KR102368646B1 - Atopy treatment lotion utilizing room temperature emulsifying process - Google Patents

Abstract

The present invention is to provide a lotion and a manufacturing method for improving atopic dermatitis using a room temperature emulsification process, and the configuration of the present invention is purified water; ammonium acryloyldimethyltaurate/VPicopolymer as thickener; Emulsifiers polyglyceryl-4 caprate, polyglyceryl-3 ricinoleate; Evening primrose extract; Evening primrose oil; self-inflicted extract; Self-inflicted oil; formed by mixing the purified water 3 to 75% by weight, evening primrose extract 0.01 to 50% by weight, self-inflicted extract 0.01 to 50% by weight, evening primrose oil 0.01 to 40% by weight, self-inflicted oil 0.01 to 40% by weight, Polyglyceryl It is characterized in that it is formed by mixing 0.01 to 15 wt% of -4 Caprate, 0.1 to 15 wt% of Polyglyceryl-3 Ricinoleate, and 0.01 to 15 wt% of Ammonium acryloyldimethyltaurate/VP copolymer.

Description

Atopy treatment lotion utilizing room temperature emulsifying process

The present invention relates to atopic improvement lotion using a room temperature emulsification process, and more specifically, room temperature emulsification of a new composition that can effectively treat atopy without destruction of components useful for atopy treatment using room temperature emulsification rather than high temperature emulsification. It relates to atopic improvement lotion using the process.

Atopic dermatitis is an allergic disease that gets worse in dry climates due to genetic, environmental, and immunological causes. Also called atopic dermatitis.

The main symptoms of atopic dermatitis are severe itching, dry skin, rash, oozing, scab, and scaly skin. It can appear simultaneously with allergic rhinitis, asthma, allergic conjunctivitis, and atopic urticaria.

Due to genetic, environmental, and immunological causes, an abnormality has occurred in the stratum corneum, the outermost protective barrier of the skin. In addition, it seems that dry skin, infections caused by bacteria, viruses, and fungi, emotional factors, and environmental factors act in a complex way.

In particular, in the process of removing the causative agent that enters the human body with natural healing power, when the antibody (IgE) generated in the mast cell enters the substance (antigen) again, it causes a hypersensitivity reaction to form histamine, which is the cause of atopic dermatitis. is the main cause Histamine released from mast cells exhibits vasodilation, bronchial smooth muscle contraction, glandular cell secretion, and hyperstimulation, causing inflammatory and immediate allergic reactions, and mediating various biological effects such as mucus secretion and local protein secretion.

Therefore, as an external preparation for atopic dermatitis, a drug formulated with an antibacterial agent to remove harmful apoptosis-causing bacteria and the like has been used.

However, antihistamines, steroids, etc. are currently used as pharmaceutical therapies for atopic dermatitis, but steroids that are mainly used cannot be effective without long-term administration, and have local and systemic side effects, which is a clinical problem. . It has been reported that long-term use of steroid hormones thins the skin layer, induces osteoporosis, or inhibits growth in children. Therefore, there is a need for development of an agent for improving atopic skin disease that has no side effects and has excellent efficacy. There is an urgent need for the development of a natural atopic improving agent rather than a harmful ingredient like steroids. In particular, using room temperature emulsification rather than high temperature emulsification, there is a further need for an improving agent that can effectively treat atopy without destruction of components useful for the treatment of atopy.

Korean Patent Registration No. 10-1705482 (Registered on February 03, 2017) Korea Patent Publication No. 10-2018-0125354 (published on November 23, 2018) Korean Patent Registration No. 10-1774788 (registered on August 30, 2017) Korean Patent Publication No. 10-2011-0011241 (published on February 08, 2011)

It is an object of the present invention to provide a lotion for improving atopic dermatitis using a room temperature emulsification process that helps to efficiently treat atopy without destruction of components useful for atopy treatment using room temperature emulsification.

According to the present invention for solving the above invention, in the lotion manufactured using the room temperature emulsification process method, there is provided an atopic improvement lotion using the room temperature emulsification process formed by mixing an emulsifier and a thickener.

The emulsifier is composed of polyglyceryl-4 caprate, polyglyceryl-3 ricinoleate, and the thickener is characterized in that it is composed of ammonium acryloyldimethyltaurate/vpicopolymer.

The emulsifier is contained in an amount of 0.2 to 30% by weight, and the thickener is included in an amount of 0.01 to 15% by weight.

The emulsifier is composed of 0.1 to 15% by weight of polyglyceryl-4 caprate and 0.1 to 15% by weight of polyglyceryl-3 ricinoleate, and the thickener is ammonium acryloyldimethyltaurate/vpicopolymer 0.01 It is characterized in that it is composed of ~15% by weight.

It is characterized in that the emulsification temperature of the room temperature emulsification process is 20 ~ 40 ℃.

In addition to the purified water, the ammonium acryloyldimethyltaurate/vpicopolymer, the polyglyceryl-4 caprate, and the polyglyceryl-3 ricinoleate, evening primrose extract, self-inflicted extract and evening primrose oil and Self-inflicted oil; characterized in that it is formed by further mixing.

The purified water 3-75% by weight, ammonium acryloyldimethyltaurate/V-copolymer 0.01-15% by weight, self-inflicted extract 0.01-35% by weight, evening primrose extract 0.01-50% by weight, evening primrose oil 0.01-40% by weight, It is characterized in that it is formed by mixing 0.01 to 40% by weight of self-made oil, 0.01 to 15% by weight of polyglyceryl-4 caprate, and 0.1 to 15% by weight of polyglyceryl-3 ricinoleate.

Allantoin in addition to the purified water, the ammonium acryloyl dimethyl taurate / VPicopolymer, polyglyceryl-4 caprate, polyglyceryl-3 ricinoleate, evening primrose extract, evening primrose oil, self-inflicted extract, self-inflicted oil, It is formed by further mixing Glycerin, Butylene Glycol, Beta-Glucan, Glyceryl Glucoside, 4-t-Butylcyclohexanol, Aphanothece Sacrum Exopolysaccharides, and 1,2-Hexanediol.

Allantoin 0.01-5 wt%, Glycerin 0.01-10 wt%, Butylene Glycol 0.01-10 wt%, Beta-Glucan 0.01-10 wt%, Glyceryl Glucoside 0.01-10 wt%, 4-t-Butylcyclohexanol 0.01-10 wt% , Aphanothece Sacrum Exopolysaccharides 0.001 to 5 wt%; characterized in that it is formed by mixing.

The self-inflicted oil is characterized in that it is formed by mixing 5 to 15% by weight of Jichipur oil and 85 to 95% by weight of olive oil.

A formulation was developed as an emulsifier combining 0.7 wt% of the Ammonium acryloyldimethyltaurate/VP copolymer, a thickener combining 0.7 wt%, HLB 14.5 hydrophilic emulsifier Polyglyceryl-4 Caprate 1.15 wt%, and HLB 2.3 lipophilic emulsifier Polyglyceryl-3 Ricinoleate 1.85 wt% characterized by one.

The content used is calculated using the HLB values of the hydrophilic emulsifier Polyglyceryl-4 Caprate (Emul01) and the lipophilic emulsifier Polyglyceryl-3 Ricinoleate (Emul02), and the content calculation formula is "HLB (vegetable oil) - HLB (Emul02) / HLB (Emul01) ) - HLB (Emul02)" is characterized.

The present invention is purified water; Ammonium acryloyldimethyltaurate/vpicopolymer as thickener; polyglyceryl-4 caprate, polyglyceryl-3 ricinoleate as emulsifiers; Evening primrose extract; self-inflicted extract; Evening primrose oil; It provides a lotion for improving atopic dermatitis through a room temperature emulsification process formed by mixing self-inflicted oil.

The atopic improvement lotion through the room temperature emulsification process provided by the present invention is formed by further mixing Allantoin, Glycerin, Butylene Glycol, Beta-Glucan, Glyceryl Glucoside, 4-t-Butylcyclohexanol, Aphanothece Sacrum Exopolysaccharides, and 1,2-Hexanediol.

In addition, according to the present invention, dispersing and dissolving a water-soluble component in purified water to prepare an aqueous phase; preparing an oil phase by dissolving an oil-soluble component in an emulsifier at room temperature; There is provided a method for improving atopic dermatitis using a room temperature emulsification process comprising; preparing a lotion by adding an oil phase part while stirring the aqueous phase part.

An oil phase is prepared by dissolving the oil-soluble component in 0.1 to 30% by weight of the emulsifier at room temperature, and the oil phase is added at 20 to 40° C. while stirring the aqueous phase to prepare a lotion.

Atopic improvement lotion using room temperature emulsification process according to the present invention adopts ammonium acryloyldimethyl taurate / VPicopolymer as a thickener, and as an emulsifier, polyglyceryl-4 caprate, polyglyceryl-3 ricinoli By adopting 8, the lotion is provided through an emulsification process at room temperature, and the present invention can sufficiently satisfy the conditions that the thickener dissolves well at room temperature, the emulsifier must be liquid at room temperature, and the final emulsification state is thermodynamically stable.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The objects, features and advantages of the present invention will be more readily understood by referring to the accompanying drawings and the following detailed description. In addition, in describing the present invention, if it is determined that a detailed description of a related known configuration or function may obscure the gist of the present invention, the detailed description thereof will be omitted.

Evening primrose and self-inflicted herbs are natural products with ingredients that inhibit the activity of mast cells, the main cause of atopic dermatitis. Evening primrose and self-inflicted herbs are effective in inflammatory lesions such as atopic dermatitis, and contain ingredients such as linoleic acid and gamma linoleic acid, which are effective in antioxidants. This has been confirmed through animal model tests using evening primrose, inhibition of IgE production using self-inflicted plants, mast cell degranulation inhibition, and clinical tests (Han SH, Heo MH, Park JH, Lee YJ, Park MK. Aromatherapy. Hyunmoonsa, Seoul, p123, 2002.), (Seon Ju Kim, Effects of Evening Primrose Oil and Evening Primrose-rosemary Mixed Oil on Atopic Dermatitis-induced Animal Model, Asian J Beauty Cosmetol 2017; 15(4): 399-410), (Suyong Kim ( 2006) Effect of self-inflicted mast cells on allergic inflammatory response of mast cells, Kyung Hee University Graduate School of Oriental Medicine, Master's thesis), (Kim Joo-young (2006) The effects of gromwell (Lithospermm erythrorhizon Sieb. et Zucc.) for skin moisturizing and treatment of atopic dermatitis Kyung Hee University East-West Medical School, PhD thesis)

However, in the case of natural extraction raw materials, there is a possibility that the active ingredient is partially destroyed or deformed by exposure to high temperature. The cyconin component of self-inflicted plant is destroyed at 65℃ or higher, and vitamin C and minerals contained in natural products are also denatured when heated to 50~70℃ or higher.

In the case of lotion and cream cosmetics, they are emulsified through a high-temperature emulsification process, and in the case of natural extracts, the active ingredients are highly likely to be destroyed or deformed by exposure to high temperatures.

So, in most cases, after the high temperature emulsification process, the temperature of the bulk product is lowered by cooling, and then the natural extraction raw material is added. However, the amount of natural extraction raw materials that can be added while preserving the emulsion form is small, and in this case, it is difficult to sufficiently deliver the active ingredient to the skin.

If the high temperature emulsification process of the whole process is replaced with the room temperature emulsification process, a large amount of extraction raw materials can be added before the emulsification process to maximize the effect of the active ingredient.

Focusing on this, the present invention is atopy using a room temperature emulsification process developed for the purpose of maximizing the effect of active ingredients through a room temperature emulsification process without being destroyed by high temperature by adding a large amount of extraction raw materials (natural extracting raw materials) before the emulsification process. An improvement lotion may be provided.

Common emulsifiers (eg, glyceryl stearate, cetearyl alcohol, etc.) are solid and can be used only after heating to a high temperature. In addition, general thickeners (eg, carbomer, xanthan gum, etc.) are also not easily dissolved unless a high-temperature solvent is used.

O/W emulsions are thermodynamically unstable because the aqueous and oil phases are forcibly mixed, and as time goes by, they tend to return to a stable state. For stability of the formulation, emulsification is carried out at high energy, but if emulsification is carried out at room temperature, emulsification cracking may occur.

The case in which the structure of the emulsion dispersed in the continuous phase changes (when the emulsion cracking phenomenon occurs) is approximately as follows.

1) Breaking: Phase separation into two phases

2) Coalescence: Two droplets come together and become a larger volume of droplets.

3) Creaming: A concentrated phase is collected in a state where agglomeration is maintained due to the density difference between the two phases.

4) Flocculation: The process of maintaining the state of emulsified droplets but gathering them together

The present invention provides an atopic lotion that can properly improve atopic dermatitis without destroying the main active ingredient by finding an optimal ratio of thickener and emulsifier and stably emulsifying it even at room temperature.

The thickener and emulsifier candidate groups found in the present invention are as follows.

<Emulsifier>

Polyglyceryl-4 Caprate

Liquid, HLB 14.5 (hereinafter referred to as Emul01)

Polyglyceryl-3 Ricinoleate

Liquid, HLB 2.3 (hereinafter referred to as Emul02)

<Thickener>

Ammonium Acryloyldimethyl Taurate/Beheneth-25,

Methacrylate crosspolymer (hereinafter referred to as Tck01)

Dehydroxanthan Gum (hereinafter referred to as Tck02)

Ammonium acryloyldimethyltaurate/VP copolymer (hereinafter referred to as Tck03)

Acrylate Copolymer (hereinafter referred to as Tck04)

By using the emulsifier and thickener, a stable formulation is developed even at room temperature emulsification, and the stability of the formulation is confirmed through an accelerated test.

<Calculation of emulsifier content>

The amount used is calculated using the HLB values of the hydrophilic emulsifier Emul01 and the lipophilic emulsifier Emul02.

HLB(Emul02) = 2.3

HLB(Emul01) = 14.5

Vegetable oil HLB ≒ 7.0

HLB (vegetable oil) - HLB (Emul02) / HLB (Emul01) - HLB (Emul02) = 38.52%

Emul02 = 61.48%, Emul01 = 38.52%

When using 3% emulsifier, Emul02 = 1.84, Emul01 = 1.15

<Overall experimental method>

The present invention provides a lotion for improving atopic dermatitis using an emulsification process at room temperature. The atopic improvement lotion using the room temperature emulsification process of the present invention comprises the steps of preparing an aqueous phase by dispersing and dissolving a water-soluble component in purified water, dissolving an oil-soluble component in an emulsifier at room temperature to prepare an oil phase, and adding an oil phase while stirring the aqueous phase preparing a lotion.

(1) If there is no other indication after that, the experiment follows the following method.

① Disperse and dissolve the water-soluble component in purified water to prepare the aqueous phase. The water-soluble component may be glycerin, butylene glycol, vegetable extract, and the like. The aqueous phase contains thickener, allantoin, 1,3-BG, Glycerin, 1,2-Hexanediol. This is called phase A.

② The oily part is prepared by dissolving oil-soluble ingredients such as vegetable oil in an emulsifier at room temperature. The oil-soluble component may be olive oil, sunflower seed oil, mineral oil, etc. in addition to vegetable oil. This is called phase B.

③ While stirring the completely dissolved phase A of the aqueous phase, slowly add phase B, which is the oil phase, at 20 to 40 ℃ to emulsify at room temperature.

④ After confirming the properties, it is finished.

(2) The above experiment is an experiment in which a thickener and an emulsifier are combined at room temperature to increase the viscosity through cross-linking, and to further create a micellar structure by forcibly confining the aqueous and oil phases.

(3) When checking the properties, the formulation should be adjusted to a level similar to or better than the stability, sensory, and thickness of general lotion formulations.

<Emulsification experiment with different thickeners>

1. Experimental Objectives

In order to determine the thickener to be used for emulsification at room temperature in the present invention, repeated emulsification experiments are performed by changing the type and amount of the thickener. The thickeners used in this experiment are Tck01, Tck02, Tck03, and Tck04 (Ammonium Acryloyldimethyl Touate/Beheneth-25, Methacrylate Crosspolymer).

2. Experimental content (%)

As a result of visual evaluation of phase separation observation, flow chart, and fluidity in a transparent container after long-term preservation and accelerated testing for the stability of the formulation, in the case of Tck01, Experiments 3 to 5 were stable, and the viscosity and fluidity as a lotion were tested in Experiment 4 was appropriate. In the case of Tck02, Experiment 8 was stable, but it seems difficult to use alone because the surface of the emulsification is uneven visually. The pH of each sample was slightly acidic, ranging from 5.1 to 5.2. In the case of Tck03, Experiments 11 to 13 were stable, and Experiment 12 was appropriate for viscosity and fluidity as a lotion. Since Tck04 is a thickener that has to undergo a neutralization process unlike the thickener tested previously, a neutralization process is added to the method described in <General Experimental Method>. After dissolving L-Arginine in purified water and adding it separately, the emulsification process was followed, and Experiment 15 was appropriate for viscosity and fluidity as a lotion.

<Sensory evaluation by thickener>

1. Among the samples tested with each thickener, a sensory evaluation was performed using a sample suitable for the appropriate amount (visible evaluation) of the lotion.

Tck01: A181030-D1 (0.7%)

Tck02: A181026-D2 (0.8%)

Tck03: A181030-D2 (0.7%)

Tck04: A181031-D2 (7.0%)

When scoring, Tck03 and Tck01 scored the highest. Tck03 and Tck01 are Aristoflex series thickeners, and have excellent touch and appearance. In particular, it was confirmed that Tck03 dissolves well in low-temperature water. In the case of Tck01, it takes a long time to dissolve, so the score is high, but it is excluded because it is expected that difficulties will arise during the actual process. Tck04 was the most stable, but the thickening agent was found to be pushed out, confirming that it was not suitable for lotion.

The sensory evaluation of the sample processed with Tck03 (Ammonium acryloydimethyltaurate/VP copolymer) was very good compared to other thickeners, so it was decided to test using Tck03 alone.

<Formulation Selection>

Finally, the formulation was formulated with a thickener combining Tck03 (0.7%), which received excellent evaluation in the sensory evaluation, and an emulsifier combining the hydrophilic emulsifier Emul01 (1.15%) with HLB 14.5 and the lipophilic emulsifier Emul02 (1.85%) with HLB 2.3. developed.

The content (%) of each component is shown in the table below.

DI-Water 78.5 Dissolution complete dissolution
Confirm oil paint Tck03 0.7 Allantoin 0.1 Tck03
complete dissolution
after confirmation
adding Glycerin 3 1,3-BG 2 Sunflower Oil 12 oil tank
separately
Dissolution complete dissolution
Confirm Emul01 1.15 Emul02 1.85 1,2-Hexanediol 0.7 Addition after emulsification
After confirmation of complete dissolution
End of process

For the atopic improvement lotion using the room temperature emulsification process of the present invention, hydrophilic emulsifier Emul01 and lipophilic emulsifier Emul02 were adopted as emulsifiers through the above experiments, and Tck03 ammonium acryloyldimethyl taurate / Vpicopolymer ( Ammonium Acryloyldimethyltaurate/VP Copolymer) was adopted. Atopic improvement lotion using the room temperature emulsification process of the present invention based on the emulsifier and thickener is purified water, Emul01, Emul02, Tck03, Allantoin, Glycerin, Butylene Glycol, Beta-Glucan, Glyceryl Glucoside, 4-t-Butylcyclohexanol, Aphanothece It is formed by mixing Sacrum Exopolysaccharides, 1,2-Hexanediol.

In the present invention, purified water, ammonium acryloyldimethyltaurate / Vpicopolymer as a thickener, polyglyceryl-4 caprate, polyglyceryl-3 ricinoleate as an emulsifier, evening primrose extract, self-inflicted extract, evening primrose oil, self-inflicted Provides atopic improvement lotion through an emulsification process at room temperature formed by mixing oil.

In the present invention, purified water 3-75% by weight, evening primrose extract 0.01-50% by weight, self-inflicted extract 0.01-50% by weight, evening primrose oil 0.01-40% by weight, self-inflicted oil 0.01-40% by weight, Emul01 0.01-15% by weight, Emul02 There is provided an atopic improvement lotion using a room temperature emulsification process, characterized in that it is formed by mixing 0.01 to 18% by weight and 0.01 to 15% by weight of Tck03.

The atopic improvement lotion using the room temperature emulsification process of the present invention is specifically purified water 3 to 75% by weight, evening primrose extract 0.01 to 50% by weight, self-inflicted extract 0.01 to 50% by weight, evening primrose oil 0.01 to 40% by weight, self-inflicted oil 0.01 to 40 wt%, Emul01 0.01~15 wt%, Emul02 0.01~18 wt%, Tck03 0.01~15 wt%, Allantoin 0.01~5 wt%, Glycerin 0.01~10 wt%, Butylene Glycol 0.01~10 wt%, Beta-Glucan 0.01 ~10 wt%, Glyceryl Glucoside 0.01-10 wt%, 4-t-Butylcyclohexanol 0.01-10 wt%, Aphanothece Sacrum Exopolysaccharides 0.001-5 wt%, Symsitive 1609 0.1 wt%, SDH62a (1,2-Hexanediol) 0.5 wt% , Sacran B 0.03% by weight, S190087 0.015% by weight.

<Evening primrose and dwarf root (self-made)>

Compared to the increasing incidence of atopic dermatitis, the detailed mechanism of action for atopic dermatitis and the development of effective drugs for treatment are still insufficient. However, as reactive oxygen species has been identified as one of the lesion factors, a therapeutic approach is being attempted in terms of antioxidants. (Huh EJ al, Increased reactive oxygen species production by peripheral blood mononuclear leukocytes, not by polymorphonuclear leukocytes, in atopic dermatitis. Allergy Asthma & Respiratory Diseases, 14: 53-61, 2004.)

In the present invention, a lotion was prepared through an emulsification process at room temperature using two types of vegetable extracts and vegetable oil as main components, evening primrose and chives root. Evening primrose and borage root are representative botanical ingredients known to have good effects on inflammatory lesions such as atopic dermatitis.

The following is a summary of research and test data on the efficacy of evening primrose and sage root.

<Evening Primrose>

Evening primrose is known to be effective against inflammatory lesions such as atopic dermatitis. (Battaglia S. The complete guide to aromatherapy (2nd edition). Perfect Potion, Zillmere, p342, 2004.)

In particular, it contains ingredients such as palmitic acid, stearic acid, gamma linolenic acid, and oleic acid, including linoleic acid, which are good for antioxidant, and is known to have antioxidant, antibacterial and anti-allergic effects. (Han SH, Heo MH, Park JH , Lee YJ, Park MK. Aromatherapy. Hyunmoonsa, Seoul, p123, 2002.)

In order to confirm this effect, the data on the animal test for atopic dermatitis conducted using oil extracted from evening primrose as a material is summarized below.

(1) Evening Primrose Oil and Atopic Dermatitis Animal Model (Seon Ju Kim, Effects of Evening Primrose Oil and Evening Primrose-rosemary Mixed Oil on Atopic Dermatitis-induced Animal Model, Asian J Beauty Cosmetol 2017; 15(4): 399-410 )

Next, using evening primrose oil (evening primrose seed oil), the body weight and organ weight change, sensory evaluation, and antioxidant effect were analyzed for NC/Nga mice, a model of atopic dermatitis, and the measurement of IgE, an immune index, and mast cells from mouse tissues. It is a data that explores the possibility of application as a therapeutic substitute for atopic dermatitis by studying the degranulation and changes in the skin barrier. From the bottom, the oil extracted from evening primrose is labeled E oil.

As a result of sensory evaluation, among a total of 15 points, the atopic dermatitis induced group was 13ㅁ1.62 and the E oil treated group was 4ㅁ0.71, showing a significant difference compared to the AD induced group (p <0.01), consistent with the photo results of animal experiments. could see that

As a result of checking the EDA of the ethanol sample containing 20, 50, and 80 μL of E oil, the EDA of E oil was 15.8% by weight (p <0.05), 36.7% by weight (p <0.01), and 52.4% by weight (p <0.001), respectively. ) showed a significant increase compared to the control group.

As a result of measuring LPA, E oil was 21.4 wt% (p <0.05), 42.5 wt% (p <0.01), and 63.2 wt% (p <0.001), respectively, indicating a significant increase compared to the control group. Considering the results of the study that atopic dermatitis lesions and oxidative damage are closely related, in the sensory evaluation of this study, E oil showed high antioxidant activity, suggesting that it has therapeutic efficacy for atopic dermatitis.

The epidermal thickness was 614.3% by weight (109.71ㅁ11.85) in the AD induced group compared to 100.0% by weight (17.86ㅁ1.32) in the control group, and 314.5% by weight (56.17ㅁ8.23; p <0.01) when treated with E oil. It showed a significant decrease compared to the control group. Epidermal thickness increase is a phenomenon caused by lesions such as atopic dermatitis or oxidative damage, cytokines such as IFNγ and TNFα, or thickening or inflammation of the dermal layer of the skin. It is known that the production of ROS by overactivation of -methyl-D-aspartate (NMDA) receptors and metabolic processes for homeostasis restoration following skin damage progress, causing active epidermal proliferation and thickening of the skin barrier (Kim). HJ al. Atopic dermatitis and skin barrier dysfunction. Allergy Asthma & Respiratory Disease, 1:20-28, 2013.)

In the results of this study, the epidermal thickness in the AD-induced group was significantly increased compared to the control group, and in the case of E oil treatment, the epidermal thickness was significantly decreased compared to the atopic dermatitis-inducing group.

In the quantitative measurement of IgE, the atopic dermatitis-inducing group increased significantly to 152.8 wt% (0.081w0.009) compared to 100.0 wt% (0.053w0.007) of the control group, and 141.5 wt% (0.075w0.004; p <0.05) in E oil treatment. ), indicating a significant decrease.

The number of degranulation of mast cells was 1.4 wt% (w0.3) in the control group, and was very high at 28.6 wt% (w5.6) in the atopic dermatitis-induced group. In contrast, in the E oil treatment group, 10.9% by weight (ㅁ1.4; p<0.01) showed a significant decrease.

<Chichi root (self-inflicted)>

In oriental medicine, self-inflicted herb has been widely used for the treatment of skin-related diseases. Recently, as interest in the anti-inflammatory and skin diseases of self-inflicted herb has increased, the immune system is involved in acute inflammation, various allergic inflammatory reactions, and atopic dermatitis. Research on the efficacy of extracts of self-inflicted herbs and shikonin, an indicator component, related to the regulation and inhibition of mediator histamine, IgE, TNF-α, cytokines, chemokine receptor, NF-κB, iNOS, etc. (Ji) Hoon Ju al, Progress on Phytochemical and Atopic Dermatitis-related Study of the Root of Lithospermum erythrorhizon, Kor. J. Pharmacogn. 41(2):74~88(2010))

(1) Suppression of self-inflicted extract and IgE production and inhibition of mast cell degranulation

Serum IgE level is increased in more than 80% by weight of atopic dermatitis patients, and this level is generally reported to be proportional to the clinical severity of atopic dermatitis. Therefore, it can be seen that the inhibitory effect of the B cell action that produces IgE has an important meaning in the treatment of atopic dermatitis.

It has been reported that the water extract of self-inflicted water has the effect of inhibiting the expression of anti-CD40 and rIL-4 induced cytokine genes and the generation of IgE in B cells of mice. The self-inflicted water extract at a concentration of 100 μg/ml exhibited an effect of inhibiting the production of IgE (27.4% by weight) compared to the control (45.5% by weight production). In addition, the cytokines IL-1β, IL-4, IL-5, IL-6 and TNF-α showed the effect of significantly inhibiting the gene expression, but showed the effect of significantly increasing the production of IFN-γ. Since the increase in IFN-γ is known to inhibit the action of Th2, mast cells bind IgE and release various chemical transmitters during the acute phase and the onset of atopic dermatitis. These chemical transmitters induce various allergic inflammatory reactions cause to In order to investigate the mechanism of action of self-inflicted antiallergic effect, a study result using rat mast cells and human mast cells (HMC-1) has been reported. Effect on inflammatory response, Department of Oriental Medicine, Graduate School of Kyung Hee University, Master's thesis.) After pre-treatment with water extract of self-inflicted water on rat mast cells, degranulation was induced with compound 48/80. As a result, concentration-dependent degranulation at concentrations above 0.1 mg/ml showed an inhibitory effect, and at a concentration of 5 mg/ml, it showed an inhibitory effect of 90% by weight. The water extract of Own root also inhibited histamine secretion in a concentration-dependent manner at a concentration of 0.1 mg/ml or more, and showed an inhibitory effect of 92% by weight at a concentration of 1 mg/ml. For HMC-1, after inducing inflammation with phorbol 12-myristate 13-acetate (PMA) and A23187, the effect of significantly inhibiting the secretion of IL-6, IL-8, and TNF-α was reported. When the concentration of the self-inflicted extract was 0.1, 1, and 5 mg/ml, the production of IL 6 was inhibited in a concentration-dependent manner (68.2% by weight was inhibited at 5 mg/ml), and the production of TNF-α was also inhibited in a concentration-dependent manner. (77.3 wt% inhibition at 5 mg/ml). Based on the results of this study, it was considered that the self-inflicted extract blocks the inflammatory allergic reaction of mast cells through the mechanism of inhibiting the activation of NF-κB by inhibiting the secretion of histamine and the degradation of IκB-α.

(2) Prevention of cell death by self-inflicted extract and UV rays

Although UV rays are not directly related to atopic dermatitis, they are one of the biggest environmental factors that damage the skin. In particular, UVB, which has a short wavelength, causes erythema or inflammation on the skin when exposed for a long time, and in severe cases can also cause skin cancer.

Ishida et al. (contains 4.4 wt% of shikonin, 34.4 wt% of acetylshikonin, and 20.7 wt% of isobutylshikonin among the total shikonin derivatives) of self-inflicted ether extract (NHEK) pretreated with UVB irradiation. At -7.5 μg/ml concentration, the survival rate of NHEK was increased by 15-30% by weight compared to the control, and the pro-inflammatory cytokines IL-1α, IL-1ㅯ, IL-6, IL-8 even in NHEK damaged by UVB. and significantly inhibited the production of TNF-α. In addition, it was reported that the self-inflicted extract inhibits the production of p53 protein and serine 15 phosphorylated p53, and prevents UVB-induced cell apoptosis by inhibiting the activity of caspase-3 (Ishida, T. and Sakaguchi, I. (2007)). Protection of human keratinocytes from UVB-induced inflammation using root extract of Lithospermm erythrorhizon. Biol. Pharm. Bull. 30: 928-934.)

In an experiment on a series of skin inflammatory diseases caused by damage to sunlight (UVB), after UVB (800mJ/cm2) was irradiated to male C57BL mice, transepidermal water loss (TEWL), superoxide dismutase A study on changes in the expression of (SOD) and catalase (CAT) and skin regeneration has been reported.

In this study, after applying the emulsion containing 0.5% by weight of water extract of self-inflicted root to each measurement target, the time period and the values that showed the greatest effect for a total of 160 hours were examined. As a result, in terms of osmotic water loss, It showed a reduction effect of about 32% by weight compared to the control group. In the erytherma index, there was a sedative effect of about 23% by weight compared to the control group at 24 hours. The activity of SOD was observed to have a decreasing effect of about 21% by weight compared to the control at the 120 time period, but the measurement of CAT was observed to have an increasing effect of about 167% by weight compared to the control at the 48 time period. As a result of observation with an optical microscope and a scanning microscope, it was reported that the skin level of the control group was recovered almost 160 hours after the injection of the self-inflicted extract.

(3) Shikonin and Microglial cells of own origin

Although microglial cells play an important role in the immune and inflammatory responses of the central nervous system, chronic activation of microglial cells in pathological conditions is known to cause fatal damage to the central nervous system. It has been reported that shikonin and its derivatives, the main component of self-inflicted substances, can help protect the central nervous system from nerve damage by inhibiting the activation of these microglial cells.

Nam et al. showed that iNOS, IL-1β, TNF-α and COX- induced by LPS (100 ng/ml) after pretreatment of microglial cells with isobutyrylshikonin (5) and isovalerylshikonin (8) at a concentration of 4 μM for 30 min. 2 It was reported that the expression of mRNA and the production of PGE2 were significantly inhibited. Shikonin derivatives also significantly inhibited Akt phoshorylation and NF-κB activation. Therefore, the authors predicted that the main mechanism by which shikonin derivatives perform anti-inflammatory action on microglial cells would be the process of inhibiting the Akt signaling pathway that activates NF-κB by IκB-α degradation (Nam, KN, Son, MS). , Park, JH and Lee, EH (2008) Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-κB: neuroprotective implications. Neuropharmacology 55: 819-825.)

(4) Clinical trial case of self-inflicted extract

A clinical trial to investigate the efficacy of self-inflicted extract on atopic patients was conducted with Kyunghee University oriental medicine students and 149 outpatients at Kyunghee Medical Center (Kim Joo-young (2006) The effects of gromwell (Lithospermm erythrorhizon Sieb. et Zucc.) For skin moisturizing and treatment of atopic dermatitis. Kyung Hee University East-West Medical School, Ph.D.) 83 healthy general subjects (34 males, 49 females) were compared with 42 normal gromwell group (NG, self-inflicted group) and 41 normal subjects. It was divided into placebo group (NP), and among 66 atopic patients (28 males, 38 females), the self-inflicted extract (70 The results of body composition, blood analysis, skin hydration and skin ceramide content were collected while taking the drug in powder form for 10 weeks.

As a result of the clinical test, in terms of skin hydration, the NG group and AG group, which received dietary administration, showed an increase of 14.8% by weight and 17.3% by weight, respectively, from 0 to 10 weeks. Also in the concentration values of epidermal ceramide, the NG group and AG group showed a large increase of 100% by weight and 45% by weight, respectively. From this, it was shown that the self-indulgent extract had some effect on skin hydration and improvement of epidermal ceramide. Also, in the experiment investigating the change in IgE level after self-inflicted administration, the NG group in the healthy general subject group increased by 5.3% by weight, the NP group decreased by 0.7% by weight, and the NG group in the atopic patient group decreased by 12.3% by weight. , the NP group was increased by 22.3% by weight.

So far, it has been found that evening primrose and chives root, which are the main ingredients of this product, are effective in inflammatory lesions such as atopic dermatitis.

<Extract replacement experiment>

1. Evening primrose extract, self-inflicted extract, evening primrose oil, and self-inflicted oil, which are the extraction results, were prescribed by replacing the developed room temperature emulsifying formulation.

2. Experiment

<Quality Test>

When the sample to which Experiment 18 was applied was referred to as Sample A, and the existing lotion prescription sample was referred to as Sample B, a sensory evaluation test was conducted on nine adult males and females.

Sample A (A190219-D1)

Sample B (A190219-D3)

After using it for a week, it was evaluated for "appliedness/moisture feeling/oily feeling/stickiness/overall review/after use (compare A and B)/preferred sample when purchasing". The score was given on a scale of 1 to 5.

Based on the average opinion, the test facilitator wrote the results.

Sample A: No irritation, higher moisture content than Sample B

Less sticky, easy to use

It spreads smoothly and adheres well and helps dryness.

Moderately oily

I'm sorry about the viscosity.

Sample B: Non-irritating, non-sticky, soft

The spreadability, absorption time, oily feeling, and moisture retention period after application were insufficient compared to Sample A.

Sample A, to which the room temperature emulsification process was applied, obtained a higher evaluation than the existing lotion prescription sample B.

Tables 8 and 9 below are part of the PumPyeongji.

<Stability test>

go. long-term preservation test

(1) Test purpose

A long-term storage test is conducted to determine the stability of the new formulation of Atopanax (tentative name), which is the result of the task 'Lotion using room temperature emulsification process'.

When stored under appropriate conditions, confirm that it meets the functional, aesthetic, and physical and chemical quality standards.

Accordingly, the purpose is to set the expiration date and expiration date.

(2) Test target product

Atopanax test sample 5EA

Test No. : A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190326-N3

(3) Test equipment

Incubator (C-INA, Changshin Science)

thermometer

hygrometer

(4) Test methods and procedures

According to the cosmetic stability test guideline issued by the Food and Drug Administration, it is tested under the appropriate standards, test methods and test conditions according to the formulation.

Selection of lots: In the guideline, it is a rule to test for more than 3 lots, and the sample used in this experiment is suitable for 5 lots.

5 lots: A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190326-N3

Storage conditions: room temperature (temperature: 25±2℃ / relative humidity: 60±5%)

Test period: In principle, it is a rule to test for more than 6 months in the guideline, and in this experiment, it is assumed that the test is carried out from 2019.03.26 to 2019.09.26.

Measurement period: Test start (2019.03.26), 3 months later (2019.06.26), final (2019.09.26.)

Test items: properties, color, odor, feeling of use, viscosity, change in mass, degree of separation, emulsification state, pH

(5) Test results

(A) Test start (2019.03.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance lotion award lotion award lotion award lotion award lotion award colour pale pink pale pink pale pink pale pink pale pink dreadlocks no odor no odor no odor no odor no odor feeling Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Viscosity 96.4KU 96.5KU 99.7KU 93.0KU 98.8KU mass change 101.17g 101.24g 85.15g 99.33g 101.69g Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 6.65 6.74 6.52 6.80 6.66

(B) After 3 months (2019.06.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance lotion award lotion award lotion award lotion award lotion award colour pale pink pale pink pale pink pale pink pale pink dreadlocks no odor no odor no odor no odor no odor feeling Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Viscosity 102.8KU 102.2KU 106.6KU 101.5KU 103.0KU mass change 100.85g 101.02g 85.28g 99.52g 101.75g Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 6.38 6.51 6.40 6.39 6.19

(C) After 6 months (2019.09.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance lotion award lotion award lotion award lotion award lotion award colour pale pink pale pink pale pink pale pink pale pink dreadlocks no odor no odor no odor no odor no odor feeling There is no change in the properties, and it maintains a sense of tightness with the skin with moderate moisture and oiliness, and there is no stickiness. There is no change in the properties, and it maintains a sense of tightness with the skin with moderate moisture and oiliness, and there is no stickiness. There is no change in the properties, and it maintains a sense of tightness with the skin with moderate moisture and oiliness, and there is no stickiness. There is no change in the properties, and it maintains a sense of tightness with the skin with moderate moisture and oiliness, and there is no stickiness. There is no change in the properties, and it maintains a sense of tightness with the skin with moderate moisture and oiliness, and there is no stickiness. Viscosity 97.1KU 98.1KU 97.8KU 96.5KU 100.5KU mass change 100.29g 100.52g 84.88g 99.18g 101.26g Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 5.82 5.72 5.75 5.96 5.70

(6) Conclusion

A long-term storage test was conducted to determine the stability of the new formulation of Atopanax (tentative name), the result of 'lotion using room temperature emulsification process'.

This test was conducted for 6 months in accordance with the cosmetic stability test guidelines issued by the Food and Drug Administration under appropriate standards, test methods and test conditions.

It was stored at room temperature to proceed, and during the test, evaluation was carried out by testing the properties, color, odor, feeling of use, viscosity, mass change, separation, emulsification state, and pH.

As a result of the stability test, all 5 lots of samples (A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190325-N1) maintained the emulsified state without any change in properties, and the odor and separation were also excellent. There was a slight change in the mass, pH, and viscosity according to the change, but it did not deviate from the titration standard.

As for the feeling of use, it has an appropriate moisture and oily feeling, has a good skin-tasting feeling, and has a non-sticky feeling. As a result of this stability test, it was confirmed that the quality standards were met.

me. accelerated test

(1) Purpose of the test

An accelerated test is carried out to determine the stability of the new formulation of Atopanax (tentative name), the result of the task 'Lotion using room temperature emulsification process'.

When stored under accelerated conditions for a short period of time, confirm that it meets the functional, aesthetic, and physical and chemical quality standards.

Accordingly, the purpose is to set the expiration date and expiration date.

(2) Test target product

Atopanax test sample 5EA

Test No. : A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190326-N3

(3) Test equipment

Incubator (C-INA, Changshin Science)

thermometer

hygrometer

(4) Test methods and procedures

According to the cosmetic stability test guideline issued by the Food and Drug Administration, it is tested under the appropriate standards, test methods and test conditions according to the formulation.

Selection of lots: In the guideline, it is a rule to test more than 3 lots, and the sample used in this experiment is suitable for 5 lots.

5 lots: A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190326-N3

Storage conditions: high temperature (temperature: 40±2℃/relative humidity: 75±5%)

Test period: In principle, it is a rule to test for more than 6 months in the guideline, and in this experiment, it is supposed to be tested from 2019.03.26 to 2019.09.26.

Measurement period: Test start (2019.03.26), 3 months later (2019.06.26), final (2019.09.26.)

Test items: properties, color, odor, feeling of use, viscosity, change in mass, degree of separation, emulsification state, pH

(5) Test results

(A) Test start (2019.03.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance lotion award lotion award lotion award lotion award lotion award colour pale pink pale pink pale pink pale pink pale pink dreadlocks no odor no odor no odor no odor no odor feeling Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Viscosity 96.4KU 96.5KU 99.7KU 93.0KU 98.8KU mass change 101.17g 101.24g 85.15g 99.33g 101.69g Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 6.65 6.74 6.52 6.80 6.66

(B) After 3 months (2019.06.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance thin lotion thin lotion thin lotion thin lotion thin lotion colour apricot apricot apricot apricot apricot dreadlocks no odor no odor no odor no odor no odor feeling Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Adhesion and spreadability are suitable, and it has excellent moisturizing and oily feeling. not sticky Viscosity 70.7KU 70.3KU 70.7KU 71.0KU 75.2KU mass change 96.74g 94.42g 93.93g 91.53g 98.49g Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 5.49 5.40 5.29 5.33 5.28

(C) After 6 months (2019.09.26.)

A190318-D1 A190321-D1 A190321-S1 A190322-S1 A190326-N3 appearance thin lotion thin lotion thin lotion thin lotion thin lotion colour apricot apricot apricot apricot apricot dreadlocks no odor no odor no odor no odor no odor feeling It has a moderate oiliness and softness without any change in properties, good adhesion to the skin, and no stickiness. It has a moderate oiliness and softness without any change in properties, good adhesion to the skin, and no stickiness. It has a moderate oiliness and softness without any change in properties, good adhesion to the skin, and no stickiness. It has a moderate oiliness and softness without any change in properties, good adhesion to the skin, and no stickiness. It has a moderate oiliness and softness without any change in properties, good adhesion to the skin, and no stickiness. Viscosity 69.9KU 70.1KU 70.3KU 70.5KU 72.8KU mass change 94.27g 92.68g 90.24g 81.75g 95.94 Separation does not exist does not exist does not exist does not exist does not exist emulsified state excellent excellent excellent excellent excellent pH 4.96 4.95 4.88 5.10 4.90

(6) Conclusion

An accelerated test was conducted to determine the stability of the new formulation of Atopanax (tentative name), which is the result of 'lotion using room temperature emulsification process'.

This test was conducted for 6 months in accordance with the cosmetic stability test guideline issued by the Food and Drug Administration under suitable standards, test methods and test conditions.

It was stored under accelerated conditions for a short period of time and was evaluated by testing properties, color, odor, feeling, viscosity, mass change, separation, emulsification state, and pH.

As a result of the stability test, all 5 lots of samples (A190318-D1, A190321-D1, A190321-S1, A190322-S1, A190325-N1) all increased in viscosity according to temperature, but maintained the emulsified state without changing the overall properties and odor and separation It was also maintained excellently, and although there were some changes in the mass, pH, and viscosity according to the change of storage period, it did not deviate from the appropriate quality standards.

As for the feeling of use, it has appropriate moisture and oily feeling, has good adhesion to the skin, and maintains a non-sticky state. As a result of this stability test, it was confirmed that the quality standards were met.

<Human patch test>

go. safety test

(1) Overview

Primary irritation test by skin patch

Testing according to the Cosmetics Guidelines of the Ministry of Food and Drug Safety, the Declaration of Helsinki, and the OATC Skin Clinical Test Center Standard Operating Instructions (SOP)

Test date: 2019.03.27. ~ 2019.03.29.

Report date: 2019.04.10.

Test control number: OATC-190327-SVP-KR0001

(2) Test product

Ato Panax Lotion (190327-K-116)

Form: pink cream

Stored for 1 month after the end of the test, and the evaluation product given to the subject is collected after the end of the test and completely discarded without a storage period

(3) Subjects to be tested

Adult men and women aged 20 to 60 who meet the selection criteria and do not meet the exclusion criteria

Test participants: 32 (no dropout)

No change in incidence, severity, or specificity of adverse events

(4) Institutional Ethics Committee (IRB) Review

Regulations for human application testing: to be conducted ethically in accordance with the Declaration of Helsinki and the Act on Bioethics and Safety

IRB deliberation: 2019.03.20. The test was initially approved and the test was conducted, and after the test was completed without any special changes, the end of this human application test was reported to the IRB.

(5) Test method

Test location: constant temperature and humidity space of the skin clinical test center (indoor temperature 20~25℃, humidity 40~60%)

Patch site: A flat area on the subject's back, except for the spine, where there is no pigmentation or skin damage.

Test method: Wipe the subject's back with 70% ethanol and dry it, load 20ml of the test product into the IQ Chamber, fix it on the skin, and attach it for 24 hours.

Irritation determination: The evaluation was performed 30 minutes and 34 hours after patch removal by a dermatologist according to the determination criteria. Based on the Frosch & Kligman, CTFA guideline, the skin reactivity was read, and the skin irritation level of the test substance was classified by referring to the skin irritation index generated by applying the Draize method.

sign Grade Criteria + One Slight erythema, either spotty or diffuse ++ 2 Moderate uniform erythema +++ 3 Intense erythema with edema ++++ 4 Intense erythema with edema&vesicles

skin irritation index Irritation assessment 0.00 to 0.25 Non (non) irritant 0.26 to 1.00 mild irritant 1.01 to 2.50 Moderate irritation 2.51 to 4.00 strong irritant

(6) test results

Judgment result on skin patch: The test product 'Ato Panax Lotion' was applied for 24 hours, and after 30 minutes and 24 hours after the patch was removed, the visual evaluation by a dermatologist showed that it was non-irritating.

Adverse reaction evaluation: As a result of physical examination by a dermatologist, no specific skin adverse reactions were observed during the test period.

(6) Conclusion

In this human application test, the primary stimulation test by skin patch of 'Ato Panax Lotion' was conducted on 32 adult males and females aged 20 to 60 years. The test product was applied for 24 hours, and as a result of evaluation 30 minutes and 24 hours after the patch was removed, it was judged as non-irritating.

<Human Applied Test>

Using the lotion formed by mixing the room temperature emulsification process of the present invention and evening primrose/self-inflicted extract and evening primrose/self-inflicted oil, the moisturizing effect and safety evaluation on atopic skin was conducted at the Clinical Trial Center of Daejeon University Dunsan Oriental Medicine Hospital.

Among adult men and women aged 12 to 45 years, who were diagnosed with atopic dermatitis according to the Hanifin-Rajka criteria and complained of mild atopic dermatitis with an EASI SCORE score of less than 6, after 4 weeks of application of Ato Panax lotion to the affected area, the skin moisture content By evaluating the amount of change and safety to prove the moisturizing effect before and after application, the moisturizing effect of Ato Panax lotion on atopic skin was confirmed. The subjects of analysis are 20, and the criteria for selecting subjects are as follows.

1. Men and women from 12 to 45 years of age

2. Those diagnosed with atopic dermatitis according to the Hanifin & Rajka diagnostic criteria

3. Moderate evaluation method for atopic dermatitis: Patients evaluated as mild with an EASI score of less than 6

4. Applicants who voluntarily sign the test consent form after being fully explained about the purpose and content of the test (however, in the case of a minor, consent from one guardian is required)

The criteria for exclusion of test subjects are as follows.

1. Pregnant or lactating women and women of childbearing potential

2. Persons who have been using skin external agents containing steroids for more than 1 month for the treatment of skin diseases

3. Those who have not passed 6 months after participating in the human body application test for moisturizing atopic skin

4. People with sensitive, hypersensitive skin

5. Those with skin abnormalities such as spots, acne, erythema, and capillary dilatation at the test site

6. Persons who have undergone treatment in the test site within 6 months before the start of the study

7. Persons who have used moisturizing or similar efficacy cosmetics and pharmaceuticals on the test site within 3 months before the start of the study

8. People with chronic wasting diseases (hyperthyroidism and hypothyroidism, asthma, diabetes, high blood pressure, etc.)

9. Patients with hepatic and renal impairment (ALT, AST, ALP ≥ double the upper limit of normal at screening or creatinine > 2.0 mg/dL)

10. People with irritation or allergy to cosmetics or medicines

11. Others who are considered unsuitable for the test in the judgment of the principal investigator

The test method is as follows.

Among the subjects diagnosed with atopic dermatitis, the test cream and the control cream were randomly assigned in the same ratio to mild EASI Score less than 6, and twice a day (morning and evening) the test site (of the atopic areas, the vertebrae and the nape of the neck). Apply to the desired area, including

Safety is evaluated by evaluating the degree of moisture content using a corneometer and safety evaluation before the start of application and 2 weeks and 4 weeks after application. As other observation items, the quality of life improvement effect was evaluated using the EASI score and skindex-29 Korean version.

The measurement site is carried out in one place on the anterior fossa and the nape of the neck with atopic dermatitis. After washing the test site with lukewarm water, let it rest in a constant temperature and humidity room (temperature: 22°±1°C, humidity: 45±5%) for 30 minutes, and then measure the skin moisture state.

For random assignment, SAS　 Analytics Pro (SAS Institute, Inc., Cary, North Carolina, USA) was used, and the assignment ratio was 1:1, and 50 subjects were assigned to each group considering the dropout rate.

Analysis

In this test, the efficacy and safety of the test product for moisturizing atopic skin were evaluated for men and women between the ages of 12 and 45 who were diagnosed with atopic dermatitis by the researcher.

1) The selected subjects did not have any special skin symptoms other than atopic dermatitis, and had no disease or drug history that could affect the test.

2) As a result of checking the skin surface moisture content, the interim results of 20 people in the test product group decreased after 2 weeks and 4 weeks of use, and showed statistical significance.

3) As a result of clinical examination and physical examination by a dermatologist for safety evaluation, there were no reports of any specific adverse reactions.

As a result of the interim analysis, it was found that the skin surface moisture content was significantly improved after using the product for 4 weeks compared to before use, and no side effects were particularly reported due to the use of the test product. As a result of the interim analysis of this test product, it is judged that there is an improvement effect on the skin barrier, and the result that can be safely used for subjects with mild atopic dermatitis is estimated.

<Analysis subject information>

For the analysis of subjects who participated in this study, 20 subjects in the test group were analyzed.

Compliance with product use was calculated as a percentage of the number of times used to the number of times used during the test period. The overall compliance of the 20 subjects who completed the trial was 95.86% on average, with the highest compliance being 100.00% and the lowest compliance being 90.65%.

[Result of skin surface moisture content (corneometer) measurement]

* Statistical analysis method: 1) Wilcoxon signed-rank test for categorical data (adverse reactions), and paired t-test for continuous data (water content, moisture loss) was used.

2) Efficacy evaluation was performed by ITT (Intent-To-Treat) analysis and PP (Per protocol) analysis.

As a result of confirming the skin surface moisture content, it was significantly increased for 4 weeks of use compared to before use.

[Safety evaluation result]

Safety evaluation was conducted by recording side effects, vital signs, and clinical pathology test results for the site where the test product was used. All test subjects who applied the test product for human application more than once were evaluated as the target for personality evaluation. The frequency of adverse events related to the test product and adverse events not associated with the test product was recorded. In principle, the evaluation of the degree of adverse reaction should be evaluated in stages according to the severity of symptoms by the person in charge of the test referring to the evaluation criteria. The causal relationship with the test product was evaluated by the person in charge of the test by classifying it into 6 stages according to the evaluation criteria.

As a result of the evaluation, there were no serious adverse events or abnormalities in clinical values.

[Evaluation variable value by visit for interim analysis]

(transdermal moisture loss (TEWL, g/m2/h), skin moisture content (Corneometer, AU)

The atopic improvement lotion using the room temperature emulsification process of the present invention is purified water 15 to 85% by weight, evening primrose extract 0.01 to 50% by weight, self-inflicted extract 0.01 to 50% by weight, evening primrose oil 0.01 to 40% by weight, self-inflicted oil 0.01 to 40% by weight , Emul01 0.01~15 wt%, Emul02 0.01~18 wt%, Tck03 0.01~15 wt%, Allantoin 0.01~5 wt%, Glycerin 0.01~10 wt%, Butylene Glycol 0.01~10 wt%, Beta-Glucan 0.01~10 It is formed by mixing 0.01 to 10% by weight of Glyceryl Glucoside, 0.01 to 10% by weight of 4-t-Butylcyclohexanol, and 0.001 to 5% by weight of Aphanothece Sacrum Exopolysaccharides.

The Tck03 ammonium acryloyldimethyl taurate/vpicopolymer. It is a thickener which is the main component of the present invention.

The Emul01 and Emul02 are emulsifiers which are the main components of the present invention.

1,3-B.G is butylene glycol.

The lotion of the present invention is valuable as an improving agent capable of effectively treating atopy without destruction of components useful for atopy treatment using room temperature emulsification rather than high temperature emulsification.

In the present invention, ammonium acryloyl dimethyl taurate / Vpicopolymer is adopted as a thickener, and polyglyceryl-4 caprate and polyglyceryl-3 ricinoleate are adopted as emulsifiers, and It is important to provide the lotion.

Since general thickeners and emulsifiers cannot be used, in order to make cosmetics through the room temperature emulsification process, the thickener dissolves well at room temperature, the emulsifier must also be liquid, and the final emulsification state must be thermodynamically stable.

However, in the case of the present invention, ammonium acryloyldimethyltaurate / Vpicopolymer is adopted, and polyglyceryl-4 caprate and polyglyceryl-3 ricinoleate are adopted as emulsifiers, so that the lotion is subjected to an emulsification process at room temperature. In this invention, the thickener as described above dissolves well even at room temperature, the emulsifier must also be in a liquid state, and the final emulsified state can sufficiently satisfy the thermodynamically stable condition. The main ingredients of the lotion of the present invention are ammonium acryloyldimethyltaurate/vpicopolymer as a thickener, polyglyceryl-4 caprate as an emulsifier, polyglyceryl-3 ricinoleate, evening primrose extract, evening primrose oil, self-inflicted ( Chichi root) extract, self-inflicted oil. In the present invention, it is possible to maximize the effect of the active ingredient through the emulsification process at room temperature without being destroyed by high temperature by adding a large amount of extraction raw materials before the emulsification process.

Terms such as "include", "comprise" or "have" described above mean that the corresponding component may be inherent unless otherwise stated, so it does not exclude other components. It should be construed as being able to further include other components. All terms, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs, unless otherwise defined. Terms commonly used, such as those defined in the dictionary, should be interpreted as being consistent with the meaning of the context of the related art, and shall not be interpreted in an excessive or excessively formal meaning unless explicitly defined in the present invention.

The above description is merely illustrative of the technical spirit of the present invention, and various modifications and variations will be possible without departing from the essential characteristics of the present invention by those skilled in the art to which the present invention pertains. Accordingly, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to explain, and the scope of the technical spirit of the present invention is not limited by these embodiments. The protection scope of the present invention should be construed by the following claims, and all technical ideas within the scope equivalent thereto should be construed as being included in the scope of the present invention.

Therefore, since the embodiments described above are provided to fully inform those of ordinary skill in the art to which the present invention belongs the scope of the invention, it should be understood that they are exemplary in all respects and not limiting, The invention is only defined by the scope of the claims.

Claims (12)

As an atopic improvement lotion prepared using a room temperature emulsification process,
It is formed by mixing an emulsifier, a thickener, atopic improvement ingredient and other additives,
About all ingredients of atopic improvement lotion
3 to 75% by weight of purified water;
0.2 to 30% by weight of an emulsifier composed of 0.1 to 15% by weight of Polyglyceryl-4 Caprate having HLB 14.5 as a hydrophilic emulsifier, and 0.1 to 15% by weight of Polyglyceryl-3 Ricinoleate having HLB 2.3 as a lipophilic emulsifier;
0.01-15 wt% of Ammonium acryloyldimethyltaurate/VP copolymer as a thickener;
As atopic improvement components, 0.01 to 35% by weight of self-inflicted extract, 0.01 to 50% by weight of evening primrose extract, 0.01 to 40% by weight of evening primrose oil, 0.01 to 40% by weight of self-inflicted oil;
Other additives: Allantoin 0.01~5% by weight, Glycerin 0.01~10% by weight, Butylene Glycol 0.01~10% by weight, Beta-Glucan 0.01~10% by weight, Glyceryl Glucoside 0.01~10% by weight, 4-t-Butylcyclohexanol 0.01~10 % by weight, Aphanothece Sacrum Exopolysaccharides 0.001 to 5% by weight, 1,2-Hexanediol 0.5% by weight;
is formed by mixing
Atopic improvement lotion using the room temperature emulsification process, characterized in that the room temperature emulsification process is made at a temperature of 20 ~ 40 ℃.
delete delete delete delete delete delete delete delete According to claim 1,
The self-inflicted oil is atopic improvement lotion using a room temperature emulsification process, characterized in that it is formed by mixing 5 to 15% by weight of Jichipur oil and 85 to 95% by weight of olive oil.
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