KR20040026268A - Topical composition for lowering pruritus or damaged skin barrier caused by atopic dermatitis - Google Patents

Abstract

By using an external skin composition of a liposome formulation selected from the group consisting of an itch relieving agent, an anti-inflammatory agent, a moisturizing agent, a skin barrier analog, and a skin protecting agent, it is possible to obtain an excellent effect on relieving the itch caused by atopic dermatitis and repairing damaged skin. These effects are obtained by combining the antipruritic, anti-inflammatory, moisturizing, skin barrier analogs, and skin protection ingredients, resulting in superior results over the efficacy of a single regimen.

Description

Topical composition for lowering pruritus or damaged skin barrier caused by atopic dermatitis}

The present invention relates to a composition for external application of the skin, which shows an itching relief effect associated with atopic dermatitis and excellent efficacy in repairing damaged skin. More specifically, by using an external skin composition of a liposome formulation selected from the group consisting of an itch relieving agent, an anti-inflammatory agent, a moisturizing agent, a skin barrier analogue, and a skin protectant, it is possible to obtain an excellent effect on relieving itching and damaged skin caused by atopic dermatitis. Can be. These effects are obtained by combining the antipruritic, anti-inflammatory, moisturizing, skin barrier analogs, and skin protection ingredients, resulting in superior results over the efficacy of a single regimen.

Atopic dermatitis occurs in about 10 to 20% of the entire Korean population, especially in children. After 5 years of age, the incidence decreases and many people disappear or alleviate the symptoms. Shows. As industrialization progresses rapidly, the probability of exposing external stimulants due to a clean living environment is lowered. Accordingly, the number of patients with atopic dermatitis due to the immune system is increasing by more than 10% every year. Although no clear model of the cause of the invention is known, the amount of immunoglobulin E (IgE) increases rapidly in patients with atopic dermatitis, while the amount of gamma interferon decreases.

Atopic dermatitis is characterized by a large amount of water evaporates from the surface of the skin, so that the skin is easily dried, and the acidity of the skin is higher than that of normal skin. In addition, due to the decrease of the lipid content of the stratum corneum, the antimicrobial activity is reduced and the barrier function is weakened. Therefore, an inflammatory reaction caused by an external irritant occurs and itching occurs. Scratching of the itchy area causes a secondary infection, which leads to a vicious cycle of hyperimmune reactions.

Looking at the prior art for the external skin composition for alleviating the symptoms of atopic dermatitis, as a single-effect formulation, aspirin-applied technology (Korean Patent Application No. 10-2002-7008214) has been developed, and has been described as alkanolamine, tyrosine and mixtures thereof. There is an example of applying a composition selected from the group consisting of to improve inflammation (Korean Patent Application No. 10-2001-0060816). In addition, the patent (Application No. PCT / JP1999 / 02883) filed by Nippon Yushi Co., Ltd. (application number PCT / JP1999 / 02883) shows that the content of w-3 unsaturated fatty acids is four times or more than the content of w-6 unsaturated fatty acids, and phosphoryl choline similar groups. There is a case of applying to atopic dermatitis as a composition containing a containing polymer and an antioxidant. There are many other examples of this, but rarely prescribes substances that are effective in alleviating itching, anti-inflammatory, increasing skin moisturization, protecting the damaged skin barrier through skin barrier analogs, and normalizing skin immune function. Although the formulation is expected to be expected (Korean Patent Application No. 10-2000-0075653), an effective concentration formulation for skin penetration of the active ingredient cannot be expected to stabilize the formulation with a simple formulation. In order to achieve the correct efficacy, the effective concentration is increased. In such a case, the formulation becomes more unstable and the skin permeability of the active ingredient is reduced.

In order to solve the above problems, the present invention prescribes a combination of natural ingredients that are effective in alleviating skin itch, natural ingredients for protecting and repairing the skin barrier, and natural ingredients that can enhance skin moisturizing, The formulation of the liposome structure for permeation and stability of the formulation was completed. It is an object of the present invention to provide a skin-friendly composition that can relieve skin itch and increase skin barrier repair function through such a composite prescription formulation.

1 is an electron micrograph of a liposome formulation composition embodied through the present invention.

2 is a view of atopic dermatitis patients, before using the composition embodied through the present invention

This picture shows the skin condition.

3 is atopic dermatitis after using the embodied composition embodied through the present invention

This picture shows the patient's improved skin condition.

In order to achieve the above object, in the present invention

a) itching suppression component

b) anti-inflammatory components

c) moisturizing ingredients

d) skin protection ingredients

e) skin barrier-like ingredients

It provides a skin external composition for improving atopic dermatitis, characterized in that it contains. Hereinafter, the present invention will be described in more detail.

The detail of each component is as follows.

A substance that can be used for anti-pruritic efficacy, with no special restrictions, but consisting of chamomile extract, scutellaria baicalesis, rosemarinus officinalis extract, green tea extract, and mixtures thereof It is preferably selected from the group. The content for showing efficacy is preferably 1.0 to 11.0% by weight.

There is no particular limitation as a substance that can be used for anti-inflammatory efficacy, but it is preferably selected from the group consisting of Japanese Knokweed extract, Centella asiatica, and mixtures thereof. The content for showing efficacy is preferably 1.0 to 11.0% by weight.

There is no particular restriction as to the substance that can be used as a moisturizer component, but it is preferably selected from the group consisting of Trehalose, Sodium 시 에 C (Na-PCA), Hyuronic acid, and mixtures thereof. The content for showing efficacy is preferably 1.0 to 11.0% by weight.

There are no specific restrictions on the substances that can be used as skin barrier analogues, but lecithin, cholesterol, phytospingosine, ceramide, borage oil, evening primrose oil and these It is preferably selected from the group consisting of a mixture of The content for showing efficacy is preferably 1.0 to 13.0% by weight.

It is a substance that can be used as a skin protectant, but there is no special limitation, but it is composed of Dipotassium Glycyrrhizinate extract, retinol, ascorbic acid, vitamin E, pantenol (pro vitamin B5) and mixtures thereof It is preferable to select from the group which becomes. The content for showing efficacy is preferably 1.0 to 20.0% by weight.

The content of the components is also a content for skin physiological efficacy of each component, but is a concentration for stabilizing the formulation due to the physical properties of the liposome structure.

Hereinafter, the present invention will be described in detail through the following examples and comparative examples. These examples are only for illustrating the present invention, and the present invention is not limited thereto.

EXAMPLE

Looking at the preparation of the extracts used in the present invention.

1 kg of leaves or roots of Centella Asiatica L. are chopped with a mill, and 100 kg of 70% ethanol is added and heated and extracted at 100 ° C. for 4 hours using a device equipped with a reflux device. The extracted solution was filtered using a filter aid, left to stand in a cold place for 7-10 days to mature, and then the precipitate was filtered and 70% ethanol was added to obtain 100 kg of product.

1kg of chamomile recutita, an asteraceae plant, is shredded with a mill, and 100kg of purified water is extracted for 4 hours at 100 ° C. The extracted filtrate is filtered using a filter aid, the filtrate is left to mature in a cold place for 7-10 days, then aged. The precipitate is filtered and purified water is added again to obtain 100 kg of the final product.

1kg polygonum cuspidatum, which is a knotweed plant, is shredded with a milling machine, and 100kg of 10% ethanol is extracted for 4 hours at 100 ° C. The extracted solution is filtered using a filter aid, and then 10% ethanol is added to obtain 100 kg of the final product.

1 kg of leaves of green tea (camellia sinensis) or other homogeneous plants are chopped, and 100 kg of 10% ethanol is added thereto, followed by 4 hours of heat extraction at 100 ° C. for filtration, and the filtrate is left to cool for 7-10 days to mature and then precipitates. Filtered and 10% ethanol was added to obtain 100 kg of final product.

1 kg of licorice (licorice) or other cognate plants are chopped, and 100 kg of purified water is added thereto, heated and extracted at 100 ° C. for 1 hour, and filtered. The precipitate of the aged filtrate is filtered and then purified water is added to obtain 100 kg of the final product.

Stems and roots of rosemary (Rosemarinus officinalis) are dried and chopped, ethanol is added to 10 times the volume of the sample, extracted at room temperature for 24 hours, filtered and the filtrate is concentrated in a reduced pressure concentrator, and then powdered.

Based on the components described in Table 1, the extract and the active ingredients are completed in the following manner. After the oil phase and the water phase are each prepared in a 65 degree blender, the oil phase is emulsified using a homomixer while gradually adding the oil phase to the water phase. In particular, the lecithin-containing oil phase is liposome inclusion capacity is lowered if left at high temperature for a long time, so first melt the ceramides at 75 degrees first, then cool to 65 degrees and participate in lecithin and vitamins to complete the oil phase in a short time. Mixing with a homo mixer is performed at 3000 rpm for 15 minutes. The finished formulation forms a liposome structure, which was confirmed by scanning electron microscopy (see FIG. 1).

Efficacy Group Raw material name Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Appeal Chamomile extract 2.0 1.0 0.2 1.0 - - - Golden extract 2.0 1.0 0.2 1.0 - - - Rosemary Extract 5.0 2.5 0.5 2.5 - - - Green tea extract 2.0 1.0 0.2 1.0 - - - Anti-inflammatory Centella extract 5.5 2.0 0.5 - 2.0 - - Soybean Extract 5.5 2.0 0.5 - 2.0 - - Moisturizing Trehalose 3.0 1.5 0.3 - - 1.5 - Sodium Fish 4.0 2.0 0.4 - - 2.0 - Hyaluronic acid 4.0 2.0 0.4 - - 2.0 - Skin barrier analogues lecithin 4.0 1.5 0.3 - - - 1.5 cholesterol 2.0 0.75 0.15 - - - 0.75 Phytosphingosine 0.8 0.50 0.10 - - - 0.50 Ceramide 1.8 0.75 0.15 - - - 0.75 Borage 2.0 0.75 0.15 - - - 0.75 Moonlight 2.0 0.75 0.15 - - - 0.75 Skin protection Licorice extract 8.0 4.0 0.4 4.0 4.0 4.0 4.0 Retinol 2.0 1.0 0.1 1.0 1.0 1.0 1.0 Vitamin c 2.0 1.0 0.1 1.0 1.0 1.0 1.0 Vitamin E 2.0 1.0 0.1 1.0 1.0 1.0 1.0 Pantenol 6.0 3.0 0.3 3.0 3.0 3.0 3.0 Etc Shea Butter 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Mango Butter 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Butylene Glycol 2.0 2.0 2.0 2.0 2.0 2.0 2.0 ethanol 2.0 2.0 2.0 2.0 2.0 2.0 2.0 IDT 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Potassium hydroxide 0.18 0.18 0.18 0.18 0.18 0.18 0.18 antiseptic Quantity Quantity Quantity Quantity Quantity Quantity Quantity Purified water To 100 To 100 To 100 To 100 To 100 To 100 To 100

The following analytical tests were performed to evaluate the efficacy on the skin physiology of the compositions embodied through the above Examples and Comparative Examples, particularly on the general physiological phenomena of atopic dermatitis symptoms.

In order to test the effect of reducing itch, the degree of production of the histamine component, an itch-related in vivo substance, was measured. The measuring method was performed according to Korean patent (application number 10-2000-0079338). Itching effect should be more than 20% histamine free inhibition.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Histamine release rate 98.7 95.4 94.1 95.2 4.2 5.9 3.8

The effect on relieving itching is high regardless of the concentrations of 11%, 5.5%, and 1.1% of Examples 1, 2 and 3 or 5.5% of Comparative Examples 2, 3, 4, and 5, but only in Comparative Example 1. Its absence of ingredients does not inhibit histamine release.

For testing the moisturizing power of the composition according to the present invention using a Corneometer (model name CM820) was measured before and after sample treatment. The measuring method was as described in the Republic of Korea Patent (Application No. 10-2001-0010689). The relative residual moisture content was calculated by measuring the moisture content of the skin immediately after application and after a certain time after application of the product. The results are as follows.

Minutes Water (control) Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 0 100 100 100 100 100 100 100 100 5 88.1 99.1 98.3 98.5 87.6 87.9 98.5 88.2 30 11.5 32.7 35.7 30.5 10.9 13.1 33.7 12.1 60 2.7 11.5 13.7 10.3 1.9 2.1 15.5 1.4

According to the results, in the case of Examples 1, 2, 3 and Comparative Example 3 containing the moisturizing component showed a moisturizing power 3-5 times higher than the moisturizing power when water is simply applied to the skin.

In order to evaluate the anti-inflammatory efficacy, a method described in Korean Patent Application No. 10-1999-0050633 was used. According to the described method, Tetracanocanoylphorbol acetate (TPA) is dissolved in acetone and applied to the ICR mouse ears to induce edema, and each product is applied 15 minutes, 6 hours after induction of edema (30 mg / kg). 24 hours after application, a portion of the mouse ear was cut out, and then the weight of the ear was measured and the anti-inflammatory effect was measured by measuring the myeloperoxidase activity. The measurement results are as follows.

Aspirin (control) Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Sample concentration (mg / ear) 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Suppression rate 38 43 40 38 1.0 41 1.5 1.1

The anti-inflammatory efficacy of the preparations according to the invention appeared similar to the anti-inflammatory efficacy of aspirin as seen in the above results.

Sensitive or dry skin and 50 children and adults with mild atopic dermatitis were examined for improvement of symptoms after use of the compositions according to the examples. Duration of use averages about one week and is used for 25 children aged 0 to 9 years and 25 children over 10 years old. Extent, 5) the extent of overall skin recovery was interviewed.

division Symptom Improvement after use (%) worse usually Improving Excellent Infant Itching 0 16 33 51 Itching During Sleep 0 0 50 50 Dry skin 0 0 33 67 Redness / dust 0 0 71 29 Overall skin condition 0 16 67 16 Adult Itching 0 0 50 50 Itching During Sleep 0 0 65 35 Dry skin 0 48 45 7 Redness / dust 0 0 65 35 Overall skin condition 0 0 55 45

As a result, the overall improvement of skin was 96% (significant improvement 35%, slight improvement 61%), which showed clear improvement of symptoms, especially in children with atopic infection.

In order to evaluate the utility of single-drug prescriptions (Comparative Examples 1, 2, 3, 4) and multi-dose formulations (Examples 1, 2, 3), clinical trials were conducted for single- and multi-dose formulations. . The clinical results were obtained from 50 children under 10 years of age with mild atopic dermatitis.

Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Itching 80 80 0 0 0 Itching During Sleep 100 100 0 0 0 Dry skin 100 40 40 100 40 Redness / dust 100 60 60 30 40 General skin condition 80 50 50 50 70

According to the above clinical results, a single prescription of antipruritic, anti-inflammatory, moisturizing and skin barrier analogs based on itching, sleeping itch, skin dryness and redness / skin rash symptoms common to atopic dermatitis It can be concluded that symptom improvement is further increased in the case of the mixed prescription (Example 2) in which each component is all mixed than when Examples 1, 2, 3, and 4) are clinically applied.

The external composition for skin embodied through the present invention shows an excellent effect on the recovery of damaged skin caused by scratching the inflammatory response and the itchy area due to the infection as well as the itch relief effect due to atopic dermatitis.

Claims (13)

The composition for external application of skin containing 0.01 to 50.0% by weight, based on the total amount of the ingredients, selected from the group consisting of itching, anti-inflammatory, moisturizing agent, skin barrier analogue, and skin protectant The composition for external application of skin according to claim 1, which is selected from the group consisting of chamomile extract, chamomile extract, scutellaria baicalesis, rosemarinus officinalis extract, green tea extract as an itch relieving agent. The composition for external application of skin according to claim 1, which is selected from the group consisting of Japanese Knokweed extract and Centella asiatica as an anti-inflammatory agent. The composition for external application of skin according to claim 1, which is selected from the group consisting of Trehalose, Sodium Bacterium (Na-PCA), and Hyururonic acid as a moisturizing ingredient. The method of claim 1, wherein the skin barrier analogue is selected from the group consisting of lecithin, cholesterol, phytospingosine, ceramide, borage oil, evening primrose oil. Skin external composition The composition for external application of skin according to claim 1, which is selected from the group consisting of dipotassium Glycyrrhizinate extract, retinol, ascorbic acid, vitamin E, and pro vitamin B5 as a skin protectant. The method of claim 2, wherein the effective concentration for itch relief efficacy is 1.0 to 11.0 Weight percent. The method of claim 3, wherein the effective concentration for anti-inflammatory efficacy is from 1.0 to 11.0 weight percent. The method of claim 4, wherein the effective concentration for moisturizing efficacy is 1.0 to 11.0% by weight. The method of claim 5, wherein the effective concentration for skin barrier analog efficacy is between 1.0 and 13.0. Weight percent. 7. The effective concentration of claim 6, wherein the effective concentration for skin protective effect is 1.0 to 20.0%. The composition of claim 1 is used for the purpose of improving atopic dermatitis, seborrheic dermatitis, and dry skin. The topical skin preparation according to claim 1, which is embodied in a lotion, cream, essence, soap, patch formulation.