KR101196331B1 - Composition for skin care - Google Patents

Abstract

The present invention relates to a topical composition for improving or preventing skin diseases containing viridiflorol and improving atopic dermatitis and dry skin. It is possible to improve atopic dermatitis by inhibiting secondary bacterial infections and moisturizing the skin, and to restore the stratum corneum and skin barrier normally.

Description

External preparation composition for improving or preventing skin diseases {COMPOSITION FOR SKIN CARE}

The present invention relates to a topical skin composition that can improve atopic dermatitis and improve skin dryness. More specifically, the present invention is characterized in that it contains viridiflorol as an active ingredient and is effective in atopic dermatitis. The present invention relates to a topical composition for improving or preventing skin diseases that inhibits inflammatory reactions and secondary bacterial infections and alleviates atopic dermatitis by effective skin moisturizing action.

Atopic dermatitis is a dermatitis caused by various internal and external factors such as environmental pollution, an increase in allergens, and genetic factors. It is a chronic disease with dry skin, itching, inflammation, erythema and secondary bacterial infections. One of the skin diseases. Currently, atopic dermatitis includes steroids, immunosuppressants, and various antihistamines as therapeutic agents, but cosmetic compositions that can be used more safely and without skin irritation due to drug dependence and other side effects when these drugs are abused or misused, and The development of external skin preparations is being actively carried out.

Regarding the topical dermatitis composition which can be used for known atopic dermatitis, firstly, those which can play a role in skin moisturizing and barrier repair (eg, Korean Patent Registration No. 10-0374047) and secondly, skin itch relief and inflammatory response inhibitory compositions (eg Third, there is a secondary bacterial infection inhibiting composition (eg, Republic of Korea Patent Registration 10-0653012) Fourth antioxidant component and a cell active material (eg, Republic of Korea Patent Registration) and the like.

The present invention provides a new composition that inhibits the inflammatory reactions commonly occurring in atopic dermatitis and is effective for secondary bacterial infections and effectively moisturizes the skin. Effective for mitigating and improving

Viridiflorol used in the present invention is mainly used as a fragrance component and has been studied as an antimicrobial composition as known in the French patent (9213182). However, the new facts revealed by the present invention confirmed that the use of external preparations containing viridiflool showed a great effect in improving atopic dermatitis through not only simple moisturizing effect, but also anti-inflammatory, itching, and bacterial infection inhibition. And completed the present invention.

The present invention relates to an atopic dermatitis improving skin external preparation composition that inhibits inflammation and bacterial infections commonly seen in atopic dermatitis and is safer to the skin and allows the skin to recover normally without irritation. Epidermophyton, a bacterium involved in the secondary infection of atopic dermatitis, prevents skin hyperimmune reactions and exhibits anti-inflammatory action for this purpose. floccosum , Staphylococcus aureus , Pityrosporum The present invention provides a skin external preparation composition containing biriflolol, which is a composition that effectively inhibits ovale and effectively moisturizes the skin.

In order to achieve the above object, the external preparation composition for skin according to the present invention contains biridiflool and the biridiflool prevents the skin hyperimmune reaction and has anti-inflammatory action and inhibits secondary infection bacteria of atopic dermatitis. It is characterized by antibacterial activity and moisturizing by strengthening the skin's moisture retention ability.

In the external composition for improving or preventing skin diseases according to the present invention, the biridiflorol is contained in an amount of 0.0001% to 20% based on the total weight of the total external skin composition.

In the external preparation composition for skin containing bidiflolol according to the present invention, the external preparation composition is characterized in that all cosmetic compositions or pharmaceutical compositions that are commonly applied.

As described above, the topical dermatological composition containing viridiflool of the present invention has an anti-inflammatory effect of inhibiting an inflammatory response resulting from a hyperimmune reaction caused by atopic dermatitis, and antibacterial against secondary infection bacteria caused by inflammation. It is active, increases the water content in the skin, inhibits and improves erythema, redness, dry skin, itching, etc. It can be used as a cosmetic composition or external skin composition for preventing or improving the symptoms of dry skin and atopic dermatitis.

COX-2 inhibition measurement

The chemical name of biridiflool is decahydro-1,1,4,7-tetramethyl-1H-cyclopropazol-4-ol

(Decahydro-1,1,4,7-tetramethyl-1H-cycloprop (e) azulen-4-ol) is a plant-derived chemical having the structure shown in the following Chemical Formula 1. It is mainly extracted from plants such as Melaleuca viridiflora, juniPerus oxycedoras, AmozPha fructosa, Llimatadora baccata, and can also be obtained by chemical synthesis. Biridiflool is a yellowish substance with a sweet herb flavor and is mainly used in perfumes and fragrances for aromatic purposes.

Formula 1

The present invention inhibits skin inflammatory reactions and prevents secondary bacterial infections caused by atopy when applied to atopic skin by containing the above-mentioned viridiflorol as a main ingredient, while strengthening the moisturizing factor of the skin to increase the water content in the skin. Prevents or improves atopic dermatitis and skin dryness by increasing and keeping skin acidity low.

The external preparation composition for improving or preventing skin diseases according to the present invention may contain 0.0001 to 20% by weight of the biridiflorol, and more preferably 0.001 to 10.0% by weight, based on the total weight of the composition. At a concentration of 0.0001% by weight or less, no obvious effect could be expected, and at a concentration of 20.0% by weight or more, no apparent effect was increased with increasing content, and formulation suitability in general cosmetic compositions or external skin composition was also poor.

The external preparation composition for improving or preventing skin diseases according to the present invention contains a cosmetically or dermatologically acceptable medium or base. It is any formulation suitable for external application to the skin, for example emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) obtained by dispersing an oil phase in a solution, gel, solid or pasty anhydrous product, aqueous phase, and / or It may be provided in the form of a nonionic vesicle dispersant or in the form of a cream, skin, lotion, powder, ointment, spray or the like. These compositions may be prepared according to conventional methods in the art. In addition, the external preparation composition for improving or preventing skin diseases according to the present invention may be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The external preparation composition for improving or preventing skin diseases according to the present invention is a fatty substance, an organic solvent, a dissolving agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic type or Nonionic emulsifiers, fillers, metal-ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics It may contain adjuvants conventionally used in the cosmetic or dermatology field. These adjuvants are introduced in amounts commonly used in the cosmetic or dermatological field.

The composition for external application of water for improving or preventing skin disorders according to the present invention can be prepared in pharmaceutical compositions.

When the external preparation composition for improving or preventing skin diseases according to the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier, and these are usually lactose, dextrose, sucrose, sorbitol, Mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, Talc, magnesium stearate, mineral oil and the like, but are not limited thereto. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.

On the other hand, in order to increase the stability of the viridiprol when applying the viridiprol to the external formulations of the skin such as cosmetics, when using the nano liposomes using the equipment called Ultra Apex Mill formulation compatibility, temperature and oxidation It is more efficient because of stability.

Hereinafter, the present invention will be described in more detail with reference to Examples, Test Examples, and Preparation Examples. However, the following Examples, Test Examples and Preparation Examples are provided only for the purpose of illustration in order to help the understanding of the present invention is not limited to the scope and scope of the present invention.

Test Example 1: Bifidiflool atopic dermatitis related bacteria inhibition test

Epidermophyton to determine the inhibitory ability against the secondary infectious bacteria commonly observed in atopic dermatitis

Minimal inhibition concentrations of bacteria such as floccosum, Staphylococcus aureus, Staphylococcus epidermidis, and Pityrosporum ovale were measured.

Minimal Inhibitory Concentration (MIC) by Viridiflolol Staphylococcus aureus 0.05% Staphylococcus epidermidis 0.04% Epidermophyton floccosum 0.02% Pityrosporum ovale 0.02%

As shown in Table 1, biridiflorol was effectively observed to inhibit secondary infection strains occurring in atopic dermatitis even at low concentrations, and when used as a cosmetic composition of atopic dermatitis, it prevents the worsening of inflammation caused by bacterial infection. Can be.

Test Example 2 Anti-inflammatory Test of Biridiprol

As an effect of viridodilol, we examined the ability to inhibit the enzyme activity of COX (Cyclooxygenase) -2, an inflammatory-producing enzyme. The enzyme activity inhibition of COX (Cyclooxygenase) -2, an enzyme that produces prostaglandin, a substance that causes an acute inflammatory response, was determined by treating LPS (lipopolysaccharide) (THP-1) with human monocyte cell line THP-1. Viridiflorol was added at 0.03%, 0.06%, and 0.1% concentrations, and then incubated for 24 hours. After 24 hours, the cell medium was collected and the activity of COX-2 at each concentration was confirmed by measuring the amount of prostaglandin (Estaglandin) E2. As shown in Figure 1, it can be seen that biridiflorol effectively inhibits the production of PGE2 by COX-2, thereby confirming that it can be used in the inflammatory response occurring in atopic dermatitis.

Example 1 The preparation example of the flexible skin lotion (skin) in the external preparation composition for skin containing bidiflolol is as follows.

ingredient Content (unit: weight%) Viridiflorol 1.0 glycerin 6.0 1,3-butylene glycol 5.2 Fiji-800 1.0 Allantoin 0.1 DL-Panthenol 0.3 EDTA 0.02 Benzophenone-9 0.04 Sodium hyaluronate 5.0 ethanol 5.0 Octyldodeceth-5 0.2 Polysorbate 60 0.2 Preservative, fragrance, pigment Suitable amount Purified water Balance Sum 100

Example 2 The preparation example of the cream in the external composition for skin containing bidiflolol is as follows.

ingredient Content (unit: weight%) Viridiflorol 2.0 Wax 1.5 Stearic acid 1.5 Stearyl alcohol 2.2 Glyceryl stearate 2.0 Polysorbate 60 1.5 Sorbitan stearate 0.5 olive oil 1.1 Squalane 1.0 Mineral oil 7.0 Trioctanoine 5.0 Dimethicone 1.0 Sodium magnesium silicate 0.1 glycerin 5.0 Betaine 3.0 Triethanolamine 1.0 Sodium hyaluronate 4.0 Preservative, fragrance, pigment Suitable amount Purified water Balance

Test Example 3: Actual Clinical Trial-SCORAD Index Evaluation Method

7-30 years old using the example (cream formulation) and the control composition (the cream of which the other components were the same and the viridiflorol was replaced with water) of the composition containing the viridiprol prepared in Example 2 Korean Atopic Dermatitis Association (2005) One month for 20 patients with atopic dermatitis (10 in experimental group and 10 in control group) with at least two of the main findings and two or more of the findings according to Korean atopic dermatitis criteria An appropriate amount of liver lesion skin was used at least once daily for 8 weeks. For the efficacy evaluation method, the total scores for extent criteria, intensity criteria, and subjective symptoms are calculated by visually using the evaluation table as shown in FIG. 2 (SCORAD Index evaluation table) based on the clinical evaluation index of SCORAD. SCORAD Index was observed. In addition, as a mechanical evaluation method, the skin moisture (Skin Hydration) of the lesion was measured and used. Table 4 below is a SCORAD Index observation table according to the time course of the test group using an example of a composition containing a birifloflool in Example 2 and Table 5 is a SCORAD Index table of the control group.

Subject number Week 0 4 weeks 2 40.60 34.80 4 15.30 11.70 5 33.80 15.60 7 33.40 29.30 8 49.70 31.50 9 33.70 46.00 10 35.30 34.90 13 52.60 34.80 16 59.00 39.50 18 42.70 34.50 Average 39.61 31.26 Standard Deviation 12.36 10.36 p-value 0.030

Subject number Week 0 4 weeks One 25.70 45.10 3 15.60 11.90 6 15.30 15.30 11 31.50 30.30 12 71.10 46.90 14 40.90 35.60 15 27.40 19.30 17 28.20 17.70 19 57.30 38.30 20 38.70 27.50 Average 35.17 28.79 Standard Deviation 17.69 12.54 p-value 0.122

SCORAD INDEX is rated higher with more severe atopic symptoms. SCORAD INDEX decreased from 39.61 to 31.26 after 4 weeks and 21.81 after 8 weeks. The control group decreased from 35.17 to 28.79 after 4 weeks and 24.76 after 8 weeks. Statistically significant differences between the test group and the control group were found to be statistically significant at 4 weeks and 8 weeks after group A product use. The test group decreased by 17.80 and the control group decreased by 10.41 for 8 weeks. Based on this, it was determined that the test group was more effective in improving atopic dermatitis than the control group, and it was confirmed that the composition including the non-ridiflorol could be used as a clinically effective atopic skin external preparation.

Test Example 4 Measurement of Skin Hydration of Lesions

As in Test Example 3, the test group and the control group were divided to measure the water content of the atopic lesion. Corneometer CM825 (Courage + Khazaka electronic GmbH, Germany) was used for the measurement, and the results (Corneometer values) are shown in Table 6 (test group) and Table 7 (control group) below. In order to measure the skin moisture content, the constant temperature and humidity conditions of the measurement room were set at 22 ± 2 ℃ and 40 ~ 60% indoor humidity. When the test subject entered the skin diagnosis room, the patient was stabilized for 30 minutes to measure the temperature and humidity of the skin surface to adapt to the temperature and humidity of the space, and the water intake was limited for accurate evaluation. Skin measurement was performed three times before the test and after 4 and 8 weeks of testing. For the purpose of obtaining objective results, one researcher photographed the measurement site and indicated the location of the same site even after 4 or 8 weeks. It was possible to measure.

Subject number Week 0 4 weeks 8 parking 2 41.32 42.26 43.68 4 30.84 36.28 44.28 5 20.88 33.58 36.44 7 26.54 34.88 60.76 8 16.88 45.44 45.98 9 20.82 40.52 49.14 10 17.26 35.28 55.18 13 18.35 27.58 53.20 16 20.14 34.98 37.06 18 22.60 26.76 36.88 Average 23.56 35.76 46.66 Standard Deviation  7.57 5.906  8.42 p-value 0.001 0.000

Subject number Week 0 4 weeks 8 parking One 25.60 18.18 20.94 3 52.56 52.22 44.58 6 40.82 40.62 40.86 11 33.08 35.28 39.00 12 20.58 25.68 30.12 14 11.64 10.93 10.62 15 23.68 25.04 22.02 17 27.14 28.96 33.18 19 32.28 35.08 40.22 20 32.24 35.64 39.84 Average 29.96 30.76 32.14 Standard Deviation 11.25 11.71 11.05 p-value 0.447 0.282

As a result of this experiment, skin hydration increased from 23.56 to 35.76 after 4 weeks and 46.66 after 8 weeks. The control group also increased from 29.96 to 30.76 after 4 weeks and to 2.14 after 8 weeks. The difference was 23.10 in the test group and 2.18 in the control group. Statistical analysis with a significant difference of 5% showed that the skin moisture content (Skin Hydration) was increased significantly after 4 weeks and 8 weeks when using an example of a composition containing biridiprol. Therefore, it was confirmed that the test group according to the embodiment of the composition containing biridiprol has an atopic improvement effect at the lesion site than the control group.

There is no sign.

Claims (5)

An external preparation composition for improving or preventing skin diseases comprising biriflolol represented by Formula 1 as an active ingredient.
[Formula 1]

The method of claim 1,
The external preparation composition for improving or preventing the skin disease is an external preparation composition for improving or preventing skin diseases comprising the non-ridiflorol in an amount of 0.0001 to 20% by weight relative to the total weight of the external preparation composition for improving or preventing the skin disease. The method of claim 1,
The external preparation composition for improving or preventing skin diseases is glycerin, 1,3-butylene glycol, sodium hyaluronate, ethanol, stearyl alcohol, glyceryl stearate, trioctanoin, mineral oil, purified water and combinations thereof The external preparation composition for improving or preventing skin diseases that further comprises any one selected from the group consisting of. The method of claim 1,
The external preparation composition for improving or preventing the skin disease may include warning agents (PLASTERS), lotions (LOPTIONS), lining agents (LINIMENTS), liquids (LIQUIDS AND SOLUTIONS), aerosols (AEROSOLS), EXTERCTS, ointment ( OINTMENTS), FLUIDEXTRACTS, Emulsions (EMULSIONS), Suspensions (SUSPENSIONS), and Creams (CREAMS) of any one of the formulations selected from the group consisting of external composition for improving or preventing skin diseases. The method according to any one of claims 1 to 4,
In the external composition for improving or preventing skin diseases, the skin disease is a dry skin or atopic dermatitis, the external composition for improving or preventing skin diseases.

Images