KR102394527B1 - Composition containing essential oil for relieving seborrheic dematitis - Google Patents

Abstract

The present invention relates to a composition for alleviating seborrheic scalp inflammation containing a natural fragrance as an active ingredient, and more specifically, to a composition for relieving seborrheic scalp inflammation by containing at least one natural fragrance selected from the group consisting of mandarin peel oil, gwanggwakhyang oil and pettigrain oil. Skin topical composition having no irritation and no side effects when used for a long period of time, inhibiting the proliferation and inflammation of the scalp flora, which is the cause of seborrheic scalp inflammation, and preventing and improving inflammation due to excessive sebum production and bacterial growth and degeneration is about

Description

Seborrheic scalp inflammation relief composition containing natural fragrance {Composition containing essential oil for relieving seborrheic dematitis}

The present invention relates to a composition for alleviating seborrheic scalp inflammation containing a natural fragrance as an active ingredient, and more specifically, to a composition for relieving seborrheic scalp inflammation by containing at least one natural fragrance selected from the group consisting of mandarin peel oil, gwanggwakhyang oil and pettigrain oil. Skin topical composition having no irritation and no side effects when used for a long period of time, inhibiting the proliferation and inflammation of the scalp flora, which is the cause of seborrheic scalp inflammation, and preventing and improving inflammation due to excessive sebum production and bacterial growth and degeneration is about

The dermal sebaceous glands are complete glands that secrete a mixture of lipids known as sebum. The term “sebum” refers to secretions of the sebaceous glands containing triglycerides, free fatty acids, wax esters, squalene, cholesterol and cholesteryl esters. When sebum is excessively produced in the sebaceous glands, oily skin appears, and may also cause the appearance of other skin disorders, diseases or conditions such as acne and seborrheic dermatitis.

Sebum production is regulated by factors affecting the proliferation and differentiation of sebaceous gland cells, and factors such as male hormone, female hormone, IGF-1 (insulin-like growth factor), and PPAR (peroxisome proliferatoractivated receptor) known to be related to The sebum produced by the sebaceous gland cells is secreted to the skin surface through the hair follicle duct, and the produced sebum is known to change the structure of keratinocyte intercellular lipid on the skin surface to lower the skin barrier function. It is known that overgrowth of seborrheic dermatitis and the like is the cause of seborrheic dermatitis and scalp inflammation. Therefore, proper removal of the generated sebum and suppression of sebum production are considered important for skin barrier function and maintenance of healthy skin.

As a method for suppressing sebum production, a substance that inhibits 5-alpha-reductase, which functions to convert testosterone, a male hormone, into dihydrotestosterone, has been developed and used. In addition, efforts are being made to suppress sebum production by transdermally applying an androgen receptor inhibitor (anti-androgen receptor) that inhibits the binding of testosterone to the receptor of dihydrotestosterone. However, these hormone inhibitors have difficulties in transdermal delivery, and even if they are effectively delivered by transdermal administration, there is a possibility that they may affect the hormonal balance of the whole body, so development is not easy.

On the other hand, in general, seborrheic dermatitis is a very common disease that occurs in 3 out of 10 people, and symptoms frequently occur not only on the face but also on the scalp.

Inflammation of the seborrheic scalp appears in the form of red and inflamed scalp, accompanied by dandruff or keratin, and itching. In severe cases, aged dead skin cells and wastes cover the entire scalp, and in severe cases, scalp pain and bad odors may occur. This seborrheic scalp inflammation is also a cause of seborrheic hair loss, but there is a problem with the sebaceous glands, and the amount of sebum secretion increases abnormally, and the increased sebum clogs the pores in the scalp, reducing scalp nutrition supply and circulation function, and seborrheic hair loss appears.

Seborrheic dermatitis is found in 1-3% of healthy adults and 83% of immunocompromised patients (such as AIDS). The cause of infection has not been identified, and many investigations have reported that Malassezia is related, but it is not conclusive, and Malassezia restricta and Malassezia are It has been reported that globosa is mainly found in the skin affected by seborrheic scalpitis, and the hypothesis is that the cause of SD/dandruff is that Malassezia bacteria break down triglycerides to produce irritant fatty acids. there is.

Since it has been shown that fatty acids produced by the Malassezia bacteria decomposing lipids through lipase cause irritation in the scalp, M. globosa lipase plays a very important role in the development of dandruff. When lipids are decomposed by lipase to produce fatty acids, they penetrate the keratin, destroying the skin barrier and causing inflammation.

As a treatment for seborrheic scalpitis, it mainly focuses on Malassezia-specific or non-specific antibacterial agents. As drugs, a wide range of anti-inflammatory drugs such as Ketoconazole and Terbinafin are used. However, since these antibacterial agents are limited to pharmaceuticals, there is a need for an antibacterial and anti-inflammatory material that can be applied to cosmetics and detergents, and accordingly, in the present invention, a material capable of suppressing the symptoms of seborrheic scalpitis and killing the causative organism is provided. A study was conducted to explore.

Publication of domestic patent application 10-2013-0059536 (published on June 7, 2013)

The present inventors use a natural fragrance to prevent irritation to the skin, no side effects when used for a long period of time, suppress the proliferation and inflammation of the scalp flora, which is the cause of seborrheic scalp inflammation, and reduce inflammation due to excessive sebum production and bacterial growth and degeneration. A skin external preparation with excellent prevention and improvement effects was completed.

Accordingly, an object of the present invention is to provide a composition that is helpful in suppressing excessive production of sebum, improving symptoms of seborrheic scalpitis, and inhibiting progression.

In order to achieve the above object, the present invention provides a composition for controlling sebum on the scalp containing at least one natural fragrance selected from the group consisting of mandarin peel oil, gwanggwakhyang oil and pettigrain oil as an active ingredient.

Since the composition according to the present invention contains essential oils derived from nature, there is no irritation to the skin, no side effects even when used for a long period of time on the human body, and it is effective in preventing and improving inflammation due to excessive production of sebum on the scalp and proliferation and degeneration of bacteria It is effective in suppressing the progression of seborrhea and seborrheic scalpitis and improving symptoms.

In addition, since the composition according to the present invention can be formulated as an external application that can be applied to the scalp and skin, it can be utilized in various cosmetic or pharmaceutical fields.

1 is a graph showing the inhibitory efficacy of inflammatory cytokines of oil according to the present invention.
2 is a graph showing the sebum production control efficacy of the oil according to the present invention.

The present invention provides a composition for improving scalp and hair conditions by containing at least one natural fragrance selected from the group consisting of mandarin peel oil, gwanggwakhyang oil and pettigrain oil as an active ingredient, in particular, inhibiting scalp sebum or seborrheic scalp A composition effective for inhibiting inflammation is provided.

Mandarin peel oil used in the present invention is derived from the peel of mandarin (Madarin; Citrus reticulate ), and mandarin is a generic term for rutaceae and mandarin-based tangerines. As a representative alkaline food, mandarin helps to prevent colds by smoothing metabolism and strengthening skin and mucous membranes, and is also effective in protecting capillaries and preventing high blood pressure. The mandarin peel oil can be obtained from mandarin using a conventional method in the art. For example, it can be obtained by pressing from mandarin peel.

Gwanggwakhyang used in the present invention (Patchouly; Pogostemon ) cablin ) is a plant of the Lamiaceae family, known to be effective in preventing skin aging, and is used for skin care such as wounds, scars, disinfection, or alleviation of symptoms related to depression, anxiety, and stress.

Petigrain oil used in the present invention is Citrus aurantium var. It is obtained by steam distillation together with the leaves or twigs of amara or unripe fruits. It is mainly used in the combination of soap flavoring and perfume.

The content of each of mandarin peel oil, gwanggwakhyang oil, or pettigrain oil used in the composition according to an embodiment of the present invention may be contained in an amount of 0.001 to 5% by weight based on the total weight of the composition. When used in the above range, there is a significant effect upon cumulative use, and excellent efficacy can be exhibited without skin irritation.

The composition according to the present invention is recognized for its efficacy in controlling sebum.

The composition according to the present invention reduces seborrheic scalp inflammatory cytokines and/or seborrheic scalp inflammatory causative bacteria, particularly Malassezia The efficacy of preventing or inhibiting the proliferation of globosa is recognized. Because it contains natural essential oil as the main ingredient, it is safe for the human body, does not irritate the skin, and has no side effects even after long-term use.

The composition of the present invention may be utilized without particular limitation in various fields, for example, may be formulated as an external preparation for the skin, and specifically may be formulated in the form of a cosmetic or pharmaceutical composition.

The composition of the present invention is not particularly limited in formulating, but it can be formulated as a hair tonic, hair nourishing lotion, scalp treatment, hair treatment, hair rinse, hair shampoo, hair lotion or scalp and hair combination treatment. there is.

In addition, in each formulation, other components other than the above essential components can be suitably selected and formulated by those skilled in the art without difficulty depending on the type or purpose of use of other external preparations.

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples. However, the following examples and test examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

[Preparation Example 1] Preparation of mandarin peel oil

After collecting 1 kg of mandarin peels and pressing strongly, all the juices were collected and put in a centrifuge and rotated at about 5,000 rpm for 10 minutes. Then, the oil of the upper layer was separated using a separatory funnel to obtain 0.75 g of oil.

[Preparation Example 2] Preparation of Gwanggwakhyang Oil

Approximately 1 kg of Gwanggwakhyang leaves were dried in the shade for about 12 hours, placed in a distillation container, sealed, and then steam at a temperature of about 100~120℃ was blown for 3 hours to obtain 0.25g of Gwanggwakhyang oil.

[Preparation Example 3] Preparation of pettigrain oil

After putting 2 kg of the leaves and branches of the pettigrain tree in a distillation container, sealing it, and blowing steam at a temperature of about 100 to 120° C. for 4 hours, about 1.0 g of pettigrain bitter orange leaf oil was obtained.

[Reference Example] Cell culture conditions

Hamster sebocytes were harvested from the sebaceous glands of the ears of 5-week-old male golden hamsters. For the specific extraction method, the paper of Sato et al. (J Invest Dermatol 2001, 117:965-70) was referred to. The extracted sebaceous gland cells were cultured in a culture flask, so as to be 2.35x10 ⁴ pieces/cm ² .

The culture medium was DMEM/Ham's F12 medium; (1:1) (DMEM/F12) (Invitrogen, Carlsbad, CA)) with fetal bovine serum; JRH Bioscience, Tokyo, Japan). 10% was added, and 0.68 mM of L-glutamine (Lglutamine; Invitrogen) and 10 nM of rhEGF (recombinant human epidermal growth factor; Progen Biotechnik GmbH, Heidelberg, Germany) were added.

As antibiotics, penicillin 100 mg/ml and streptomycin 100 mg/ml (all obtained from GIBCO (Milan, Italy)) were used together. The hamster sebaceous gland cells took 24 hours to completely attach to the culture flask, and were cultured at 37° C., 5% CO ₂ .

HaCaT, a human-derived keratinocyte cell line, is obtained by adding 10% of fetal bovine serum (JRH Bioscience, Tokyo, Japan) to DMEM medium (Invitrogen, Carlsbad, CA), penicillin 100 mg/ml, strepto Mycin 100 mg/ml (all from GIBCO, Milan, Italy) was used, and cultured at 37° C., 5% CO ₂ conditions was used.

[Test Example 1] Seborrheic scalp inflammation inhibitory effect - In vitro evaluation

In order to efficiently evaluate the inhibitory effect of natural fragrances on seborrheic scalp inflammation, an in vitro inflammatory model in an environment similar to human seborrheic scalp inflammatory lesions using sebaceous gland cells and keratinocytes was used. HaCaT human keratinocytes and human sebaceous gland cells (Celprogen, USA) were inoculated into a 24-well culture plate by 3x10 ⁴ and 3x10 ⁴ cells, respectively. After inoculation, we waited one day to allow the cells to attach to the bottom of the culture plate. In this case, as the medium, sebocyte culture complete media (Celprogen, USA) was used.

As an irritant to cause seborrheic scalp inflammation in cells after a day, 50 μM of linoleic acid that promotes sebum production, 50 μM of arachidonic acid that stimulates inflammation and free fatty acid production, 10 nM of dihydrotestosterone, Seborrheic scalp inflammatory bacteria ( Malassezia globosa ) was treated with 1% (v/v) in the cell line culture medium at 2ng/ml. At the same time, the mandarin peel oil, Gwanggwakhyang oil, and pettigrain oil of Preparation Examples 1 to 3 were treated at 1ppm or 3ppm, respectively, to observe the effect of inhibiting seborrheic scalp inflammation due to the irritant.

As a negative control, an untreated cell group was used, and as a positive control, 10 μg/ml (10 ppm) of indomethacin, a non-steroidal anti-inflammatory drug widely used as an inhibitor of general inflammation including soothing scalp inflammation, was applied to the cells. ) was used. ELISA (enzyme-linked immunosorbent assay) was performed to measure the concentration of IL-8 (interleukin-8), a post-inflammatory cytokine, expressed in the culture medium after one day after treatment with the stimulator and control drug or fragrance was measured in 10 μl of medium. BD Bioscience Human IL-8 ELISA set (cat.no. 555244) was used for ELISA, and the experiment was performed according to the manufacturer's recommended method.

The analysis results are shown in FIG. 1 . Referring to FIG. 1 , it can be confirmed that the perfume oil according to the present invention inhibits inflammatory cytokines in a concentration-dependent manner, and inhibits IL-8 at a level similar to that of indomethacin, a specialty drug.

[Test Example 2] Efficacy of natural fragrances for regulating sebum production

Human keratinocytes and human sebaceous gland cells were cultured in the same manner as in Test Example 1, treated with linoleic acid and arachidonic acid to produce sebum, and then treated with iso-tretinoin as a positive control and the fragrance oil of the present invention, respectively. did The treated cells were washed with refrigerated PBS solution, treated with a PBS solution in which 4% paraformaldehyde was dissolved at room temperature for 30 minutes, and placed at 4° C. overnight and fixed. 200 mg of Oil red O powder was diluted in 50 ml of isopropyl alcohol, purified with a 0.45 nm filter, and then 17 mL of purified water was added to prepare an oil red O solution. After removing the fixative from the cells and washing with PBS, 1 mL of the oil red O stain solution prepared above was treated and PBS washed 15 minutes later, and the oil red stained with triglycerides was imaged with an optical microscope. . To quantify the amount of sebum produced, cells were treated with isopropyl alcohol diluted with 4% NP-40 and stirred on a rocker for 3 minutes, then the solution was transferred to a 96-well plate and absorbance was measured at a wavelength of 520 nm. The results were organized as a ratio compared to the untreated group.

The analysis results are shown in FIG. 2 . Referring to FIG. 2 , it was confirmed that the perfume oil according to the present invention inhibited sebum production more effectively than isotretinoin, which is a prescription drug for acne suppression, and inhibited sebum production in a concentration-dependent manner.

[Test Example 3] Antibacterial activity test of natural fragrances

In order to evaluate the antibacterial activity of the natural fragrance in the present invention, the natural fragrance prepared in Preparation Examples 1 to 3 was applied to test the antibacterial activity against Malassezia globosa (ATCC 96807), which is a common bacterium on the scalp and causative agent of seborrheic scalp inflammation.

Using a yeast culture medium suitable for culturing Malassezia as a culture medium, cultured with shaking at 32°C for 2 days to culture Malassezia . A globosa test cell solution was prepared, and the test cell solution was diluted using a culture medium. A sample diluted solution for the antibacterial experiment was mixed with the culture medium at a concentration of 2.0% and prepared using the diluted solution.

200 μl of the sample dilution was placed in row 1 of the 96-well plate. In the remaining wells, 100 μl of each culture medium was added. After mixing the mixed solution in row 1 well, take 100 μl, put it in row 2, mix well, take 100 μl again and put it in row 3, and do double dilution. 10 μl of each test bacterial solution was added to all wells so as to be 10 ⁵ to 10 ⁶ . After culturing under the same conditions as the test bacteria culture conditions, the presence or absence of proliferation of bacteria was determined to the extent of suspension, and the minimum concentration without proliferation of bacteria was determined as the MIC value. If the mixed solution is opaque and it is difficult to determine whether or not the growth of bacteria is present, it was confirmed through microscopic observation. When the suspension is transparent to the same degree as the culture medium, it is determined as growth inhibition, and the growth inhibition of the test bacteria of Preparation Examples 1 to 3 is shown in Table 1 below.

MIC result ( - : growth inhibition / + : growth ) sample test bacteria sample concentration ( % ) 2.0 1.0 0.5 0.25 0.125 0.0625 0.03125 0.0156 0.005 Preparation Example 1 M. globosa - - - - + + + + + Preparation 2 M. globosa - - - - - + + + + Preparation 3 M. globosa - - - - - - + + +

The minimum growth inhibitory concentration was calculated based on the values measured above, and the results are shown in Table 2 below.

sample scalp Sang-Jae-Gyun Minimum stunting concentration MIC (%) Preparation Example 1 Malassezia globosa 0.25 Preparation 2 Malassezia globosa 0.125 Preparation 3 Malassezia globosa 0.0625

From the results of Table 2, it was confirmed that Preparation Examples 1 to 3 had antibacterial activity against Malassezia globosa bacteria that cause dandruff. A MIC of 0.25% or less can be said to have a significant antibacterial effect in the product.

[Examples 1-3 and Comparative Example 1] Preparation of scalp essence

A scalp essence was prepared according to the composition of Table 3 below using the above Preparation Examples 1 to 3 natural fragrance. More specifically, the natural fragrance of Preparation Examples 1 to 3, Polyoxyethylene Hydrogenated Castor Oils / POE (60) (Emalex HC-60, Nihon Emulsion Co., Ltd.), salicylic acid 0.2% , ethanol 10%, distilled water, ammonium acryloyl dimethyl taurate/vpicopolymer (manufacturer Aristoflex), and phenoxyethanol (Phenoxyethanol, PE) were used.

Ingredients (wt%) Example 1 Example 2 Example 3 Comparative Example 1 Polyoxyethylene Hydrogenated Castor Oil 0.5 0.5 0.5 0.5 Preparation Example 1 0.2 - - - Preparation 2 - 0.2 - - Preparation 3 - - 0.2 - Salicylic acid 0.2 0.2 0.2 0.2 Ethanol 10 10 10 10 Distilled water 88.3 88.3 88.3 88.3 Ammonium Acryloyl Dimethyl Taurate/Vpicopolymer 0.5 0.5 0.5 0.5 Phenoxyethanol 0.3 0.3 0.3 0.3

[Test Example 4] Skin irritation test

In order to check whether the skin is irritated when using the present invention, the scalp essence of Examples 1 to 3 and Comparative Example 1 prepared above was subjected to an evaluation group consisting of 37 men and women in their 20s and 30s, after washing the back skin, and then wiping off the moisture, It was made to stand by for 15 minutes in a constant temperature and humidity room (temperature 24 ± 4 °C, relative humidity 40 to 45%). An equal amount of scalp essence containing 0.20% of essential oil was applied to a cotton pad in an amount sufficient to prevent flow, and then attached to a selected location on the skin on the back. At 24 hours and 48 hours after the test substance was attached, the subject gave the level of stimulation from 0 to 4 (0 = no stimulation, 1 = very mild, 2 = weak, 3 = moderate, 4 = severe). (measured twice in total) and evaluated for irritation such as stinging and burning.

Table 4 shows the number of subjects who complained of stimulation according to the evaluation score for each time period.

Test substance name test concentration 24hr 48hr number of responses Judgment One 2 3 4 One 2 3 4 (n=37) Example 1 0.20% One - - - 0 - - - One no irritation Example 2 0.20% One - - - 0 - - - One no irritation Example 3 0.20% One - - - 0 - - - One no irritation Comparative Example 1 _ 0 - - - One - - - One no irritation

From the results of Table 4, it can be seen that Examples 1 to 3 containing the natural fragrance of the present invention did not cause skin irritation in the same manner as Comparative Example 1 which did not contain the natural fragrance.

Claims (6)

Sebum on the scalp, containing at least one natural fragrance selected from the group consisting of mandarin peel oil, gwanggwakhyang oil and pettigrain oil as an active ingredient, inhibits the proliferation of Malassezia globosa , a bacterium that causes seborrheic scalp inflammation control composition. The composition according to claim 1, wherein the amount of each of the natural fragrances is 0.001 to 5% by weight based on the total weight of the composition. The composition according to claim 1 or 2, wherein the composition relieves seborrheic scalp inflammation. delete delete The composition according to claim 1 or 2, wherein the composition inhibits the progression of scalp inflammation.

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