KR102581609B1 - Composition of skin external application for improving atopic dermatitis comprising allicin - Google Patents

Abstract

The present invention relates to a composition for topical skin application for the treatment of atopic dermatitis, and more specifically, it contains allicin and citron extract as active ingredients. The external skin composition for the treatment of atopic dermatitis containing allicin of the present invention has the advantage of ultimately improving atopic dermatitis by inhibiting the expression of TSLP and sterilizing staphylococci.

Description

Composition for skin external application for the treatment of atopic dermatitis containing allicin {COMPOSITION OF SKIN EXTERNAL APPLICATION FOR IMPROVING ATOPIC DERMATITIS COMPRISING ALLICIN}

The present invention relates to a composition for external application to the skin for the treatment of atopic dermatitis, and more specifically, to a composition for external application to the skin for the treatment of atopic dermatitis using allicin as an active ingredient.

Atopic dermatitis is a skin disease that presents as a chronic inflammatory skin condition with severe itching. It usually appears in infancy and childhood and may persist into adulthood or throughout life. The induction rate is 10-20% in children and 1-3% in adults, and this has increased 2-3 times over the past 30 years. Recently, the induction rate has been increasing in adults as well. Atopic dermatitis can cause insomnia, emotional disorders, learning disabilities, and difficulties in social activities. It is known that complex factors such as immunological, physiological, and biochemical triggers as well as genetic factors are involved. The cause is not clearly known (Park Young-rip et al., Journal of the Korean Society of Skin Research, 2007, 14(3), 67-72).

Extrinsic dermatitis, which accounts for 70-80% of atopic dermatitis, is caused by an IgE-related immune mechanism, and in this case, there are many reports that a delayed immune response due to T cell abnormalities is involved. In areas where atopic dermatitis occurs, the infiltration of immune-related cells such as macrophages, Th lymphocytes, and mast cells greatly increases. Atopic dermatitis skin has a high concentration of IgE in the blood in atopic dermatitis patients. This is because the number of Th2 cells increases and Th2 cytokines such as IL-4 and 13 secreted by these cells promote IgE secretion through stimulation of B lymphocytes. am. In particular, in the case of early atopic dermatitis, IL-4 and IL-13 play an important role (Donald YM Leung et al, J Clin Invest 2004, 113, 651-657).

According to recent reports, thymic stromal lymphopoietin (TSLP) is known to play an important role in atopic dermatitis. This is because the concentration of TSLP is increased in keratinocytes of atopic dermatitis patients, while the concentration is similar to normal in other dermatitis, and is known to be a specific factor in atopic dermatitis. TSLP increases due to increased pro-inflammatory cytokines and Th2 cytokines in keratinocytes exposed to physical and chemical stimuli (Eric B Brandt etal J Clin Cell Immunol, 2011, 2(3)). This increased TSLP activates CD11c+ dendritic cells, and the activated dendritic cells promote the secretion of Th2 cytokines such as thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) from T cells (Sarah R et al, Cell, 155, 285-295).

In addition, Staphylococcus aureus is also reported as one of the causes of atopic dermatitis.

To treat atopic dermatitis, apply moisturizer consistently, and in severe cases, prescribe steroid ointment or antihistamines. This has the effect of temporarily relieving symptoms, but long-term use of steroid hormones can cause skin atrophy or capillaries to expand, and can actually cause side effects such as weakening of the skin barrier function and causing osteoporosis. Therefore, there is a need for the development of an atopy treatment with a new mechanism that has excellent effects and fewer side effects.

Meanwhile, allicin is a representative component of garlic, and allin is converted to allicin by allinase. Allicin has strong sterilizing, antibacterial, whitening, and antioxidant effects, and has even higher medicinal efficacy by combining with carbohydrates, lipids, and proteins. Allicin is contained in many plants in the lily family, such as garlic, onions, green onions, chives, and chives.

The allicin is widely used in various cosmetic compositions due to its strong sterilizing and antibacterial effects, whitening action, and antioxidant activity.

However, nowhere in the prior literature was there an example of application for the improvement of atopic dermatitis.

KR 10-1458758 B1 KR 10-2316909 B1

Therefore, the object of the present invention is to treat atopic dermatitis containing allicin, which has the effect of improving atopic dermatitis by inhibiting the expression of TSLP, a cytokine that acts as one of the causes of atopic dermatitis, and inhibiting the activity of Staphylococcus aureus. The object is to provide a composition for external application to the skin.

A composition for topical skin application for the treatment of atopic dermatitis containing allicin to achieve the above object is characterized by containing allicin and citron extract as active ingredients.

The active ingredient is characterized by inhibiting the expression of TSLP (thymic stromal lymphopoietin), one of the causes of atopic dermatitis.

The active ingredient is characterized by having antibacterial activity against Staphylococcus aureus, one of the causes of atopic dermatitis.

It is characterized in that it further contains pink celandine extract as an active ingredient.

It is characterized in that it further contains olive liquid, hyaluronic acid, nucleic acid, ethanol and distilled water.

It is characterized in that it contains 10 to 30 parts by weight of citron extract based on 100 parts by weight of allicin.

The external skin composition for the treatment of atopic dermatitis containing allicin of the present invention has the advantage of ultimately improving atopic dermatitis by inhibiting the expression of TSLP and sterilizing staphylococci.

1 to 3 are graphs showing the results of Test Example 1 according to the present invention.

Hereinafter, the present invention will be described in more detail.

Conventionally, most topical drugs for the treatment of atopic dermatitis have a moisturizing effect, and this moisturizing effect alone has limitations in improving atopic dermatitis. The greatest feature of the present invention is that it can ultimately improve atopic dermatitis by suppressing the expression of TSLP and sterilizing staphylococci.

The composition for topical skin application for the treatment of atopic dermatitis of the present invention is characterized by containing garlic juice and citron extract containing allicin as active ingredients.

First, allicin is a representative component of garlic, and allin is changed into allicin by allinase. Allicin has strong bactericidal and antibacterial effects.

Allicin is contained in many plants in the lily family, such as garlic, onions, green onions, chives, and wild chives. In the present invention, artificially produced allicin can be used, but natural allicin extracted from the Liliaceae plants can also be used. In particular, juice of the Liliaceae plants, most preferably garlic juice, is preferably used as a source of allicin. You can.

The citron extract has excellent anti-inflammatory properties and helps achieve atopic dermatitis treatment due to its rich vitamin organic acids. Compared to other citrus fruits, yuzu is not only rich in vitamins B1, B2, C, various organic acids, carbohydrates, and proteins, but also contains limonoid and anti-inflammatory properties known to have excellent anti-cancer effects. It is rich in hesperidin, which is known to have antibacterial effects. In particular, allicin has a higher sterilizing and antibacterial effect when combined with carbohydrates, proteins, etc., so the effect is maximized when used in combination with citron extract.

In the present invention, the extraction method of the citron extract is not limited, and 2 to 10 times by volume of water, ethanol or a mixed solvent thereof is added to the citron fruit, and extraction, filtration, concentration and drying are performed at 20 to 100° C. for 2 to 10 hours. It can be manufactured. It goes without saying that the filtration, concentration and drying methods can use various methods known in the art.

The citron extract may be included in an amount of 10 to 30 parts by weight based on 100 parts by weight of the garlic juice. If it is less than 10 parts by weight, the effect of improving atopic dermatitis is minimal, and even if it exceeds 30 parts by weight, the improved effect can no longer be obtained. am.

In the present invention, when the garlic juice and the citron extract are included as active ingredients, the expression of TSLP, a cytokine that acts as one of the causes of atopic dermatitis, can be significantly suppressed compared to using the garlic juice alone, It can exert strong antibacterial activity against Staphylococcus aureus, another cause.

That is, the external skin composition for the treatment of atopic dermatitis containing garlic juice and citron extract according to the present invention as active ingredients inhibits the expression of TSLP (thymic stromal lymphopoietin), one of the causes of atopic dermatitis, and is one of the causes of atopic dermatitis. Another advantage is that it has strong antibacterial activity against Staphylococcus aureus and can fundamentally improve atopic dermatitis.

In addition, the composition for topical skin application for the treatment of atopic dermatitis according to the present invention preferably further contains a pink celandine extract as an active ingredient.

When only the garlic juice and citron extract are included as active ingredients, it does not provide a sufficient moisturizing effect, and when using external preparations, there may be irritation such as skin stinging at the beginning of application. However, if the pink celandine extract is further included as an active ingredient, a sufficient moisturizing effect is provided. This is because it can also relieve skin irritation.

The pink celandine (Binghamia californica J Agardh) is a seaweed of the red algae plant, Binghamia family, and grows in the lower intertidal zone. The plant body is membranous, pink, and has several flat stems growing from thin, rope-shaped roots.

The extraction method of the pink celandine extract is not limited, and may include adding 2 to 10 times the volume of water, ethanol or a mixed solvent thereof to the pink celandine extract, extracting, filtering, concentrating and drying at 20 to 100°C for 2 to 10 hours. there is. The filtration, concentration and drying methods use various methods known in the art.

The pink celandine extract is preferably included in an amount of 10 to 20 parts by weight based on 100 parts by weight of the garlic juice. If it is less than 10 parts by weight, the effect of moisturizing and alleviating irritation is minimal, and if it exceeds 20 parts by weight, the effect of improving atopic dermatitis is rather poor. Because it can fall.

In addition, the external skin composition for treating atopic dermatitis of the present invention may further include olive liquid, hyaluronic acid, nucleic acid, ethanol, and distilled water.

The olive liquid is sodium PEG-7 olive oil carboxylate, which provides adequate moisturizing without irritating the skin and also functions as a natural emulsifier. Therefore, Olive Liquid also plays a role in ensuring that allicin and other ingredients are well mixed without being separated.

The nucleic acid is the main body of genes that exist in the cells of all living things. It promotes metabolism and has excellent antioxidant properties, preventing aging, strengthening skin regeneration, and has excellent anti-inflammatory and wound healing effects. . Therefore, it heals wounds caused by atopic dermatitis.

The hyaluronic acid is a natural polymer that exists in large quantities in the skin of animals, etc., and is present in the living body in the epidermis, cartilage, vitreous humor of the eye, synovial fluid of joints, etc., and is used to maintain the structure of the skin and function normally. plays an important role.

The ethanol functions to disinfect wounds and prevent deterioration of the composition according to the present invention. In addition, when the composition for the present invention is applied to the skin, it volatilizes and reduces heat, thereby reducing pain, itching, etc.

And distilled water adjusts the overall concentration and viscosity of the composition.

At this time, based on 100 parts by weight of the garlic juice, the content is 200 to 300 parts by weight of olive liquid, 1 to 10 parts by weight of nucleic acid, 1 to 10 parts by weight of hyaluronic acid, 100 to 500 parts by weight of ethanol, and 50 to 150 parts by weight of distilled water. It may be included, but is not necessarily limited.

In the present invention, the composition for external use includes skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, ointment, foundation, essence, nutritional essence. , it may have one or more formulations selected from the group consisting of packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions, and body cleansers, but is not limited thereto. In addition, it can be applied in various forms such as liquid, cream, paste, and solid.

In addition, for the formulation, various additives known in the art may be added, but this is not limited. In addition, when formulating, the total active ingredients including allicin may be included in an amount of 5 to 100% by weight based on 100% by weight of the total composition, but this is also not limited.

Hereinafter, the present invention will be described in detail through specific examples.

(Example 1)

100g of garlic juice containing allicin and 20g of citron extract were mixed.

At this time, the citron extract was obtained by pulverizing the citron fruit, adding 5 times by volume of 50% ethanol, followed by reflux-cooled boiling extraction three times for 3 hours at 80°C, and concentrating with a vacuum concentrator at 40°C. An extract was prepared by drying.

(Example 2)

The same procedure as in Example 1 was carried out, but 20 g of pink celandine extract was further mixed.

The pink celandine extract was prepared by adding 5 volumes of 50% ethanol to the pink celandine plant, extracting it with reflux-cooled boiling water three times for 3 hours at 80°C, concentrating with a vacuum concentrator at 40°C, and drying. did.

(Test Example 1)

TSLP, MDC, TARC inhibition test

TSLP (thymic stromal lymphopoietin) is classified as the top cytokine that initiates type 2 helper T cell-mediated immune bias, which is identified as the cause of atopic dermatitis. MDC and TARC are inflammatory chemokines and are downstream factors of TSLP.

In order to confirm the effect of Examples 1 and 2 on reducing the expression of cytokines and chemokines occurring in human keratinocytes HaCaT, the level of expression of each gene was evaluated.

Keratinocyte HaCaT, a cell line of human skin, was cultured using DMEM medium containing 10% fetal bovine serum (FBS) and antibiotics. A 75T-flask and 6 well plate were used as culture vessels, and cultured in a 37°C incubator supplied with 5% CO ₂ . The culture medium was changed every 3 to 4 days, and cells were subcultured when they proliferated excessively. Cells were dispensed into a 6-well plate, and after 24 hours of culture, washed with phosphate-buffered saline solution (PBS), and samples were added to each well along with Poly I:C and IL-4 in DMEM medium without FBS. It was diluted to a final concentration of 10ppm and added to each well. The positive control group was treated with 1uM of dexamethasone. After 4 hours, cDNA was synthesized and PCR was performed to evaluate the level of gene expression.

The synthesized cDNA was subjected to real-time polymerase chain reaction (PCR) using a target template and a cyanine dye, SYBR green master mix, to finally determine the gene expression level of TSLP. was evaluated. Expression of genes was compared as a relative value through corrected quantification of the internal control gene β-actin by the threshold cycle (Ct) method.

As a result, as shown in Figures 1 to 3, it was confirmed that TSLP, MDC, and TARC overexpressed by poly I:C and IL-4 were significantly suppressed depending on sample treatment.

Therefore, it was confirmed that Examples 1 and 2 of the present invention can treat and improve atopic dermatitis by inhibiting the expression of TSLP, which is directly or indirectly related to atopic dermatitis.

(Test Example 2)

Antibacterial activity against Staphylococcus aureus

To evaluate the antibacterial activity against Staphylococcus aureus KACC10768, a pathogenic strain that causes secondary infection of atopic dermatitis, the paper disc method using a multilayer medium was used using gentamicin as a control. .

For quantitative evaluation of antibacterial activity, soy casein digestion agar medium for Staphylococcus aureus culture (Tryptic soy agar 0.7%, casein peptone 15.0 g, soy peptone 5.0 g, sodium chloride 5.0 g, purified water 975 g, pH 7.2 ± 0.1) 100㎕ of Staphylococcus aureus strain was added, and 50㎕ of each sample was treated on a filter paper disk (9mm). Afterwards, the antibacterial activity was confirmed by culturing at 37°C for 48 hours and converting the diameter of the antibacterial activity range in which the strain did not proliferate into units (the diameter of the antibacterial activity range of gentamicin 10 mg/ml is defined as 1 unit). did. And the results are shown in Table 1 below.

Test Example 2 Results division Diameter (mm) unit Gentamicin 12 1.00 Example 1 20 1.66 Example 2 21 1.75 Comparative Example 1 12 1.00

As can be seen in Table 1, the diameter of the antibacterial activity range of gentamicin, which is a control group, was found to be 12 mm, and as a result of comparing this by defining it as 1 unit, it was confirmed that Examples 1 and 2 showed excellent antibacterial activity. I was able to.

Therefore, it was confirmed that Examples 1 and 2 of the present invention can be usefully used for the purpose of treating or improving atopic dermatitis and its secondary infections.

(Example 3)

100g of garlic juice containing allicin, 20g of citron extract, 250g of olive liquid, 5g of nucleic acid, 5g of hyaluronic acid, 300g of ethanol, and 100g of distilled water were mixed. At this time, garlic juice and citron extract were prepared in the same manner as Example 1.

(Example 4)

The same procedure as in Example 3 was carried out, but 20 g of pink celandine extract was further mixed. At this time, the pink celandine extract was prepared in the same way as Example 2.

(Test Example 3)

For 30 adult men and women with atopic dermatitis, Examples 1, 2, and the control group were distributed, and 1 ml was applied to the affected area twice a day for 10 days (each subject was divided into 3 areas and each sample was applied). ) was tested using the method. After application for 10 days, the atopy improvement effect, skin irritation level, and moisturizing effect were evaluated, and the results are shown as average values in Table 2 below. As a control group, a commercially available moisturizing cream for atopic dermatitis was provided.

Test Example 2 Results division Atopy improvement level of skin irritation Moisturizing overall satisfaction Example 1 4.2 4.6 3.0 4.5 Example 2 4.7 5.0 4.3 4.7 control group 2.8 5.0 4.0 3.1 5: Very improved, or no irritation at all.
4: Slight improvement, or slight irritation.
3: No improvement, or moderate irritation.
2: Slightly worse, or severe irritation.
1: Cannot be used because it is very aggravated or irritating.

As shown in Table 2, it was confirmed that Examples 1 and 2 of the present invention had a superior atopic dermatitis improvement effect compared to the control group.

From the above description, a person skilled in the art to which this application belongs will be able to understand that this application can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present application should be interpreted as including the meaning and scope of the patent claims described below rather than the detailed description above, and all changes or modified forms derived from the equivalent concept thereof are included in the scope of the present application.

Claims (6)

Contains garlic juice containing allicin, citron extract, and pink celandine extract as active ingredients,
Containing 10 to 30 parts by weight of citron extract and 10 to 20 parts by weight of pink celandine extract, based on 100 parts by weight of the garlic juice,
Based on 100 parts by weight of the garlic juice, 200 to 300 parts by weight of olive liquid, 1 to 10 parts by weight of nucleic acid, 1 to 10 parts by weight of hyaluronic acid, 100 to 500 parts by weight of ethanol, and 50 to 150 parts by weight of distilled water,
The active ingredient inhibits the expression of TSLP (thymic stromal lymphopoietin), one of the causes of atopic dermatitis,
The active ingredient is an external skin composition for improving atopic dermatitis, characterized in that it has antibacterial activity against Staphylococcus aureus, one of the causes of atopic dermatitis. delete delete delete delete delete