Composition for improving skin comprising carnitine salicylate (CA-SA) as active ingredient

Abstract

The present invention relates to a cosmetic, pharmaceutical, and external pharmaceutical composition comprising carnitine salicylate (CA-SA) and magnolol as active ingredients, which can exhibit excellent efficacy in acne relief, sebum secretion relief, antibiosis, and skin sedation, and can be usefully used in the prevention, amelioration, or treatment of skin inflammatory diseases.

Description

Technical Field

[0001] The present invention relates to a skin-improving composition containing carnitine salicylate (CA-SA) as an active ingredient. Background Art

[0002] Acne is a common disease among teenagers, and about 85% of teenagers are affected by it. However, in some cases, acne can persist or recur even after adulthood.

[0003] Acne can be classified into non-inflammatory acne, i.e., comedones, and inflammatory acne, i.e., papules, pustules, and nodules. In particular, inflammatory acne can leave erythema pigmentation and acne scars, inducing physical and mental pain. Therefore, continuous research on the causes and treatment methods of acne is needed.

[0004] The main causes of acne include excessive sebum production, follicular keratosis and occlusion, acne bacteria (Propionibacterium acnes, C. acnes), and inflammation around the hair follicles. As treatment methods for acne, they usually include topical or systemic antibiotics and retinoids. Combined treatments can include chemical peeling, hormone therapy, and laser therapy.

[0005] However, these treatment methods are usually accompanied by side effects such as microbial resistance to antibiotics, stomatitis, skin irritation, and teratogenicity to retinoids. Therefore, the need to study acne treatment methods still exists.

[0006] Salicylic acid, known as β-hydroxy acid (βacid, BHA), is a metabolite of acetylsalicylic acid that exhibits analgesic and anti-rheumatic activities. Salicylic acid has been used in acne patients due to its bactericidal effect. However, if salicylic acid is used repeatedly, it can induce skin irritation and dryness. Therefore, it is recommended to use it in cosmetics at a concentration of 3.0% or less and at a pH of 3.5 or higher. In addition, when applied in an ionized form like salicylate under weak acidity, although skin irritation can be reduced, there are limitations in skin permeability and efficacy reduction. Therefore, it is difficult to feel high efficacy without skin irritation.

[0007] Recently, it has been found that if salicylic acid and carnitine form a eutectic mixture, it shows effects such as alleviating acne and promoting keratin exfoliation. (Patent Document 1) With the existence of this eutectic mixture being known, the fact is that research on a method that can exert more excellent effects on the skin using it is needed.

[0008] [Prior Art Documents]

[0009] [Patent Documents]

[0010] (Patent Document 1) Korean Patent Publication No. 2022-0126254 Summary of the Invention

[0011] Technical problem

[0012] Under the above background, the inventors of the present invention confirmed that when carnitine salicylate (CA-SA) and magnolol are used in combination, they have various skin improvement effects such as antibacterial, acne and inflammation alleviation, skin erythema recovery, and sebum secretion alleviation, and completed the present invention.

[0013] Accordingly, the present invention aims to provide a composition for improving skin, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

[0014] Technical solution

[0015] To solve the above problems, the present invention provides a cosmetic, pharmaceutical or quasi-pharmaceutical composition containing carnitine salicylate (CA-SA) and magnolol as active ingredients.

[0016] On the other hand, there is provided a method for improving skin or a method for preventing, improving or treating inflammatory skin diseases, which includes the step of treating the skin with a composition containing carnitine salicylate (CA-SA) and magnolol.

[0017] On the other hand, there is provided the use of carnitine salicylate (CA-SA) and magnolol in the preparation of a composition for improving skin or a composition for preventing, improving or treating inflammatory skin diseases.

[0018] The present invention will be described in detail below.

[0019] The present invention provides a cosmetic composition for improving skin, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

[0020] On the other hand, there is provided a method for improving skin, which includes the step of treating the skin with a cosmetic composition containing carnitine salicylate (CA-SA) and magnolol.

[0021] On the other hand, there is provided the use of carnitine salicylate (CA-SA) and magnolol in the preparation of a cosmetic composition for improving skin. In the present invention, the above carnitine is 4-trimethylamino-3-hydroxybutyric acid, and L-carnitine, DL-carnitine, their hydrochlorides and their derivatives can be used. Preferably, it can be L-carnitine.

[0022] In the present invention, carnitine salicylate (CA-SA) does not use salicylic acid in the form of a salt, but can be used by preparing a eutectic mixture in the form of carnitine salicylate (CA-SA) that ion-pairs with carnitine.

[0023] The above-mentioned eutectic mixture refers to a mixture of two or more solid or liquid substances, and refers to the mixing of two components with high melting points, so that the two components form a complex through dipole-dipole attraction, dipole-induced dipole attraction, intermolecular hydrogen bonding or van der Waals interactions between polar molecules. That is, the binding of the eutectic mixture refers to the intermolecular binding (formation of the eutectic mixture) formed while maintaining the individual inherent molecular structures based on the binding between dipoles caused by hydrogen bonds and partial charges of molecules.

[0024] In addition, the above-mentioned eutectic mixture can be formed by the binding of polar compounds to each other. The above-mentioned polar compounds can be polar molecules or charged molecules. In addition, there must be a difference in polarity between the above-mentioned polar compounds, and the same compounds cannot form a eutectic mixture.

[0025] The above-mentioned eutectic mixture can determine the ratio between the substances required for its eutectic mixture according to the charge of the molecules of the components forming the eutectic mixture, the types and numbers of functional groups of the molecules, and the polarity of the molecules or functional groups. In addition, the ratio between the substances required for its eutectic mixture can be determined according to the size or similarity of the molecules.

[0026] In the present invention, carnitine salicylate (CA-SA) can determine the ratio between the substances required for its eutectic mixture according to the charge and functional groups of carnitine and salicylate molecules, and the polarity of the molecules or functional groups. The above-mentioned carnitine salicylate (CA-SA) can be mixed in a molar ratio of carnitine:salicylate = 1 to 6:2, such as 6:2, 5:2, 4:2, 3:2, 2:2, 1:2, 5.5:2, 4.5:2, 3.5:2, 2.5:2, or 1.5:2. Carnitine and salicylate can form a eutectic mixture through the binding between dipoles caused by the partial charges of specific functional groups, and can form a eutectic mixture at the molar ratios within the above range through their chemical structures. When exceeding the above molar ratio, the low-temperature stability of carnitine decreases, salicylate cannot ion-pair with carnitine, and the remaining salicylate molecules may exceed the solubility in water and precipitate at low temperatures.

[0027] In the present invention, magnolol has a molecular weight of 266.33 and a molecular formula of C 18 H 18Lignin of O2 exists in the dry bark, root bark, etc. of plants in the Magnoliaceae family, namely Magnolia officinalis Rehd. Et Wils, and is known to have antibacterial, antifungal, and antioxidant activities.

[0028] As a result of evaluating the efficacy of combining carnitine salicylate (CA-SA) and honokiol both in vitro and in vivo, it was confirmed that excellent efficacy can be exerted in terms of antibacterial efficacy against acne bacteria, alleviation of sebum secretion, inhibition of the expression of inflammation-related factors, keratolytic efficacy, skin erythema recovery efficacy, and anti-acne activity effects. In particular, a significantly increased effect can be shown compared to when carnitine salicylate (CA-SA) and honokiol are treated alone.

[0029] In the present invention, by combining carnitine salicylate (CA-SA) and honokiol, an effect more improved than the original efficacy of each component can be shown. Specifically, compared to the individual use of carnitine salicylate (CA-SA) and honokiol, the enhancement rate of the effect brought about by the combined use can be 30% or more, 50% or more, 60% or more, 70% or more, 100% or more, 120% or more, 140% or more, 200% or more, 250% or more, 300% or more, 400% or more, 600% or more.

[0030] Although not limited thereto, in a specific example of the present invention, with respect to 100 parts by weight of the entire composition, the content of carnitine salicylate (CA-SA) can be 0.01 to 20 parts by weight, for example, 0.01 to 20 parts by weight, 0.02 to 20 parts by weight, 0.03 to 20 parts by weight, 0.05 to 20 parts by weight, 0.15 to 20 parts by weight, 0.2 to 20 parts by weight, 0.5 to 20 parts by weight, 1 to 20 parts by weight, 1.5 to 20 parts by weight, 0.01 to 10 parts by weight, 0.02 to 10 parts by weight, 0.03 to 10 parts by weight, 0.05 to 10 parts by weight, 0.15 to 10 parts by weight, 0.2 to 10 parts by weight, 0.5 to 10 parts by weight, 1 to 10 parts by weight, 1.5 to 10 parts by weight, 0.01 to 5 parts by weight, 0.02 to 5 parts by weight, 0.03 to 5 parts by weight, 0.05 to 5 parts by weight, 0.15 to 5 parts by weight, 0.2 to 5 parts by weight, 0.5 to 5 parts by weight, 1 to 5 parts by weight, 1.5 to 5 parts by weight, 0.01 to 1.5 parts by weight, 0.02 to 1 part by weight, 0.03 to 0.5 parts by weight, 0.05 to 0.2 parts by weight.

[0031] When the content of carnitine salicylate (CA-SA) of the present invention in the whole composition is less than 0.01 parts by weight, sufficient acne remission, inflammation remission and erythema remission effects cannot be expected. When the content exceeds 20 parts by weight, unwanted reactions such as allergies may occur or there may be problems with skin safety. Therefore, this is to prevent such problems.

[0032] In a specific example of the present invention, relative to 100 parts by weight of the whole composition, the content of magnolol can be 0.0000001 to 10 parts by weight, 0.000001 to 10 parts by weight, 0.0001 to 10 parts by weight, 0.0005 to 10 parts by weight, 0.001 to 10 parts by weight, 0.0000001 to 5 parts by weight, 0.000001 to 5 parts by weight, 0.0001 to 5 parts by weight, 0.0005 to 5 parts by weight, 0.001 to 5 parts by weight, 0.0000001 to 2 parts by weight, 0.000001 to 2 parts by weight, 0.0001 to 2 parts by weight, 0.0005 to 2 parts by weight, 0.001 to 2 parts by weight, 0.0000001 to 1 part by weight, 0.000001 to 1 part by weight, 0.0001 to 1 part by weight, 0.0005 to 1 part by weight, 0.001 to 1 part by weight, 0.0000001 to 0.5 part by weight, 0.000001 to 0.5 part by weight, 0.0001 to 0.5 part by weight, 0.0005 to 0.5 part by weight, 0.001 to 0.5 part by weight, 0.000001 to 0.001 part by weight, 0.0001 to 0.0005 part by weight.

[0033] When the content of magnolol of the present invention is less than 0.0000001 part by weight relative to 100 parts by weight of the whole composition, sufficient acne remission, inflammation remission and erythema remission effects cannot be expected. When the content exceeds 10 parts by weight, it may not be fully soluble in the composition.

[0034] In the present invention, honokiol can be included in the composition in the form of a plant extract containing honokiol, such as magnolia extract or houpo extract. As an example, bark extract of Magnolia kobus can be included. If honokiol is included in the form of a plant extract containing honokiol, the plant extract can be included in the composition in an amount capable of satisfying the above-mentioned honokiol content. For example, based on 100 parts by weight of the composition, the content of the plant extract containing honokiol can be 0.00001 to 10 parts by weight, 0.0001 to 10 parts by weight, 0.01 to 10 parts by weight, 0.05 to 10 parts by weight, 0.1 to 10 parts by weight, 0.00001 to 5 parts by weight, 0.0001 to 5 parts by weight, 0.01 to 5 parts by weight, 0.05 to 5 parts by weight, 0.1 to 5 parts by weight, 0.00001 to 2 parts by weight, 0.0001 to 2 parts by weight, 0.01 to 2 parts by weight, 0.05 to 2 parts by weight, 0.1 to 2 parts by weight, 0.00001 to 1 part by weight, 0.0001 to 1 part by weight, 0.01 to 1 part by weight, 0.05 to 1 part by weight, 0.1 to 1 part by weight, 0.00001 to 0.5 part by weight, 0.0001 to 0.5 part by weight, 0.01 to 0.5 part by weight, 0.05 to 0.5 part by weight, 0.1 to 0.5 part by weight, 0.0001 to 0.1 part by weight, 0.01 to 0.05 part by weight.

[0035] In a specific example of the present invention, the weight ratio of carnitine salicylate (CA-SA) to honokiol can be 500000 to 20:1. For example, it can be 500000 to 20:1, 300000 to 30:1, 5000 to 50:1, 3500 to 60:1, 2000 to 70:1, 500 to 100:1, 400 to 100:1, 300 to 100:1, 400 to 200:1, 300 to 200:1, 280 to 230:1, 250:1.

[0036] In the present invention, the above-mentioned skin improvement can be any one or more selected from the group consisting of acne alleviation, sebum secretion alleviation, skin sedation, antibacterial, skin erythema alleviation, acne inflammation improvement, and promotion of horny layer exfoliation.

[0037] In the present invention, "acne alleviation" can refer to inhibiting, impeding, or improving skin acne symptoms, and "acne inflammation improvement" can refer to inhibiting, alleviating, or improving the induction of inflammation caused by acne bacteria or acne symptoms.

[0038] In the present invention, "horny layer exfoliation" refers to the shedding, removal, or softening of the cutin accumulated in the horny layer of the skin from the horny layer of the skin.

[0039] In the present invention, "antibacterial" can refer to inhibiting, controlling, or preventing the growth or proliferation of bacteria, fungi, and other bacteria (such as acne bacteria) or microorganisms.

[0040] In the present invention, the cosmetic composition can be in the form of a general emulsifier and solubilizer. For example, it can have the following dosage forms: toners such as skin softening toners or nutritional toners, emulsions such as facial lotions and body lotions, creams such as nutritional creams, moisturizing creams, eye creams, essences, cosmetic ointments, balms, sprays, gels, facial masks, sunscreens, primers, liquid, solid or spray foundations, powders, makeup removers such as cleansing creams, cleansing lotions, cleansing oils, cleansing agents such as cleansing foams, soaps, shower gels, etc.

[0041] In addition, the above-mentioned cosmetics may additionally contain auxiliary agents commonly used in the field of cosmetics in the composition of the present invention, such as fatty substances, organic solvents, solubilizers, concentrators and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, metal ion blockers and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredients commonly used in cosmetics.

[0042] The above-mentioned cosmetic dosage forms may contain the above-mentioned composition of the present invention at a relatively high concentration for wash-off cosmetics such as makeup removers and cleansers whose active ingredients remain on the skin for a short period of time. On the other hand, for leave-on cosmetics such as lotions, emulsions, creams, and essences whose active ingredients remain on the skin for a long time, it is not a problem to contain the above-mentioned composition of the present invention at a lower concentration than for wash-off cosmetics.

[0043] Each of the above-mentioned components contained in the cosmetic composition of the present invention can be contained in the cosmetic composition of the present invention within a range not exceeding the maximum usage amount prescribed in the cosmetic safety regulations of each country.

[0044] The present invention also provides a pharmaceutical composition for preventing or treating inflammatory skin diseases, comprising carnitine salicylate (CA-SA) and magnolol as effective ingredients.

[0045] As another aspect, provided is a method for preventing or treating inflammatory skin diseases, comprising the step of administering a pharmaceutical composition comprising carnitine salicylate (CA-SA) and magnolol to a subject in need thereof.

[0046] As another aspect, provided is a use of carnitine salicylate (CA-SA) and magnolol in preparing a pharmaceutical composition for preventing or treating inflammatory skin diseases.

[0047] On the other hand, provided is the use of carnitine salicylate (CA-SA) and magnolol in the preparation of an acne treatment agent.

[0048] In the present invention, the inflammatory skin disease may be one or more selected from the group consisting of atopic dermatitis, seborrheic dermatitis, and acne skin, and more specifically, may be acne skin.

[0049] In the present invention, "prevention" refers to all acts of inhibiting or delaying a target symptom by administering the composition of the present invention.

[0050] In the present invention, "improvement" refers to all acts of making the target symptom better or favorably changed compared to the symptom before administration by administering the composition of the present invention.

[0051] In the present invention, "treatment" refers to all acts of relieving, alleviating, interrupting, or reversing a target symptom by administering the composition of the present invention.

[0052] The above "pharmaceutical composition" refers to a composition used for the purpose of diagnosing, treating, alleviating, managing, or preventing diseases in animals including humans.

[0053] The pharmaceutical composition of the present invention can be used alone, or in combination with other pharmaceutically active compounds showing preventive, improving, or therapeutic effects on aging, or in an appropriate combination.

[0054] The composition of the present invention can be administered in a pharmaceutically effective amount. The above pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment without causing side effects, and the effective dosage level can be determined according to factors including the health condition of the patient, the type of disease, severity, activity of the drug, sensitivity to the drug, administration method, administration time, administration route, excretion rate, treatment time, formulation, or drugs used concomitantly, and other factors well-known in the medical field. Specifically, it can be 0.1 mg / kg to 100,000 mg / kg per day, and more specifically 1 mg / kg to 10,000 mg / kg. For the administration of the above pharmaceutical composition of the present invention, it can be administered once a day or in multiple doses. Therefore, the above dosage does not limit the scope of the present invention in any way.

[0055] The above composition can be administered to mammals such as rats, mice, livestock, and humans through various routes such as parenteral and oral administration, and all modes of administration can be envisioned. For example, it can be administered by oral, rectal, or intravenous, intramuscular, subcutaneous, intrauterine dural, or intracerebroventricular (intracerebroventricular) injection.

[0056] The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, excipient, diluent, and / or adjunct according to its dosage form, method of use, and purpose of use.

[0057] In addition, the pharmaceutical composition of the present invention can be used alone or in combination with surgery, hormone therapy, drug therapy, and methods using biological response modifiers to improve, relieve, treat, or prevent inflammatory skin diseases.

[0058] The present invention also provides a pharmaceutical cosmeceutical composition for skin improvement or prevention or improvement of inflammatory skin diseases, comprising carnitine salicylate (CA-SA) and magnolol as active ingredients.

[0059] As another aspect, there is provided a method for improving skin or preventing or improving inflammatory skin diseases, which comprises the step of treating the skin with a pharmaceutical cosmeceutical composition comprising carnitine salicylate (CA-SA) and magnolol.

[0060] As another aspect, there is provided the use of carnitine salicylate (CA-SA) and magnolol in the preparation of a pharmaceutical cosmeceutical composition for skin improvement or prevention or improvement of inflammatory skin diseases.

[0061] "Pharmaceutical cosmeceutical" refers to an article having a milder action than a pharmaceutical among articles used for the purpose of diagnosing, treating, improving, alleviating, disposing of, or preventing diseases in humans or animals. For example, according to the Pharmaceutical Affairs Law, pharmaceutical cosmeceuticals exclude articles used for pharmaceutical purposes, and may be products for treating or preventing diseases in humans or animals, products having a mild or non-direct action on the human body, etc. For example, it may be selected from the group consisting of disinfectants, cleaning agents, kitchen cleaning agents, cleaning agents for cleaning, wet tissues, lotions, soaps, hand sanitizers, hair cleaning agents, hair conditioners, and ointments, but is not limited thereto.

[0062] In the present invention, the above-mentioned carnitine salicylate (CA-SA), magnolol, and skin improvement are as described in the cosmetic composition.

[0063] In the present invention, the methods of formulating pharmaceuticals and pharmaceutical cosmeceuticals, dosages, and additional ingredients can be appropriately selected from those in the art.

[0064] Advantages of the Invention

[0065] The composition of the present invention comprising carnitine salicylate (CA-SA) and magnolol can exhibit excellent effects in skin improvement aspects such as acne alleviation, sebum secretion alleviation, antibacterial, skin erythema alleviation, skin keratosis softening, and skin sedation, and can be usefully utilized in the prevention, improvement, or treatment of skin inflammatory diseases such as acne or atopy. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] Figure 1 It is an image for confirming the lipidogenesis inhibitory effect of Experimental Example 2.

[0067] Figure 2 It is a skin image of one of the volunteers for confirming the clinical evaluation of acne remission in Experimental Example 6.

[0068] Figure 3 It is a graph showing the results of confirming the clinical evaluation of acne remission in Experimental Example 6. DETAILED DESCRIPTION OF THE INVENTION

[0069] Hereinafter, the present invention will be described in detail through the following examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0070] EXAMPLE

[0071] In this experimental example, carnitine salicylate (CA-SA) prepared in Preparation Example 1 of Korean Patent Publication No. 10-2022-0126254 was used as the eutectic mixture of carnitine salicylate (CA-SA).

[0072] Experimental Example 1. Evaluation of Antibacterial Activity

[0073] The minimum inhibitory concentration (MIC) of carnitine salicylate (CA-SA) and honokiol against Propionibacterium acnes (C. acnes) was measured and compared with an antibiotic (clindamycin) and non-antibiotics (benzoyl peroxide and salicylic acid).

[0074] In an anaerobic environment (37 °C, 175 rpm), ribotype 5 (Strain HL043PA1) of Propionibacterium acnes (C. acnes) was cultured in reinforced clostridium broth medium (BD Diagnostics, Franklin Lakes, NJ). Thereafter, each sample was dissolved in water or DMSO, serially diluted 2-fold, and then 7.5 μL was added to 142.5 μL of a bacterial suspension at 7.5 x 10 5 CFU / ml and cultured for 72 hours. Thereafter, the turbidity (OD600) was measured (Synergy2 Multi-Mode Microplate Reader (BioTek Instrument, Winooski, VT)) to confirm the minimum inhibitory concentration that inhibits the growth of 90% or more of the bacteria. The results are shown in Table 1.

[0075] [Table 1]

[0076]

[0077] As shown in Table 1 above, when only carnitine salicylate (CA-SA) was treated, the MIC against Propionibacterium acnes (C. acnes) was 5,000 μg / ml. However, when carnitine salicylate (CA-SA) and magnolol were treated in combination, the MIC against Propionibacterium acnes (C. acnes) was 96 μg / ml. It can be seen that compared with the treatment of carnitine salicylate (CA-SA) alone, the antibacterial activity against Propionibacterium acnes (C. acnes) is more effective.

[0078] Experimental Example 2. Evaluation of sebum secretion alleviation

[0079] It was evaluated whether carnitine salicylate (CA-SA) and / or magnolol could regulate sebum secretion by inhibiting lipid production. It was confirmed that lipid production was effectively induced by testosterone treatment, and then the lipid production inhibitory effect was confirmed by treatment with carnitine salicylate (CA-SA), magnolol or a combination of the two components.

[0080] SZ95 cells, which are primary sebum cells, were cultured and maintained under humidified atmosphere containing 5% CO2 and 95% air at 37 °C. DMEM / Ham's F12 medium (Gibco) supplemented with 10% FBS and 5 ng / ml recombinant human epidermal growth factor (Invitrogen; Thermo Fisher, Waltham MA) was used as the medium. After the cells were nearly confluent (sub-confluent), they were collected using 0.05% trypsin-EDTA (Gibco) and subcultured, and the cells obtained by the second subculture were used.

[0081] The above cells were seeded at 1x10 5 cells per well in a 24-well plate (Greiner, Frickenhausen, Germany), and then cultured at 37 °C and 5% CO2 for 24 hours. Then, to stimulate lipid production, the cells were treated with 2x10 -8 M testosterone for 24 hours. After that, the cells were treated with 5 μg / ml carnitine salicylate (CA-SA) and / or 0.5 μg / ml magnolol or a vehicle (PBS) for 48 hours. The experimental group treated only with testosterone without treatment with carnitine salicylate (CA-SA) or magnolol was used as the positive control group. Cells treated only with the vehicle (PBS) without treatment with testosterone were additionally prepared as the negative control group.

[0082] To evaluate the amount of lipid production, SZ95 cells treated with the test sample were washed with PBS, and 4% formaldehyde was added for 5 minutes at room temperature to fix the cells. 100 μl of a 1 μg / ml Nile red (Sigma - Aldrich) solution diluted in PBS was added to each well for 15 minutes at room temperature to stain neutral lipids. The results are shown in Figure 1 in.

[0083] The well plate was covered with aluminum foil to block light, and fluorescence was measured at Ex / Em = 550 / 580 nm using a microplate reader (BioTek Instrument). And the percentage value of the absolute fluorescence units relative to the negative control group was used as the result value. Then, the reduction value of the test sample - treated group relative to the positive control group was calculated and shown in Table 2.

[0084] [Table 2]

[0085]

[0086] When carnitine salicylate (CA - SA) or honokiol was treated with testosterone - treated SZ95 cells, the lipid production amount decreased by 5.9% and 3.8%, with no significant difference. However, when carnitine salicylate (CA - SA) and honokiol were treated simultaneously, the lipid production amount increased by testosterone treatment decreased by 23.4%, indicating that the lipid production amount decreased significantly.

[0087] Experimental Example 3. Evaluation of the inhibition of the expression of inflammation - related factors MMP - 1 and VEGF

[0088] A cell line of human epidermal keratinocytes (HaCaT cells) was sub - cultured under humidified atmosphere containing 5% CO2 and 95% air at 37°C. The medium used was Dulbecco's Modified Eagels medium containing 10% fetal bovine serum (FBS, Gibco; Thermo Fisher, Waltham MA), penicillin (100 U / ml, Gibco), and streptomycin (100 μg / 100 μg / ml, Gibco). In addition, a lysate of Propionibacterium acnes (C. acnes) ribotype 5 (Strain HL043PA1) (1.36x 10 9 CFU / ml, OD = 1.7) was prepared as a Propionibacterium acnes (C. acnes) lysate. The Propionibacterium acnes (C. acnes) lysate was used to induce the expression of MMP - 1 and VEGF in HaCaT cells.

[0089] Then, as shown in Table 3, cultured HaCaT cells were treated with carnitine salicylate (CA-SA) and / or honokiol for 4 hours. Subsequently, a lysate of Propionibacterium acnes (C. acnes) and a culture medium were mixed at a mass ratio of 3:7, and the HaCaT cells were treated therewith for 30 minutes. The supernatant was collected, and the concentrations of MMP-1 and VEGF were measured by ELISA (R&D systems; Minneapolis, MN) using the manufacturer's protocol. Also, an experimental group without any treatment was used as a negative control group, and the percentage values of the MMP-1 and VEGF concentrations in each experimental group relative to the negative control group were used as the result values. An experimental group treated only with the lysate of Propionibacterium acnes (C. acnes) was set as a positive control group, and the reduction value of the sample-treated group relative to the positive control group was calculated and shown in Table 3.

[0090] To confirm the synergistic effect of carnitine salicylate (CA-SA) and honokiol, the following Colby's formula was used to compare the predicted value (Colby ratio) with the measured value, and the results are shown in Table 3.

[0091] Colby's formula: E = (A + B) - (A * B / 100), where E is the predicted value, A is the efficacy of active ingredient A, and B is the efficacy of active ingredient B. If the measured value is greater than the predicted value, it is determined that there is a synergistic effect.

[0092] [Table 3]

[0093]

[0094] As shown in Table 3, through the treatment with carnitine salicylate (CA-SA) and honokiol, the expressions of MMP-1 and VEGF were effectively inhibited, and compared with the case of using carnitine salicylate (CA-SA) and honokiol alone, significantly superior values were shown when used in combination, thereby confirming that a synergistic effect occurred. From these results, it can be known that the combined treatment with carnitine salicylate (CA-SA) and honokiol can effectively inhibit the expression of inflammation-related factors under the growth conditions of Propionibacterium acnes (C. acnes).

[0095] Experimental Example 4. Evaluation of the keratolytic effect

[0096] To evaluate the keratolytic effect of carnitine salicylate (CA-SA) and honokiol, tape stripping evaluation was performed on the stratum corneum (SC).

[0097] The application sites were pre-marked on the skin of the volunteers, and then 50 μl of a solution containing carnitine salicylate (CA-SA) and / or magnolol was applied at the concentrations shown in Table 4. After 3 hours, the skin surface was wiped to remove the residual substances. As a control group, a solution not containing the substance to be evaluated was used. A D-squame adhesive tape disk (CuDerm, Dallas, TX) was attached to the test site, and a pressure of 150 g / cm 2 was applied for 3 seconds using a cylindrical cone, and then the pressure was removed and the tape was peeled off from the skin. Three tape strips were obtained for each marked site.

[0098] The tape strips were collected into polystyrene petri dishes (ThermoFisher), and then, in order to perform quantitative keratolysis, 1 ml of 1 M NaOH was added to each petri dish and shaken for 2 hours. Then, 75 μl of the solution was transferred to three wells (96-well, Corning) and neutralized with an equal volume of 1 M HCl. 50 μl of Bradford assay reagent (Bio-Rad, Hercules, CA) was added to each well. After 15 minutes, using the empty well as the correction value, the optical density at 595 nm (OD 595nm) was measured, and the content of keratin was quantified using a γ globulin standard (Bio-Rad). The increase in the relative value (percentage) of the experimental group relative to the control group was used as the result value to compare the magnitude of the effect. The results are shown in Table 4.

[0099] [Table 4]

[0100]

[0101] As shown in Table 4, when only magnolol was treated, it was difficult to expect a keratin removal effect. However, when magnolol was treated together with carnitine salicylate (CA-SA), the keratin removal effect was significantly increased, and the value of the keratin improvement rate increased by 58.9% compared with the case of applying carnitine salicylate (CA-SA) alone.

[0102] From these results, it can be seen that the combined application of carnitine salicylate (CA-SA) and magnolol is more effective in promoting SC peeling than the individual application of carnitine salicylate (CA-SA) and magnolol.

[0103] Experimental Example 5. Evaluation of Skin Erythema Recovery by Inhibiting Erythema Induction

[0104] To evaluate the erythema recovery efficacy, nine volunteers aged between 25 and 35 years old were selected as subjects, and the erythema index was evaluated before erythema induction, after erythema induction, and 12 days after using the product. Erythema was induced by applying a 1% sodium dodecyl sulfate (SDS) dilution solution to the forearm for 24 hours, and a 5 wt% carnitine salicylate (CA-SA) emulsion, a 0.02 wt% honokiol emulsion, a 5 wt% carnitine salicylate (CA-SA) and 0.02 wt% honokiol emulsion, and an emulsion without carnitine salicylate (CA-SA) or honokiol (carrier) were repeatedly applied to the same area twice a day, morning and evening, for 12 days.

[0105] The erythema index was measured using a Mexameter (MX 18, Courage+Khazaka electronic GmbH, Germany). After calculating the erythema index recovery rate according to the following formula, the increase in the percentage value (relative recovery rate) of the erythema index recovery rate of each test sample emulsion coating group relative to the erythema index recovery rate of the carrier coating group was used to compare the effects. The results are shown in Table 5.

[0106]

[0107] (t: day of product use, -1: time point before erythema induction, 0: time point just after erythema induction)

[0108] To confirm the synergistic effect of carnitine salicylate (CA-SA) and honokiol, the predicted value (Colby ratio) and the measured value were compared using the same method as in Experimental Example 3, i.e., the Colby formula, and are shown in Table 5.

[0109] [Table 5]

[0110]

[0111] The erythema index recovery rate of the carnitine salicylate (CA-SA) coating group relative to the carrier coating group showed 23.5%, the honokiol coating group showed 16.2%, but the co-application group showed 36.7%. Compared with the individual use of carnitine salicylate (CA-SA) and honokiol, a significantly better value was shown when used in combination, thus confirming the occurrence of a synergistic effect.

[0112] Experimental Example 6. Clinical evaluation of anti-acne activity

[0113] Eight male and female subjects aged 19 - 38 years old (average 25 years old) with acne classified as grade 2 - 3 of IGA (Investigator's Global Assessment) and grade 1 or above of ISGA were randomly divided into two groups for evaluation.

[0114] In the morning and evening every day, apply an emulsion containing 5% by weight of carnitine salicylate (CA-SA) and 0.02% by weight of magnolol and a control carrier product without them. During this period, no other skin care products, ointments or drugs were used on the face. This was carried out for a total of 4 weeks, and evaluations were conducted 1 time on the starting day before product application and 1 time 4 weeks after product application, for a total of 2 times. During the evaluation, all subjects only washed the test site with warm water, and then, after resting for 20 minutes under certain lighting conditions, without air flow or direct light, and at a certain temperature and humidity (temperature 22 ± 2°C, humidity 50 ± 5%), participated in the evaluation test. The results are shown in Figure 2 and 3 .

[0115] As Figure 2 and 3 shown, compared with before product application, the group applying the emulsion containing 5% by weight of carnitine salicylate (CA-SA) and 0.02% by weight of magnolol showed further alleviation of acne symptoms, a significant reduction in the number of inflammatory acne lesions compared with the group applying the control carrier product, and it was confirmed to be particularly effective against papular and pustular acne.

[0116] Experimental Example 7. Sensory evaluation of anti-acne activity

[0117] Twenty acne patients were surveyed by questionnaire to see if they felt that their acne had improved after using the cosmetic containing the composition of the present invention for 4 weeks. The subjects continued to use their usual cosmetics, and additionally used the emulsion containing 5% by weight of carnitine salicylate (CA-SA) and 0.02% by weight of magnolol from Experimental Example 6 as the first step after washing their faces. The evaluation was scored on a 5-point scale (1: very deteriorated, 2: felt deteriorated, 3: no change felt, 4: felt improved, 5: improved a lot), and the results are shown in Table 6.

[0118] [Table 6]

[0119] Test Items Average Score Reduction in the Size of Pus and Papular Acne 3.7 Reduction in Whiteheads and Blackheads 3.8 Reduction in Inflammatory Sites Caused by Acne 3.8 Improved Sedation Rate of Inflammation Caused by Acne 4.0 Reduction in Sebum Secretion 3.7 Sedating the Skin by Improving Acne 3.8

[0120] As shown in Table 6 above, it was confirmed that when the cosmetic composition containing carnitine salicylate (CA-SA) and magnolol was repeatedly applied periodically, pustular and papular acne improved, the inflammatory sites caused by acne were alleviated and sedated, and sebum secretion decreased.

Claims

1. A cosmetic composition for skin improvement, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

2. The cosmetic composition for skin improvement according to claim 1, wherein, The content of the carnitine salicylate (CA-SA) is 0.01 to 20 parts by weight relative to 100 parts by weight of the whole composition.

3. The cosmetic composition for skin improvement according to claim 1, wherein, The content of the magnolol is 0.0000001 to 10 parts by weight relative to 100 parts by weight of the whole composition.

4. The cosmetic composition for skin improvement according to claim 1, wherein, The weight ratio of the carnitine salicylate (CA-SA) to the magnolol is 500000 to 20:

1.

5. The cosmetic composition for skin improvement according to claim 1, wherein The skin improvement is any one or more selected from the group consisting of acne alleviation, sebum secretion alleviation, skin sedation, antibacterial, skin erythema alleviation, acne inflammation improvement, and promotion of horny layer exfoliation.

6. A pharmaceutical composition for preventing or treating inflammatory skin diseases, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

7. The pharmaceutical composition for preventing or treating inflammatory skin diseases according to claim 6, wherein, The inflammatory skin diseases are one or more selected from the group consisting of atopic dermatitis, seborrheic dermatitis, and acne skin.

8. A pharmaceutical external composition for skin improvement, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

9. The pharmaceutical external preparation composition for skin improvement according to claim 8, wherein, The skin improvement is any one or more selected from the group consisting of acne alleviation, sebum secretion alleviation, skin sedation, antibacterial, skin erythema alleviation, acne inflammation improvement, and promotion of horny layer exfoliation.

10. A pharmaceutical external composition for preventing or improving inflammatory skin diseases, which contains carnitine salicylate (CA-SA) and magnolol as active ingredients.

11. The pharmaceutical external preparation composition for preventing or improving inflammatory skin diseases according to claim 10, wherein, The inflammatory skin diseases are one or more selected from the group consisting of atopic dermatitis, seborrheic dermatitis, and acne skin.

12. A method for improving skin, which includes the step of treating the skin with a composition containing carnitine salicylate (CA-SA) and magnolol.

13. A method for preventing or treating inflammatory skin diseases, which includes the step of administering to a subject in need thereof a composition containing carnitine salicylate (CA-SA) and magnolol.

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