamin C), 0.05g of cholecalciferol (vitamin D), and 0.05g of panthenol (vitamin B) were placed in a container, and purified water was added until the total amount reached 100g. The improving agent to be used in the test was prepared by dissolving the ingredients while stirring. Furthermore, for the atopic dermatitis improving agent in prescription example 14, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of ascorbic acid (vitamin C), and 0.05g of panthenol (vitamin B) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 15, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of ascorbic acid (vitamin C), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 16, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of sodium ascorbyl phosphate (vitamin C derivative), 0.05g of panthenol (vitamin B), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 17, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of trisodium ascorbyl palmitate phosphate (vitamin C derivative), 0.05g of panthenol (vitamin B), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The mixture was then stirred and dissolved to prepare the improving agent to be used in the test. Furthermore, for the atopic dermatitis improving agent in prescription example 18, 5.0g of erythritol, 5.0g of propanediol, 2.0g of glycerin, 0.05g of ascorbic acid 2-glucoside (vitamin C derivative), 0.05g of panthenol (vitamin B), and 0.05g of cholecalciferol (vitamin D) were placed in a container, and purified water was added until the total amount reached 100g. The agent was then dissolved while stirring to prepare the improving agent to be used in the test.

[0046] (Prescription example 10) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.05 Panthenol (Vitamin B) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder

[0047] (Prescription example 11) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.05 Panthenol (Vitamin B) 0.05 Purified water remainder

[0048] (Prescription example 12) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Magnesium ascorbyl phosphate (vitamin C derivative) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder

[0049] (Prescription example 13) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Ascorbic acid (Vitamin C) 0.05 Cholecalciferol (Vitamin D) 0.05 Panthenol (Vitamin B) 0.05 Purified water remainder

[0050] (Prescription example 14) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Ascorbic acid (Vitamin C) 0.05 Panthenol (Vitamin B) 0.05 Purified water remainder

[0051] (Prescription example 15) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Ascorbic acid (Vitamin C) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder (Prescription example 16) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Sodium ascorbyl phosphate (vitamin C derivative) 0.05 Panthenol (Vitamin B) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder (Prescription example 17) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Sodium Ascorbyl Palmitate Phosphate (Vitamin C derivative) 0.05 Panthenol (Vitamin B) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder (Prescription example 18) (Ingredients) (Weight%) Erythritol 5.0 Propanediol 5.0 Glycerin 2.0 Ascorbic acid 2-glucoside (vitamin C derivative) 0.05 Panthenol (Vitamin B) 0.05 Cholecalciferol (Vitamin D) 0.05 Purified water remainder In addition, in prescription examples 10 to 18, the following were used: "Erythritol" manufactured by Mitsubishi Chemical Foods Corporation as erythritol, "Zemear Select Propanediol" manufactured by DuPont Ltd. as propanediol, "Cosmetic-grade Concentrated Glycerin" manufactured by Sakamoto Pharmaceutical Co., Ltd. as glycerin, "Amitose DGA" manufactured by Seiwa Kasei Co., Ltd. as magnesium ascorbyl phosphate (vitamin C derivative), "Ascorbic Acid PS" manufactured by Showa Denko K.K. as sodium ascorbyl phosphate (vitamin C derivative), "Apprecie®" manufactured by Showa Denko K.K. as trisodium ascorbyl palmitate phosphate (vitamin C derivative), "Ascofresh®" manufactured by Hayashibara Co., Ltd. as 2-glucoside (vitamin C derivative), "Magnesium L-ascorbyl phosphate" manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. as ascorbic acid (vitamin C), "D-Pantothenyl Alcohol" manufactured by DSM Co., Ltd. as panthenol (vitamin B), and "Cholecalciferol" manufactured by Tokyo Chemical Industry Co., Ltd. as cholecalciferol (vitamin D). Furthermore, tap water or groundwater filtered through a membrane filter was used as purified water.

[0052] [Table 5]

[0053] [Table 6] [Table 7]

[0054] The improvement rate for prescription example 10, which contained 5% by weight of erythritol, 0.05% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), 0.05% by weight of a B vitamin (panthenol), and 0.05% by weight of a vitamin D group (cholecalciferol), was 90.9%. The improvement rate for prescription example 11, which contained 5% by weight of erythritol, 0.05% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), and 0.05% by weight of a B vitamin (panthenol), was 82%. The improvement rate for prescription example 12, which contained 5% by weight of erythritol, 0.05% by weight of a vitamin C derivative (magnesium ascorbyl phosphate), and 0.05% by weight of a vitamin D group (cholecalciferol), was 80%.

[0055] The improvement rate for prescription example 13, which contained 5% by weight of erythritol, 0.05% by weight of ascorbic acid (vitamin C), 0.05% by weight of vitamin B group (panthenol), and 0.05% by weight of vitamin D group (cholecalciferol), was 70%. The improvement rate for prescription example 14, which contained 5% by weight of erythritol, 0.05% by weight of vitamin C (ascorbic acid), and 0.05% by weight of vitamin B group (panthenol), was 72.73%. The improvement rate for prescription example 15, which contained 5% by weight of erythritol, 0.05% by weight of ascorbic acid (vitamin C), and 0.05% by weight of vitamin D group (cholecalciferol), was 78%.

[0056] The improvement rate for prescription example 16, which contained 5% by weight of erythritol, 0.05% by weight of sodium ascorbyl phosphate (vitamin C derivative), 0.05% by weight of vitamin B group (panthenol), and 0.05% by weight of vitamin D group (cholecalciferol), was 91.7%. The improvement rate for prescription example 17, which contained 5% by weight of erythritol, 0.05% by weight of trisodium ascorbyl palmitate phosphate (vitamin C derivative), 0.05% by weight of vitamin B group (panthenol), and 0.05% by weight of vitamin D group (cholecalciferol), was 100%. The improvement rate for prescription example 18, which contained 5% by weight of erythritol, 0.05% by weight of ascorbic acid 2-glucoside (vitamin C derivative), 0.05% by weight of vitamin B group (panthenol), and 0.05% by weight of vitamin D group (cholecalciferol), was 90%. It was confirmed that adding 0.05% or more of vitamin B group (panthenol) and vitamin D group (cholecalciferol) can enhance their effects. Furthermore, no side effects from topical application were observed in the prescribed cases.

[0057] Thus, by adding B vitamins and / or vitamin D vitamins to a formulation that combines erythritol with vitamin C or a vitamin C derivative, it is possible to achieve further improvement in atopic dermatitis. Furthermore, by combining erythritol and a vitamin C derivative with B vitamins and / or vitamin D vitamins, a significant improvement in atopic dermatitis can be achieved, and the effect is particularly remarkable when B vitamins and vitamin D vitamins are included. Furthermore, erythritol, vitamin C or vitamin C derivatives, B vitamins, and vitamin D are not pharmaceutical ingredients, but rather ingredients commonly found in cosmetics, health foods, and general foods on the market, thus minimizing skin side effects. [Industrial applicability]

[0058] The present invention relates to an agent for improving atopic dermatitis, and more particularly to one that exhibits high therapeutic efficacy and is designed to minimize skin side effects, and is suitable, for example, for use as an agent for improving atopic dermatitis in humans.

Claims

1. It contains erythritol, propanediol, and glycerin. The remainder is water. The erythritol content is 0.1% to 15% by weight. An atopic dermatitis treatment agent characterized by its application to the skin.

2. In the atopic dermatitis improving agent according to claim 1, An atopic dermatitis treatment agent characterized by containing 1 to 10% by weight of erythritol.

3. In the atopic dermatitis improving agent according to claim 1 or claim 2, An atopic dermatitis treatment agent characterized by further containing vitamin C.

4. In the atopic dermatitis improving agent according to claim 1 or claim 2, An atopic dermatitis treatment agent characterized by further containing a vitamin C derivative.

5. In the atopic dermatitis improving agent according to claim 4, An atopic dermatitis treatment agent characterized by containing 0.01% by weight or more of a vitamin C derivative.

6. In the atopic dermatitis improving agent according to claim 5, An atopic dermatitis treatment agent characterized by containing 0.05% by weight or more of a vitamin C derivative.

7. In the atopic dermatitis improving agent according to claim 4, The above-mentioned vitamin C derivative is characterized by being one of magnesium ascorbyl phosphate, sodium ascorbyl phosphate, trisodium ascorbyl palmitate phosphate, or 2-glucoside of ascorbic acid, and is an agent for improving atopic dermatitis.

8. In the atopic dermatitis improving agent according to claim 3, An agent for improving atopic dermatitis, characterized by further containing B vitamins or D vitamins.

9. In the atopic dermatitis improving agent according to claim 3, An agent for improving atopic dermatitis, characterized by further containing B vitamins and D vitamins.

10. In the atopic dermatitis improving agent according to claim 4, An agent for improving atopic dermatitis, characterized by further containing B vitamins or D vitamins.

11. In the atopic dermatitis improving agent according to claim 4, An agent for improving atopic dermatitis, characterized by further containing B vitamins and D vitamins.

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