KR102033089B1 - Compositions for decreasing sebum, skin desquamation and skin suppression - Google Patents

Abstract

The present invention is a complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; It relates to antimicrobial, anti-inflammatory, sebum reduction, exfoliation and skin soothing composition comprising a complex mixture of a mixture and niacinamide, the composition according to the invention inhibits the growth of acne disease-related microorganisms, sebum cells ( sebocytes) control the cleavage and sebum secretion, have keratin exfoliation action to improve the keratinization of hair follicles, as well as reducing the oil content, sebum secretion value, sebum secretion and number of open blemishes of acne skin. In addition, the composition comprising a complex mixture (AquMix) according to the present invention can be used safely in long-term use because there is little toxicity and side effects, and in particular can be safely applied to cosmetic or external skin composition. Particularly, it is water soluble and can be applied to the development of transparent properties such as transparent skin without solubilizer.

Description

Composition for antibacterial, anti-inflammatory, sebum reduction, exfoliation and soothing skin {Compositions for decreasing sebum, skin desquamation and skin suppression}

The present invention relates to a composition for antibacterial, anti-inflammatory, sebum reduction, exfoliation and skin soothing, more specifically a complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; And by containing a complex mixture of niacinamide (Niacinamide), it relates to a composition that is safe in human application and excellent in antibacterial, anti-inflammatory, sebum reduction, exfoliation and skin soothing effect.

Recently, the skin health of modern people is increasingly threatened by the problems of air pollution that has been severely increased due to the recent increase in dust and dust, the increase of the UV index, the tendency of hormonal abnormalities and external stress. As skin is frequently exposed to harmful substances such as chemicals and ultraviolet rays, sensitive skin types are increasing, and inflammatory reactions of skin cells are active due to immune response to stimuli, and the incidence of skin diseases such as acne and atopy is increasing.

Acne, which occurs mainly in puberty, gradually decreases after 30s, but the tendency that occurs in adults also increases year by year, and the degree tends to be remarkable. The cause of acne is not clear yet, but it is known that sebum secretion caused by male hormone is excessive, proliferation of causes of acne, such as propionibacterium acnes , and periphery inflammation of hair follicles, and hair follicle abnormalities. It has been reported that keratinization is the main cause, and it is due to the interaction of several factors such as genetic predisposition (Farrar MD, Ingham E Acne: Inflammation Clin Dermatol (2004) 22: 380-384).

One of the leading causes of acne is the proliferation of acne-causing bacteria propionibacterium acnes and propionibacterium granulosum . Excessive sebum secretion in the sebaceous glands or narrowing of the pores of the sebaceous glands causes clogging of the hair follicles, resulting in propioni , such as propionibacterium acnes and propionibacterium granulosum . Anaerobic bacteria in the bacterium increase the inflammatory response caused by bacteria as they change to a suitable environment for growth (Bowe WP, Shalita AR. Effective over the counter acne treatments, Semin Cutan Med Surg, 2008, 27: 170-176).

Most of the acne-producing bacteria are anaerobic bacteria that grow in a hair follicle, and propionibacterium acnes is known as the main cause. Other acne bacteria are found in acne patients. Propionibacterium granulosum and P. avidum . When inflammation occurs by such bacteria, aerobic bacteria such as Staphylococcus epidermidis and Staphylococcus aureus , which are located in the surrounding skin, expand the inflammatory response around the hair follicles. (Lim YS, Mung KB, Chung NE, Chung WS., A Study on the MIC of Antibiotics for Propionibacterium acnes in Patients with Acne, Kor J Dermatol 1995, 33: 437-444) .

In order to prevent the growth of such acne lesion-inducing bacteria or to suppress the inflammatory response caused by the bacteria, acne disease improvement research and clinical trials using antibiotics have also been conducted, but practical application is difficult due to the resistance to increasing antibiotics.

The proliferation of acne-associated bacteria around the hair follicles connected to the sebaceous gland and the resulting inflammatory response is another major cause of acne lesions that aggravate acne disease. Bacteria to multiply and lipase (lipase), an increasing number of induced secretion of inflammatory mediators secreted IL-1 α, IL-1 β, IL-8, the inflammatory response associated cytokines, such as TNF- α to stimulate peripheral immune cells and sebum cells The inflammatory response of skin cells around the hair follicles is accelerated and the skin becomes red and swollen.

The inflammatory response induced by propionibacterium acnes is known as the main mechanism of activation of the NF- κ B signaling pathway following Toll-like receptor (TLR) 2 activation. human monocytes) and propionyl sludge cake in keratinocytes (keratinocytes) tumefaciens arc Ness (P. acnes) was reported to increase the gene expression of inflammatory cytokines through transcription activation of NF- κ B (Nagy I, a Pivarcsi , Kis K et al., Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines / chemokines in human sebocytes.Microbes infect, 2006, 8: 2195-205, Zouboulid VV, Eady A, Philpott MLA et al., What is the pathogenesis of acne Exp Dermatol, 2005, 14: 143-52).

As inflammatory reactions accompany the progression of acne lesions as described above, the possibility of controlling inflammatory reactions by propionibacterium acnes for various anti-inflammatory plant extracts and compounds has been explored. Many studies on acne improvement are also underway (Chin Hsua, Tsung-Hsien Tsaib, You-Yi Li, Wen-Huey Wu, Ching-Jang Huang, Po-Jung Tsai., Wild bitter melon (Momordica charantia Linn.var) abbreviata Ser.) extract and its bioactive components suppress Propionibacterium acnes -induced inflammation, 2012, 135: 3 (1) 976-984).

In addition, the main etiology of acne disease is excess sebum secretion due to sebaceous gland irritation and thereby clogging pores. Excessly secreted sebum and clogged pores are prone to acne as an optimal environment for the growth of anaerobic and fat-friendly acne bacteria. However, there is no detailed information on the mechanisms that regulate sebum production or the death of sebum cells, so there is a need for treatment and treatment for acne improvement (Nelson AM, Gilliland KL, Cong Z et al., 13- cis Retinoic acid induces apoptosis and cell cycle arrest in human sebocytes, J Invest Dermatol, 2006, 126: 2178-89).

In the skin, the keratinization process occurs, where millions of aging keratinocytes break away from the skin and produce new keratinocytes every day. In general, keratinization is a phenomenon in which the keratinocytes produced by cell division in the basal layer of the epidermis move to the skin surface and react with proteolytic enzymes of the epidermal layer and naturally drop off from the skin. It is known that sebum and aging keratinocytes aggregate due to excessive secretion of sebum, which prevents the removal of keratinocytes and prevents hyperkeratinization (Titus S, Hodge J., Diagnosis and treatment of acne, Am). Farm Physician, 2012, 86 (8): 734-40). As keratinization progresses and the pores are blocked, keratin is accumulated, which causes the pores to expand and form a cotton cloth. This hyperkeratosis process is known to be another major cause of acne lesions, and studies for acne treatment are aimed at improving hyperkeratosis symptoms (Ganceviciene R, Fimmel S, Glass E, Zouboulis CC., Psoriasin and follicular hyperkeratinization). in acne comedones, Dermatology, 2006, 213 (3): 270-2).

Currently, acne treatments include retinoid preparations (tretinoin, adapalene), antibiotics (Clindamycin, erythromycin, etc.), benzyl peroxide, and azelaic acid (azelaic acid). (tetracyclin, doxycycline, minocycline), hormones (oral contraceptives, corticosteroids, spironolactone, cyproterone acetate), oral retinoids are used. However, topical treatments require long-term use, so side effects are concerned, and antibiotics have increased resistance to propionibacterium acnes , and oral retinoids have excellent therapeutic effects, but the skin and mucous membranes The use of the drug is restricted because it causes severe side effects such as dryness, lipid metabolism disorders, and fetal malformations.

For this reason, it is emphasized to develop a multi-functional substance that is safe from humans and improves skin diseases such as acne and is suitable for sensitive skin because it is derived from natural products and has fewer side effects.

On the other hand, in recent years, natural antibiotics obtained from natural resources or microbial resources, natural ingredients that have an effect of exfoliation and astringent are also being studied and are currently applied as cosmetic ingredients. Generally, the soothing ingredients applied to the product include useful ingredients such as alpha-bisabolol and stearyl glycyrrhizinate, and recently, essential oils such as myrtle and chamomile are used as natural materials. Has been studied. However, most of the natural soothing ingredients are useful, and there is a limit that they are suitable for emulsified type products rather than being applied to solubilized type formulations such as skins and toners. It can be commercialized as a solubilization type, but the content of solubilizers, etc. increases, there is a fear that it may be irritating to sensitive acne skin, and essential oils may give some people a sense of rejection due to strong odor. Therefore, it is important to develop water-soluble sedative ingredients that have no effect on acne skin as well as improving acne.

The present inventors have antibacterial, anti-inflammatory, sebum reduction, exfoliation and soothing effects on acne-causing bacteria using natural plant extracts and niacinamide at the same time, high stability and safety, no skin side effects, sensitive acne skin The present invention has been completed by developing a water-soluble composite material suitable for use.

Therefore, the technical problem to be solved in the present invention is to provide a composition for antimicrobial, anti-inflammatory, sebum reduction, exfoliation and skin soothing comprising a complex mixture of natural extracts and niacinamide as an active ingredient.

In one embodiment the present invention is a complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; It provides a composition for antibacterial, anti-inflammatory, sebum reduction and skin soothing comprising a complex mixture of and niacinamide as an active ingredient.

In the present invention, Citrus Unshiu Peel is a fruit peel of Citrus unshiu , and has been widely used for medicinal purposes since it is called tangerine peel, dermis, tangerine peel, green peel and stirrup. Citrus trees are evergreen trees of the genus Uncense and Citrus, native to Jeju Island in Korea, and are known to be distributed in Japan, China, Latin America, and the Black Sea. "Citrus" is a fruit of natural, hybrid or mutant citrus (Citrus), an alkaline food high in vitamin C. It is good for skin care, fatigue recovery and calcium absorption. Citrus fruits are rich in vitamins B1, B2 and various organic acids, as well as limonoids and blood vessels that are known to be effective in anticancer effects, as well as liver detoxification, anticancer, anti-inflammatory and antibacterial effects. Hesperidine is known to be rich.

In the present invention, the onion ( Allium Cepa Bulb) is a perennial plant belonging to the genus Liliales leek ( Allianeae ) allium ( Allium ) perennial plant anticancer effect, antibacterial effect, heavy metal detoxification effect, tyrosinase (tyrosinase) inhibitory activity, lipid Biological activity effects on oxide inhibition and antioxidant effects have been reported. Flavonoids contained in onions have recently attracted attention as bioactive substances having various beneficial functions for humans.

In the present invention, Lycii fructus is a fruit of Lycium chinense Miller , which is a deciduous shrub belonging to the branch family, and is known to be effective in nourishing, tonic, blood, jigger, and corrector in synergism. Wolfberry contains a large amount of functional ingredients such as betaine and rutin, has a dihydrotestosterone (DHT) content and activity inhibitory effect, which acts as a powerful androgen hormone. Preventive, detoxifying action. It has been known to enhance immune function, improve liver function, and lower blood cholesterol. Its ingredients are goji berries, and the fruit contains carotenoids, cholin, meliscic acid, zeaxanthin, and pisal. It is known to contain a large amount of physalien, betaine, β-sitosterol, vitamin B1 and unsaturated fatty acids.

In the present invention, licorice ( Glycyrrhiza Glabra Root) is a plant distributed in northeastern China, Siberia, Mongolia and the like, and is widely used as a medicine in the East and West. Licorice root extract contains ingredients such as glycyrrhizin, saponins, asparagine, sugars, and resins.

In the present invention, white willow leaf (Salix Alba Willow Leaf) is superior to the pain relief effect of a leaf of the white willow distributed in the US North and Central Asia and Western Europe (Salix Alba Willow), malaria healing agent is also the use .

In the present invention, spina (Spinacia oleracea ) is a year-old or biennial grass belonging to the family of perennial, and contains organic acid (oxalic acid), malic acid, citric acid, iodine (oxo) and vitamin C. It also contains vitamin B1, vitamin B2, niacin, folic acid, saponin, and nutrients such as sugar, protein, fat, fiber, calcium and iron.

In the present invention, hydrolyzed rice bran (Hydrolyzed Rice Bran) is a hydrolyzate of rice bran extract is obtained by hydrolysis by acid, enzyme or conventional methods. Rice bran contains nutrients such as vitamin B1, vitamin B2, lipids, carbohydrates and minerals.

In the present invention, niacinamide is a kind of niacin, which is a vitamin B group, and is a water-soluble vitamin B3, also known as nicotinamide. Niacinamide, together with ceramide, promotes the synthesis of cholesterol and fatty acids necessary for the formation of lamellar structures, thereby reducing the loss of water in the epidermis and improving lipid content.

In the present invention, "composite extract" refers to a tangerine peel, onion, wolfberry, licorice, white willow leaves and spinach mixed and extracted from the extract or extracts of these extracts.

In addition, the complex extract is a mixture of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach all extracts, fractions, purified products obtained in each step of extraction, fractionation or purification (separation, fraction) Diluent, concentrate, dry matter or any form formulated using the same.

In addition, the complex extract is all extracts, fractions, purified products, dilutions thereof obtained at each step of extracting, fractionating, or purifying (separation, fraction) each of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach, Refers to a mixture of concentrates, dry matter or all forms formulated using the same.

The complex extract may be obtained using an extraction method and an extraction solvent known in the art. The extraction solvent is water, methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) , 1,3-butylene glycol, propylene glycol or a mixed solvent thereof, the active ingredient of the complex extract can be extracted at room temperature or warmed under conditions that are not destroyed or minimized. Depending on the extraction solvent to be extracted, the degree of extraction and loss of the active ingredient of the complex extract may vary, so select an appropriate extraction solvent. The extraction method is not particularly limited, and for example, cold needle extraction, ultrasonic extraction, reflux cooling extraction and the like can be used.

In addition, the complex extract can be obtained through a conventional purification process in addition to the extraction by the extraction solvent. For example, through various purification processes in which ultrafiltration having a constant molecular weight cut-off value, cryofiltration, centrifugation, separation by various chromatography (chromatography according to size, charge, hydrophobicity or affinity) are additionally performed. It can also be obtained through the obtained fraction, but is not limited thereto.

In one specific embodiment of the present invention, tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach extract is 20 to 35 ℃ each of tangerine peel, onion, rice bran, wolfberry, licorice, white willow leaf and spinach It can be obtained by drying with ultrasonic wave, followed by pulverization and immersion in ethanol.

In one specific embodiment of the present invention, the tangerine peel extract can be obtained by pulverizing and juice the raw mandarin peel sample.

In the present invention, "rice bran hydrolyzate" is prepared by extracting from the rice bran as in the complex extract and then hydrolyzed it.

In one specific embodiment of the present invention, the rice bran hydrolyzate may be obtained by drying rice bran at 20 to 35 ° C., then crushing and soaking in ethanol for ultrasonic extraction followed by hydrolysis using an enzyme.

"Compound mixture" of the present invention is called "AquMix" in the present invention, the complex extract of the tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; And niacinamide; are prepared by mixing as appropriate. Each component of the complex mixture is based on 100 parts by weight of tangerine peel extract, 800 to 1,000 parts by weight of onion extract, 800 to 1,000 parts by weight of wolfberry extract, 100 to 200 parts by weight licorice extract, 100 to 200 parts by weight of white willow leaf extract And 20 to 40 parts by weight of spinach extract, 100 to 200 parts by weight of rice bran hydrolyzate, and 800 to 1,000 parts by weight of niacinamide. Preferably, based on 100 parts by weight of tangerine peel extract, 900 to 1,000 parts by weight of onion extract, 900 to 1,000 parts by weight of goji berry extract, 100 to 160 parts by weight licorice extract, 100 to 160 parts by weight of white willow leaf extract and spinach extract 30 To 40 parts by weight, 100 to 160 parts by weight of rice bran hydrolyzate, and 900 to 1,000 parts by weight of niacinamide. More preferably, based on 100 parts by weight of the tangerine peel extract, 900 to 960 parts by weight of onion extract, 900 to 960 parts by weight of goji extract, licorice extract 110 to 150 parts by weight, white willow leaf extract 110 to 150 parts by weight and spinach extract 30 to 36 parts by weight, rice bran hydrolyzate 110 to 150 parts by weight, niacinamide 900 to 960 parts by weight of the mixture. When it is out of the content range, sebum reduction, exfoliation and skin soothing effect of the composition according to the present invention are reduced.

As one specific example, the complex mixture was mixed in the amounts shown in Table 2.

In the present invention, "antibacterial" refers to the action of inhibiting or controlling the growth and proliferation of microorganisms such as bacteria and fungi, and preferably means the action of inhibiting or controlling the growth and proliferation of dermatophytes.

In the present invention, "anti-inflammatory" benefits the suppression of inflammation formed by the invasion of external infectious agents (bacteria, fungi, viruses, various types of allergens), delayed onset of inflammation, improvement of the inflammatory state or inflammatory state It means any action that changes.

In the present invention, "sebum reduction" is to inhibit or control sebocyte differentiation and to inhibit or treat oily skin, but is not limited thereto, acne, seborrheic dermatitis, perioral dermatitis, red nose, blackhead Or reduction, alleviation, or treatment of blemishes and the like.

In the present invention, "exfoliation" refers to restoring the regeneration cycle of the blocked skin by removing the aging keratin, to pull fresh cells generated under the stratum corneum upward to maintain a clear and clean skin.

In the present invention, "skin soothing" means giving a cool, refreshing or cold feeling to the skin.

In one specific embodiment, the antimicrobial, anti-inflammatory, sebum reduction, exfoliation and skin soothing composition of the present invention can be used as a cosmetic composition.

The cosmetic composition of the present invention comprises the complex mixture (AquMix) in an amount of 0.0001 to 20% by weight, preferably 0.001 to 10% by weight, more preferably 0.01 to 3% by weight, based on the total weight of the cosmetic composition. do. If the amount is less than 0.0001% by weight of acne skin improvement effect is weak, when the amount exceeds 20% by weight is very small increase in the effect of the increase in the content is economical and difficult to prepare a formulation.

The cosmetic composition may further include components commonly used in cosmetic compositions in addition to the complex mixture (AquMix). For example, it may include conventional auxiliaries and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and agents.

The cosmetic composition may be prepared in any formulation commonly prepared in the art. For example, it may be formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation or spray, and the like. More specifically, it may be prepared in a formulation such as nourishing cream, astringent lotion, flexible lotion, lotion, essence, nourishing gel or massage cream. However, it is not particularly limited to this.

When the formulation of the cosmetic composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier components. Can be.

When the formulation of the cosmetic composition is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, and in the case of a spray, additionally chlorofluorohydrocarbon, Propellant such as propane / butane or dimethyl ether.

When the formulation of the cosmetic composition is a solution or emulsion, a solvent, a solubilizer or an emulsifier may be used as a carrier component. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester can be used. have.

When the formulation of the cosmetic composition is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester as a carrier component, Crystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the cosmetic composition is a surfactant-containing cleansing agent, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid. Amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition of the present invention exhibits excellent sebum reduction, exfoliation and skin soothing effect without cytotoxicity.

In another specific embodiment, the antimicrobial, anti-inflammatory, sebum reduction, exfoliation and skin soothing composition of the present invention can be used as a pharmaceutical composition.

The pharmaceutical composition of the present invention is an amount of 0.0001 to 50% by weight, preferably 0.001 to 30% by weight, more preferably 0.01 to 20% by weight of the complex mixture (AquMix) based on the total weight of the pharmaceutical composition Include as. If the amount is less than 0.0001% by weight, the effect of improving acne skin is weak, and when the amount exceeds 50% by weight, the increase in effect due to the increase of the content is very weak, and it is difficult to manufacture the formulation.

The pharmaceutical compositions of the present invention may be prepared in unit dosage form or in multidose form by formulating with a pharmaceutically acceptable carrier and / or excipient, according to methods which can be easily carried out by those skilled in the art. It may be prepared by incorporation into a container. In this case, the formulation may be in the form of a solution, suspension, syrup or emulsion in an oil or an aqueous medium, or may be in the form of an exir, powder, powder, granule, tablet or capsule, and may further include a dispersing or stabilizing agent.

Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are commonly used in the preparation of pharmaceutical compositions, and include carbohydrate compounds (eg, lactose, amylose, dextrose, sucrose, sorbitol, mannitol, starch). , Cellulose, etc.), acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, salt solutions, alcohols, gum arabic, vegetable oils (e.g. corn Oils, cotton seed oil, soy milk, olive oil, coconut oil), polyethylene glycol, methyl cellulose, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil, and the like.

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. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical compositions of the present invention can be used in the form of injections or external preparations according to conventional methods.

The pharmaceutical composition of the present invention has a sebum reduction and skin soothing effect, and the administration method includes administering the pharmaceutical composition in a pharmaceutically effective amount to mammals such as rats, mice, livestock, humans, etc. in various routes.

The pharmaceutical composition may be administered orally or parenterally, and is preferably applied by topical application by parenteral administration, more preferably by application.

Suitable dosages of the pharmaceutical compositions of the present invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be. The dosage of the pharmaceutical composition of the present invention is in the range of 0.001-100 mg / kg on an adult basis. In addition, in the case of external preparations, it is recommended to continue the application for 1 month to 5 times a day in an amount of 1.0 to 3.0 ml on an adult basis. However, the dosage does not limit the scope of the present invention.

According to one specific embodiment of the present invention, the pharmaceutical composition according to the present invention inhibits or eliminates the proliferation of dermatophytes, inhibits, eliminates or ameliorates the inflammation caused by the bacteria or sebum, or produces sebum. It can be applied to various sebum-related diseases, diseases or abnormal conditions that can be prevented or treated by inhibiting or eliminating it. Sebum-related diseases that can be prevented or treated include, but are not limited to, acne, seborrheic dermatitis, perioral dermatitis, red nose, blackheads and spots.

According to one specific embodiment of the present invention, when the external preparation for skin containing the complex mixture is patched on acne skin for 4 weeks, the oil content is 26 to 51% compared to when the external preparation for skin is not included in the complex mixture. Blocks sebum secretion, inhibits sebum secretion by 4 to 31%, significantly reduces the number of cotton cloths by 20 to 26%, and satisfies the fact that more than 90% of subjects are moist due to the overall feeling of use and suitability for acne skin use. Was rated above normal.

The composition containing the complex mixture (AquMix) according to the present invention controls the division and sebum secretion of sebum cells, inhibit the growth of microorganisms related to acne disease, oil content, sebum secretion value, sebum secretion and opening of acne skin It has the effect of reducing the number of cotton cloths.

According to one specific embodiment of the present invention, the results of cytotoxicity and skin irritation test against tangerine peel, onion, hydrolyzed rice bran, wolfberry, licorice, white willow leaf and spinach complex extract, rice bran hydrolyzate and niacinamide It has been found to be cytotoxic to keratinocytes and harmless to humans.

Therefore, the tangerine peel, onion, hydrolyzed rice bran, goji berry, licorice, white willow leaf and spinach extract of the present invention (AquMix) has little toxicity and side effects, so it can be used safely for a long time. , In particular in cosmetics and pharmaceutical compositions.

As such, the complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaves and spinach according to the present invention; The composition comprising a complex mixture of rice bran hydrolysate; and niacinamide (AquMix) as an active ingredient has an antibacterial and anti-inflammatory effect to inhibit the growth of acne-related microorganisms, and to prevent sebocyte division and sebum secretion It not only has a keratin exfoliating effect that regulates and improves the exfoliation of hair follicles, but also reduces the oil content, sebum secretion value, sebum secretion, and the number of open blemishes of acne skin. In addition, it reduces the degree of translocation of NF-kB and increases the amount of moisturizing change of the skin, thus exhibiting a soothing effect. The composition comprising the complex mixture (AquMix) according to the present invention has little toxicity and side effects, so it can be used safely even in long-term use, and in particular, it can be safely applied to cosmetics and pharmaceutical compositions.

1 shows a flow chart of one specific preparation of the composition of the present invention.
2 is a graph showing the anti-inflammatory effect of the composition of the present invention.
3 is a graph showing the oil content over time when using the external preparation for skin containing the composition of the present invention.
Figure 4 is a graph showing the oil content change rate over time when using the external preparation for skin containing the composition of the present invention.
Figure 5 is a graph showing the sebum measurement value over time when using the external preparation for skin containing the composition of the present invention.
Figure 6 is a graph showing the rate of sebum change over time when using an external preparation for skin containing the composition of the present invention.

Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

Example 1 Selection of natural extract material and establishment of composition ratio

1-1. Preparation of Natural Extracts

Each natural product shown in Table 1 onion (outpost), red tree (leaf), wolfberry (fruit), licorice (outpost), loquat (leaves), rice bran (shell), white willow (shell), bird vine (outpost) ), Buckwheat (flower), spinach (ground), moon julan (outpost), oyster tree (leaves), tangerine (shell), and vast greens (ground) after washing thoroughly to remove foreign substances and impurities, 20 ~ 35 ℃ After drying in the dry state, the particle size was pulverized to 1 mm or less.

100 g of each powder obtained was immersed in 10 L of 70% ethanol, and ultrasonically extracted twice for 24 hours. Then, the obtained extract was filtered through filter paper (Advantes, No. 2) and concentrated under reduced pressure to prepare each extract. Rice bran was prepared by extracting in the same manner as described above, and then hydrolyzed using an enzyme, filtered again on filter paper (Advantes, No. 2), and concentrated under reduced pressure to prepare a rice bran hydrolyzate.

1-2. Antibacterial effect verification

By treating the above-described embodiment 1-1-related acne bacterium Propionibacterium sludge bacterium of the extract obtained in the arc Solarium Ness bacterial growth culture medium and extract the appropriate OD values to test the antimicrobial activity of the (P. acnes) at different concentrations acne related bacteria The antimicrobial activity against these was measured. Viability of acne bacteria was observed using alamar blue staining. The results are shown in Table 1 below.

1-3. Sebum cell differentiation inhibitory effect test

In order to investigate the effects of the extract prepared in Example 1-1 on sebaceous cell differentiation, insulin (20 nM), which induces sebocyte differentiation, was treated and simultaneously treated with the extract, followed by incubation for a period of time. After the treatment, fat was stained with a nile red reagent that stains intracellular fat in red, and cell numbers stained with FACS were checked. As a result, it was confirmed that the fat staining was noticeably increased in the insulin treated group compared to the negative control group which did not process anything, and the fat differentiation was normally performed. The results were shown in Table 1 below.

1-4. Exfoliation effect verification

In order to confirm the exfoliation efficacy of the extract prepared in Example 1-1, the skin using 5% DHA (Dihydroxyacetone) targeting 15 subjects who have no other medical history and are suitable for the exfoliation test through skin condition diagnosis After dyeing, the exfoliation effect was measured by the skin color change due to skin exfoliation. Tanning the skin by applying the DHA solution twice a day, and then adding the control substance (Control skin formulation) and the test substance (skin formulation containing 0.02% extract) to the same area twice a day for 10 days Apply evenly. Skin markers marked the areas where the control and test materials were applied and the areas where the test materials were not applied (Non treat). The skin color measurement device (Corneometer, CK electronic, German) was used to measure the degree of discoloration of keratin by comparing the color difference daily, and the results are shown in Table 1 below.

Human keratin exfoliation change rate (%) was calculated according to the following equation (1).

Natural name
(Extraction area) Antimicrobial effect
( P. acnes ) Sebocyte Differentiation Inhibition (SEB-1) Exfoliation
effect Selected Onion (Outpost) +++ ++++ - ○ Rhododendron (leaves) － - + Wolfberry (fruit) ++++ + － ○ Licorice (Outpost) +++ ++++ - ○ Loquat (leaves) － - + Rice bran
Hydrolyzate +++ ++++ - ○ White willow (leaves) + + +++ ○ Bird Vine (Outpost) － - + Buckwheat (flowers) － + + Spinach (ground part) + + +++ ○ Moonjuran (outpost) － + - Oyster tree (leaves) + － － Tangerine (peel) － + ++++ ○ Wild herbs
(Ground part) + － - -: No effect, +: weak effect, ++: moderate effect, +++: strong effect, ++++: very strong effect

A total of 14 plant extracts were tested for antibacterial, sebum production, and skin peeling of acne bacteria. Seven degradation products were selected as an active ingredient of the composition.

Example 2 Preparation of Complex Mixture According to the Present Invention

Through the composite composition of the selected extract and niacinamide, it was verified whether the combination function for the skin soothing action and the synergy of the efficacy could be shown. Specifically, a complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; Niacinamide was mixed in the ratio of Table 2 to prepare a complex mixture (AquMix) according to the manufacturing process shown in FIG. The complex mixture is named AquMix for convenience.

Composite Mix (AquMix) Composition Content (g) Citrus Unshiu Peel Extract Tangerine Peel Extract 0.3 Allium Cepa (Onion) Bulb Extract Onion extract 2.8 Hydrolyzed rice bran Extract Hydrolyzed Rice Bran Extract 0.4 Lycium Chinense Fruit Extract Wolfberry extract 2.8 Glycyrrhiza Glabra (Licorice) Root Extract Licorice extract 0.4 Salix Alba (Willow) Leaf Extract White Willow Leaf Extract 0.4 Spinacia Oleracea (Spinach) Leaf Extract Spinach Extract 0.1 Niacinamide Niacinamide 2.8

<Test Example 1> Antibacterial, sebum production inhibition and exfoliation effect measurement

Antibacterial, sebum production inhibition and exfoliation effect of the composite mixture (AquMix) prepared according to Example 2 was measured by the same method as 1-2, 1-3, 1-4 of Example 1 above. The measurement results are shown in Table 3 below.

Compound Mixture Name Antimicrobial effect
( P.acnes ) Sebocyte Differentiation Inhibition (SEB-1) Exfoliation effect Aqumix ++++ ++++ +++ -: No effect, +: weak effect, ++: moderate effect, +++: strong effect, ++++: very strong effect

As a result, the composite mixture (AquMix) according to the present invention was shown to have excellent antimicrobial activity, sebum production inhibitory effect and exfoliation effect against P. acne bacteria.

Test Example 2 Anti-inflammatory Effect Measurement

In order to measure the anti-inflammatory effect of the complex mixture (AquMix) of Example 2, NF-κB luciferase activity and the production of inflammatory cytokines were measured.

Specifically, transient transfection of NF-κB luciferase reporter plasmid into keratinocytes using a transfection reagent, followed by microbial toxin Treatment of lipopolysaccharide (LPS) activates the NF-κB promoter (promoter) to promote the production of inflammatory cytokines such as IL-8 and TNF-α, which cause inflammation. Therefore, substances capable of inhibiting the activity of the NF-κB promoter induced by LPS can improve symptoms such as acne through anti-inflammatory action.

In this Test Example 2, the NF-κB inhibition test was carried out as follows using the principle described above. First, using a NF-κB promoter Gaussia luciferase vector in a 96-well plate using a transfection reagent (Superfect, Qiagen, Germany) into RAW264.7 cells, a mouse macrophage line. Transfection was performed. 24 hours after transfection, the complex mixture of Example 2 (AquMix) was treated with 50 μl and 100 μl of the 96-well plate, respectively, and pre-treated for 2 hours in a 37 ° C. incubator. After completion of the pretreatment culture, 100 μl of LPS at a concentration of 0.5 μg / ml was added thereto, followed by incubation for 18 hours in a 37 ° C. incubator. Cell cultures were collected and reacted with a Gaussian luciferase substrate (NEB, USA) and then luminescence was measured using a Luminescence microplate reader (Infinite 200 Pro, Tecan, Swiss). The test results are shown in FIG. 2.

As can be seen in Figure 2, the complex mixture (Aqumix) according to the present invention inhibited the activity of the NF-kB promoter, through which it was confirmed that inhibits the production of inflammatory cytokines IL-8, TNF-α .

Test Example 3 Cytotoxicity Measurement of Complex Mixture (AquMix)

The stability of the complex mixture (Aqumix) on the human body was investigated. Specifically, cytotoxicity test (MTT) was performed using HaCaT cells, which are human keratinocyte lines. Each single extract and complex mixture of Example 1 were treated to HaCaT cells by concentration, and cultured for 1 day, and then the cytotoxic effect of the cells was determined by MTT (3- (4,5-dimetylthiazol-2-). yl) 2,5-diphenyltetrazolium bromide) analysis method. The test results are shown in Table 4 below.

Treatment concentration 0.001% 0.005% 0.01% 0.025% 0.05% Cell survival rate
（Cell survival rate compared to negative control group） 103% 102% 98% 95% 92%

As a result, it was confirmed that there was no significant cytotoxicity up to 500 ppm of the AquMix treatment.

<Example 3> Preparation of external preparation for skin containing complex mixture (AquMix)

In order to confirm that the complex mixture (AquMix) according to the present invention is safe for human skin, a skin external preparation containing the complex mixture (AquMix) was prepared using the ingredients and contents shown in Table 1 below, and then a skin stability and clinical efficacy assay was performed. It was. First, purified water, glycerin and butylene glycol were mixed and dissolved at 70 ° C. (water part), and the other components except the three components and trimethanolamine were dissolved at 70 ° C. (oil part). The oil part was added to the water part and stirred with a homomixer (Tokushu Kika, Japan) to emulsify first. After the final addition of trimethanolamine, bubbles produced in the mixed solution were removed and cooled to room temperature to prepare an external preparation for skin.

ingredient content (%) Control Test group 1 Purified water 72 72 glycerin 8.0 8.0 Butylene glycol 4.0 4.0 Complex Mixture of Example 2 (AquMix) 0 2.0 Caprylic Capri Triglyceride 8.0 8.0 Squalane 5.0 5.0 Cetearyl Glucoside 1.5 1.5 Sorbitan stearate 0.4 0.4 Cetearyl Alcohol 1.0 1.0 Trimethanolamine 0.1 0.1 Gross weight 100 100

<Test Example 3> Measurement of the oil content reduction effect of the composite mixture (AquMix)

3-1. Human clinical application of external preparations containing complex mixtures (AquMix)

The human clinical application test was conducted for 20 weeks on 20 men and women (12 females and 8 males) with facial acne severity grades 1 to 3 or older using a skin external preparation prepared in Example 3. After cleansing in the morning and evening, take an appropriate amount to spread evenly on the face and use twice a day, and before the product, after 2 weeks, 4 weeks after use, the oil content, sebum measurement and visual evaluation by a specialist.

For mechanical evaluation, the test subject was allowed to settle for 30 minutes in a waiting room with a constant temperature and humidity of room temperature 20 ~ 25 ℃ and humidity 40 ~ 60% to adapt the skin surface temperature and humidity to the environment of the measurement space. While the water intake was limited. One investigator was measured for objective measurement, and the same site was measured at each measurement.

3.2. Determination of the oil content reduction effect of the complex mixture (AquMix)

In order to confirm the oil content change by the use of the external preparation for skin prepared in Example 3, ug / ml values were measured before use, after 2 weeks, and after 4 weeks of use. The oil content was measured by using a Sebumeter SM815 (Courage-Khazaka eletronic GmbH, Germany) to determine the glacial area of the T zone. The measurement was performed once every 20 seconds and used as the data for skin oil content evaluation. Severmeter is a device that measures oil content per unit area (μg / cm ² ) by photometric reflection and measures sebum amount obtained for about 20 seconds after contacting special semi-transparent lipid absorbing tape to skin. Values and oil fractions are proportional.

The measurement results are shown in Table 6 below, and FIGS. 3 and 4. Figure 3 is a graph showing the oil content over time when using the external preparation for skin containing the complex mixture (AquMix) of the present invention, Figure 4 is the rate of change of oil content over time when using the external preparation for skin containing the complex extract of the present invention The graph shown.

(Mean ± SD) division ㎍ / ㎠ Skin external preparation of Example 3

Before use 134.20 ± 87.50 2 weeks after use 99.40 ± 43.64 4 weeks after use 69.50 ± 36.08 Military comparison
Before use-2 weeks after use 0.075 Before use-4 weeks after use 0.009 *

*: p <0.05 by repeated ANOVA, post hoc Bonferroni correction

As a result, the measured oil content was 134.20 ± 87.50 before use, 99.40 ± 43.64 after 2 weeks, and 69.50 ± 36.08 after 4 weeks. As a result of the post test according to the normality test, the measured oil content decreased significantly (p <0.05) after 4 weeks of use compared to before use.

<Test Example 4> sebum reduction effect of the composite mixture (AquMix) measurement

In order to confirm the sebum change by the use of the test product by using the external preparation for skin prepared in Example 3, the ea value was measured before use, 2 weeks after use, and 4 weeks after use. Sebum measurements were taken of the entire face using a Janus device. The T zone area was designated and analyzed in the image of facial images and used as sebum evaluation data. In the analyzed image, sebum is represented by red dots (oxidized sebum), which means that sebum improves as the number of red dots decreases.

Test results are shown in Table 7 and FIGS. 5 and 6. 5 is a graph showing the sebum measurement value over time when using the external preparation for skin containing the complex mixture (AquMix) of the present invention, Figure 6 is a time-dependent use of the external preparation for skin containing the complex mixture (AquMix) of the present invention It is a graph showing sebum change rate.

(Mean ± SD) division ea Skin external preparation of Example 3

Before use 124.80 ± 132.21 2 weeks after use 102.14 ± 108.34 4 weeks after use 115.80 ± 128.85 Military comparison
Before use-2 weeks after use 0.252 Before use-4 weeks after use 0.031 *

#: p <0.025 (= 5% / 2) by Fridman test, post hoc Wilcoxon singned rank test with Bonferroni correction

As a result, the sebum measurement value was 124.80 ± 132.21 before use, 102.14 ± 108.34 after 2 weeks of use, and 115.80 ± 128.85 after 4 weeks of use. According to the normality test, the test by the non-parametric Friedman test and post-test by Wilcoxon signed rank test and Bonferroni correction resulted in a significant decrease in sebum measurements after 4 weeks of use (p <0.025 (= 5% 2). ))

<Test Example 4> Effectiveness and product symbol of the composite mixture (AquMix)

Very good (4), good (3), moderate (2), bad (1), very bad (0) as shown in Table 8 for the acne skin compatibility according to the external preparation of the skin prepared in Example 3 The efficacy of the test product was investigated by answering the questionnaire directly in 5 steps. The investigator determined the efficacy of the test product by obtaining the percentage of the subjects for each answer.

Number of subjects (percentage,%) Average Standard
Deviation * 5 *4 * 3 *2 *One Suitable for acne skin use 2
(10.0) 8
(40.0) 8
(40.0) One
(5.0) One
(5.0) 3.45 0.94 * 5: Very good, 4: Good, 3: Normal, 2: Bad, 1: Very bad

As a result of the questionnaire evaluation of the effectiveness of the test product, 90% of the subjects evaluated 'acceptance' for the suitability of acne skin use.

<Test Example 5> Safety evaluation of the external preparation for skin containing a complex mixture (AquMix)

For the safety of the test product, the incidence rate of the adverse reaction was calculated by combining the identified adverse reactions among all test subjects using the test product and all the reported adverse reactions during the test period, and used as the safety evaluation data of the product. If the subject feels abnormal during the use of the test product, the investigator is required to report it immediately. When adverse reactions were reported, the extent of symptoms and association with the test product were determined, and appropriate measures for the symptoms and participation in the test were determined.

There were no reports of specific skin adverse events during the study period, and no abnormal findings were observed by the dermatologist.

<Example 1>: Cosmetic preparation

1-1. Flexible Cosmetics

ingredient weight% Complex Mixture of Example 2 (AquMix) 0.01 glycerin 3.0 Butylene Glycol 2.0 Propylene glycol 2.0 Carboxy Vinyl Polymer 0.1 ethanol 10.0 Triethanolamine 0.1 Preservatives, Micro Pigments, Micro-Fragrances and Micro-Purified Water 82.79 sum 100.0

After mixing the above components, it was prepared in accordance with the conventional method for producing a flexible longevity.

1-2. Nutrition

ingredient weight% Complex Mixture of Example 2 (AquMix) 0.01 Beeswax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 Liquid paraffin 5.0 Squalane 5.0 Caprylic / Capric Triglycerides 5.0 glycerin 3.0 Butylene Glycol 3.0 Propylene glycol 3.0 Carboxy Vinyl Polymer 0.1 Triethanolamine 0.2 Preservatives, Micro Pigments, Micro-Fragrances and Micro-Purified Water 69.69 sum 100.0

After mixing the above components, it was prepared in accordance with the production method of ordinary nutrient cosmetics.

1-3. Nutrition Cream

ingredient weight% Complex Mixture of Example 2 (AquMix) 0.01 Beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 Liquid paraffin 10.0 Squalane 5.0 Caprylic / Capric Triglycerides 5.0 glycerin 5.0 Butylene Glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, Micro Pigments, Micro-Fragrances and Micro-Purified Water 56.79 sum 100.0

After mixing the above components, it was prepared in accordance with the usual manufacturing method of nutrition cream.

1-4. Massage cream

ingredient weight% Complex Mixture of Example 2 (AquMix) 0.01 Beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Caprylic / Capric Triglycerides 4.0 glycerin 5.0 Butylene Glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, Micro Pigments, Micro-Fragrances and Micro-Purified Water 27.49 sum 100.0

After mixing the above components, it was prepared in accordance with the conventional method for producing a cream.

1-5. pack

ingredient weight% Complex Mixture of Example 2 (AquMix) 0.01 Polyvinyl alcohol 13.0 Sodium Carboxymethylcellulose 0.2 Allantoin 0.1 ethanol 5.0 Nonylphenyl Ether 0.3 Preservatives, Micro Pigments, Micro-Fragrances and Micro-Purified Water 81.39 sum 100.0

After mixing said components, it manufactured according to the manufacturing method of a normal pack.

Formulation Example 2: Pharmaceutical Formulation

2-1. Ointment

ingredient Content (g) Complex Mixture of Example 2 (AquMix) 10.0 Olive oil 14.5 beeswax 3.7 1,3-butylene glycol 6.3 Paraoxybenzoic acid propyl 0.1 Methyl paraoxybenzoate 0.2 Hydrolyzed fibroin 2.0 water 15

The above ingredients were mixed and stirred with a stirrer to prepare an ointment.

2-2. cream

ingredient Content (g) Complex Mixture of Example 2 (AquMix) 5 Stearic acid 1.5 Stearyl alcohol 2.2 Butyl Stearate 0.5 Propylene glycol 0.5 Glycerin Monostearate 2.0 Potassium hydroxide 0.3 Cream base 40

After mixing the above components, degassing, filtration and cooling to prepare a cream.

As such, the complex extract of tangerine peel, onion, wolfberry, licorice, white willow leaves and spinach according to the present invention; Rice bran hydrolysate; And niacin amide; the composition comprising a complex mixture prepared by mixing as an active ingredient inhibits the growth of acne disease-related microorganisms, regulates the division and sebum secretion of sebocytes, and improves the keratinization of hair follicles It not only has exfoliation but also reduces the oil content and sebum secretion of acne skin. In addition, the composition comprising a complex mixture (AquMix) according to the present invention can be used safely in long-term use because there is little toxicity and side effects, and in particular can be safely applied to cosmetic or external skin composition. In particular, since it is water-soluble, it can be applied to the development of transparent properties such as transparent skins without a solubilizer that can stimulate.

Claims (4)

Complex extracts of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; And niacin amide; Antimicrobial, anti-inflammatory, exfoliation and sebum reduction cosmetic composition comprising a complex mixture of mixed as an active ingredient. The method of claim 1,
The complex mixture is based on 100 parts by weight of tangerine peel extract, onion extract 800 to 1,000 parts by weight, wolfberry extract 800 to 1,000 parts by weight, licorice extract 100 to 200 parts by weight, white willow leaf extract 100 to 200 parts by weight and spinach extract 20 to 40 parts by weight, 100 to 200 parts by weight of rice bran hydrolyzate, and 800 to 1,000 parts by weight of niacinamide, characterized in that the cosmetic composition for antibacterial, anti-inflammatory, exfoliation and sebum reduction. Complex extracts of tangerine peel, onion, wolfberry, licorice, white willow leaf and spinach; Rice bran hydrolysate; And niacin amide; Antimicrobial and anti-inflammatory pharmaceutical composition comprising a complex mixture of the mixture as an active ingredient. The method of claim 3, wherein
The complex mixture is based on 100 parts by weight of tangerine peel extract, onion extract 800 to 1,000 parts by weight, wolfberry extract 800 to 1,000 parts by weight, licorice extract 100 to 200 parts by weight, white willow leaf extract 100 to 200 parts by weight and spinach extract 20 to 40 parts by weight, 100 to 200 parts by weight of rice bran hydrolyzate, and 800 to 1,000 parts by weight of niacinamide, the pharmaceutical composition for antibacterial and anti-inflammatory.

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