KR101219520B1 - Anti-inflammatory, anti-oxidative or anti-bacterial compositions - Google Patents

Abstract

The present invention relates to an anti-inflammatory, antioxidant or antibacterial composition containing carotenoids, phytosterols, polyphenols, mixtures of propolis and cordycepin as active ingredients, and rare earth elements.

Carotenoids, phytosterols, polyphenols, propolis, cordycepin, cerium, praseodymium, promethium, europium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, scandium, yttrium, lanthanum, neodymium, samarium, gadolinium, lutetium, anti-inflammatory, Antioxidant, antibacterial

Description

Anti-inflammatory, anti-oxidative or anti-bacterial compositions

The present invention relates to an anti-inflammatory, antioxidant or antibacterial composition, and more particularly, to an anti-inflammatory, antioxidant or anti-inflammatory agent containing a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepin, and rare earth elements as active ingredients. It relates to a bacterial composition.

Carotenoids are pigments found in many fruits and vegetables that provide yellow, orange, and red color and act primarily as antioxidants. In particular, lycopene in tomatoes is known to inhibit the development of colorectal and bladder cancer. Carotenoids in carrots and spinach may reduce the incidence of lung cancer.

Phytosterols are phytochemicals obtained naturally from plants and are steroidal alcohols. It is soft and white in color and has a characteristic odor, and beta-sitosterol, ergosterol, stigmasterol, stigmasterol, campesterol, and polycosanol are known. Ergosterol is found in many yeasts and mushrooms, and vitamin D ₂ is produced by irradiation with ultraviolet rays as a precursor of vitamin D. Sitosterol is present in many seeds, and stigmasterol is contained in soybeans. Policosanol is a mixture of eight high aliphatic primary alcohols purified from sugarcane wax, the most of which is octacosanol, tetracosanol, hexacosanol, heptaxosanol, It contains nonacosanol, triacontanol, dotriacontanol and tetratricontanol, and keeps blood vessels healthy through HDL and LDL levels. Phytosterols are known to lower cholesterol levels in vivo. Their in vivo mechanisms have not yet been established, but they reduce the absorption of dietary or endogenous cholesterol in the intestine. Phytosterols are widely used as medicines, cosmetics, food additives, and dietary supplements. In addition, it is effective in anti-inflammatory and skin immunity, and has a wrapping effect that wraps the skin moist, helping to maintain healthy skin.

Polyphenols have been reported to lower the risk of various diseases due to their high antioxidant capacity to protect DNA damaged by exposure to free radicals in vivo or to protect cellular proteins and enzymes. In addition, recent epidemiologic studies have shown that polyphenols have a protective effect on heart disease, suggesting that red wine and flavones and flavonol intakes can reduce heart disease mortality. Tea extracts have also been shown to reduce heart disease and cancer. Polyphenols include flavonoids such as catechins and isoflavones, stilbenes such as resveratrol, and lignans. Flavonoids, which are herbal ingredients of plants, are contained in a large amount of leaves, flowers, fruit stems, fruits, vegetables, green tea, etc., and have antioxidant, antibacterial, antiviral, antiallergic, and anti-inflammatory effects. In addition, the flavonoid-based black pigment isoflavone (isoflavone) regulates the secretion of female and male hormones.

Propolis, a natural antibiotic called nature's penicillin, contains white blood cells to fight off bacteria that enter the body. Trees protect the growth points, prevent contamination of wounds, and block microorganisms. It is a substance secreted by itself. Propolis is used as a raw material for antibacterial, antiviral, antiseptic, antifungal, and antibiotics. Since it is not harmful to the human body, it has no side effects or resistance and is effective for treating wounds and ulcers inside and outside the body. It also prevents and improves the skin. Numerous studies and treatments have demonstrated the effectiveness of propolis to enhance immune tissues. In particular, flavonoids, a type of antioxidant contained in propolis, are known as a major component directly related to the body's immune system.

Cordycepin is a natural substance contained in mushrooms and is known as a natural antibiotic and immune enhancing substance. The study of a substance called cordycepin began in 1951 with Professor Cunningham, and numerous scientific papers have been published internationally.

Rare earth elements include cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), and ytterbium ( Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), and lutetium (Lu) are trace metals containing about 0.016% in the earth's crust 15 elements (La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu) and 2 groups 3A in the periodic table of the elements In total, it refers to minerals containing 17 elements in total. These are elements that are almost similar in physical and chemical properties to each other and are separated from each other, but it is possible to separate them into single elements with slightly different differences. Each element is present in the form of a salt ion-bonded with a counterion, for example in the form of sulfates, nitrates, carbonates, acetates, phosphates, chlorides, or oxides, including hydroxides. Can be. The element has been discovered for over 200 years and is not well known to the general public, but its useful value is very large because it exhibits unique physical and chemical performances due to the unique electronic structure of each element. Like fluorescent materials, they are used in machinery, petrochemical, photochemistry, etc., and recently, applications have been attempted in various fields such as agriculture, forestry, and livestock industry. Furthermore, as a biological effect, each element promotes photosynthesis and chlorophyll formation in higher plants, promotes germination of shoots, vitalizes roots, activates respiratory activity, promotes nutrient movement in the body, regulates moisture, promotes cell division, promotes transfer of hormones, and nutrients. It promotes absorption and body movement, activates metabolism, increases RNA and protein synthesis in leaves, delays the aging process of leaves, increases protein content of green algae, promotes photosynthesis and oxygen release activity, and promotes protein and chlorophyll. Promotes formation. Among them, La ³⁺ is known to enhance the function of Ca ²⁺ ions in the body by increasing the activity of (Na ⁺ , K ⁺ ) -ATP enzyme and Mg ²⁺ -ATP enzyme of human erythrocyte cell membranes (The Journal of Biological Chemistry; 1986; 261 (20); 9552-9557], some elements have antibacterial effects (Chem. Pharm. Bull .; 2003; 51 (5); 494-498), free radicals Inhibits production, exhibits antioxidant activity (Biochemical and Biophysical Research Communication; 2006. 2; 342; 86-91), and promotes weight gain and feed conversion in growing hog pigs (J. Anim. Physiol.a.Anim.Nutr .; 2001; 85; 263-270] .Also, each element belongs to a low-toxic substance, with very little absorption through the digestive system, no specific body accumulation, Have not been shown to cause or mutate or cause cancer (Environmental Health Perspectives). ; 1996; 104; 85-95].

Inflammation is one of the defenses of biological tissues against certain stimuli. It is a complex lesion that involves three kinds of tissue degeneration, circulatory disorder and exudation, and tissue proliferation. In addition to having a terminal salt, such as otitis media, the general term for lesions seen in infectious diseases (tuberculosis, syphilis, dysentery, diphtheria, etc.), and most diseases belong to this. The cause is due to mechanical injury, physical factors such as temperature, radiation, chemical factors such as poisons, parasites such as bacterial infection, etc., and most of them are caused by bacteria. In addition to these main causes, the occurrence is complicated by various concomitant factors and predisposition or immunity of the individual. The course is divided into acute, subacute, or chronic. Inflammation is classified into ① degenerative inflammation ② exudative inflammation: serous inflammation, fibrinous inflammation, purulent inflammation, hemorrhagic inflammation, decaying inflammation, catarrhal inflammation ③ proliferative inflammation ④ specific inflammation: tuberculosis, syphilis, leprosy, actinomycosis (I) and beads;

EGF (Epidermal Growth Factor), which is a factor involved in inflammation, is produced in platelets as an epidermal growth factor and is found in the early stages of wound healing. It is found in the kidneys, salivary glands, and lacrimal glands, so it is found in high concentrations in urine, saliva, and tears. Its angiogenic function promotes vascular endothelial cell division and helps blood vessels regenerate, and stimulates fibroblasts in dermal tissue to collagen. Promotes secretion to fill granulation tissue and promotes epithelial cell division and migration to cause re-epithelialization. Platelet Derived Growth Factor (PDGF) is produced in platelets (most secreted), macrophages, vascular endothelial cells and fibroblasts, and is very important for strong chemoattractants, fibroblasts, and extracellular matrix for fibroblasts and vascular smooth muscle. It promotes the production of fibronectin and hyaluronic acid and is involved in the production of collagenase, which is important for wound healing. Epithelial and endothelial cells do not have PDGF receptors and indirectly promote the formation of new blood vessels. Among other growth factors, the transforming growth factor-β (TGF-b) superfamily is composed of many similar proteins in structure. These are dimers, acting as hormones or mediators. TGF-β is a homolog of molecular weight 25 kDa that regulates early development, cell cycle regulation, cell proliferation and differentiation, migration, survival, production of extracellular matrix, immune system, and blood vessel formation in various cell and tissue types. It is known as a multifunctional cytokine that regulates blood cell production, cell death induction, skeletal formation, and wound healing. TGF-β has three isomers of TGF-β1, TGF-β2 and TGF-β3, which are the receptors of TGF-β receptor type I (TGFβR-I) and TGF-β receptor type II (TGFβR-II) Signal is transmitted through heterologous complex receptors. Vascular epidermal growth factor (VEGF) is a homologous glycoprotein and is the most common and effective growth factor known to stimulate angiogenesis at the wound site. Therefore, VEGF is expressed in many vascular tissues, and is known as a mitogen specific to epithelial cells, inducing the migration and proliferation of epithelial cells and increasing the permeability of blood vessels. Their effect is regulated through epithelial cell receptors Flt-1 and Flk-1 / KDR having protein-tyrosine kinase domains.

Normal production, which is part of everyday life, including energy production through breathing in the living body, prevention of disease through immune activity, detoxification in the liver when toxic substances are administered in vivo, activities to balance the living body, and exercise Despite being an activity of life, ROS (Reactive Oxygen Species) are produced from these activities. In a healthy state, the rate of ROS formation does not reach the rate of ROS removal in the antioxidant system of biological tissues. Therefore, it is essential for all organisms that use oxygen to maintain a balance between prooxidants and antioxidants, and if the balance is broken, the oxidants may prevail and cause oxidative damage. It is defined as 'oxidative stress'.

As much as 21% oxygen exists in the atmosphere, all living things, including humans, use this oxygen to carry out life activities. However, oxygen, which is essential for living organisms, also becomes a singlet oxygen ( ¹ O ₂ ) or hydrogen peroxide from normal ground triplet oxygen ( ³ O ₂ ), which causes damage to DNA in the living body and causes cellular dysfunction such as carcinogenesis and mutations. It is known to be involved in aging, arteriosclerosis, fatigue and adult diseases. As such, all living aerobic breathers produce radicals and free radicals during normal metabolism. That is, free radicals naturally occur due to respiration in mitochondria, the action of monocytes, and reactions of various enzymes. Because these free radicals have a high chemical affinity, they react with all cellular components to change the structural and functional properties of cells. Bring it. Proper amounts of free radicals have a positive effect on the phagocytosis of macrophages and macrophages in the body related to immune function in vivo. However, excessive amounts of free radicals can lead to protein denaturation, biofilm lipid peroxidation, and DNA degeneration. Causing oxidative stress. That is, the -SH group of the protein reacts with the active oxygen to lose the activity of the enzyme and causes cell death by membrane damage due to oxidation of the biological membrane.

Lipid peroxidation is initiated by the binding of free radicals to unsaturated fatty acids that make up phospholipids, which are the major components of cell membranes. Due to the lipid peroxidation reaction, the phospholipids constituting the cell membrane are broken down into alcohol, ketones, and aldehydes, thereby losing the normal function of the cell membrane. These degradation products inhibit the activity of enzymes and are known to cause cell necrosis and microvascular lesions.

Free radicals generated in vivo or externally can cause fatal damage to tissues such as lipid peroxidation, protein destruction, chromosomal abnormalities and erythrocyte destruction, but tissues contain endogenous scavengers to protect against free radical damage. do. In vivo antioxidant defense systems are primarily maintained by the wide distribution and organic association of antioxidant enzymes. Superoxide dismutase (SOD), a key component of the antioxidant defense system, is divided into FeSOD (prokaryotes and chloroplast substrates), MnSOD (protozoa and eukaryotes mitochondria), and Cu / ZnSOD (cytoplasm and chloroplast enzymes). usually, was converted to the O ^2- H ₂ O _2, catalase (catalase) serves to remove intracellular radicals by decomposing the H ₂ O ₂ with water. Glutathione peroxidase (GPx) converts H ₂ O ₂ to water and simultaneously converts reduced glutathione (GSH) to oxidized glutathione (GSSG), and the resulting GSSG is a glutathione reductase GR) back to GSH. At this time, NADPH acts as an electron transporter, providing reducing power to GSSG. NADPH is made in NADP ⁺ by glucose-6-phosphate dehydrogenase (G6PDH) and isocitrate dehydrogenase (ICDH).

The present inventors have conducted continuous research to develop excellent anti-inflammatory, antioxidant or antibacterial compositions without causing side effects that are safe for the human body. The result is a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepin, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), and lutetium New and surprising facts have been found to complete the present invention that the combination of one or more rare earth elements selected from (Lu) can result in significantly superior effects by unexpected synergies between the two components.

Therefore, an object of the present invention is an active ingredient, a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepin, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb) Dysprosium (Dy), Holmium (Ho), Erbium (Er), Thulium (Tm), Ytterbium (Yb), Scandium (Sc), Yttrium (Y), Lanthanum (La), Neodymium (Nd), Samarium (Sm) To provide an anti-inflammatory, antioxidant or antibacterial composition containing at least one rare earth element selected from gadolinium (Gd) and lutetium (Lu).

The present invention is an active ingredient,

Iii) a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepin; And

Ii) Cerium (Ce), Praseodymium (Pr), Promethium (Pm), Europium (Eu), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Erbium (Er), Thulium (Tm), Ytterbium (Yb) ), One or more rare earth elements selected from scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu), or salts or oxides thereof:

It relates to an anti-inflammatory, antioxidant or antibacterial composition containing.

The composition according to the present invention not only shows a remarkably good anti-inflammatory, antioxidant or antibacterial effect by the unexpected synergy between a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepine, and rare earth elements, and is harmless to humans. safe.

Hereinafter, the present invention will be described in detail.

We have a mixture of carotenoids, phytosterols, polyphenols, propolis and cordycepin, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), and lutetium It has been found for the first time that an unexpected synergy between two components in combination between one or more rare earth elements selected from (Lu), or salts or oxides thereof, results in significantly superior anti-inflammatory, antioxidant or antibacterial effects.

Carotenoids, phytosterols, polyphenols, propolis and cordycepin used in the present invention are not limited to a special kind as long as they play a role of enhancing the action effect of rare earth elements, but are not limited to beta-carotene (β) at least one of -carotene and lycopene; As phytosterols beta-sitosterol, ergosterol, stigmasterol, stigmasterol, campesterol, octacosanol, tetracosanol, hexacosanol, hexacosanol, heptacosanol One or more of heptaxosanol, nonacosanol, triacontanol, dotriacontanol and tetratricontanol; As polyphenols, one or more of catechin, epicatechin, quercetin, flavonoids, stilbene and lignans can be used. Preferably, lycopene is used as the carotenoid, hexacosanol is used as the phytosterol, and catechin is used as the polyphenol. In the present invention, carotenoids, phytosterols, polyphenols, propolis and cordycepin may be naturally-occurring or artificially synthesized.

Cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), used in the present invention Ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu) are obtained from nature such as soil, natural rock and seawater. It is preferable to use the ones, especially those contained in loess, clay, red soil or deep sea water. The element may be used by grinding into fine powder. The element may be used in the form of a single element or a mixture of two or more elements, and may be used in the form of a salt, for example, in the form of sulfate, nitrate, carbonate, acetate, phosphate, chloride or the like, or in the form of an oxide including a hydroxide.

In the present invention, the compounding ratio of each component is not particularly limited as long as the desired synergy can be exhibited. The weight ratio of carotenoid: phytosterol: polyphenol: propolis: cordycepin is preferably 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5, more preferably 1: 1: 1: 1: 1 : 1 The weight ratio of iii) and ii) may be from 1: 1 to 100: 1, preferably from 1: 1 to 50: 1, more preferably from 1: 1 to 10: 1 and most preferably from 10: 1. . The composition of the present invention preferably contains 0.0001 to 10% by weight, more preferably 0.01 to 1% by weight, most preferably 0.1 to 1% by weight. This is because the desired synergy can be maximized within the above range, but the scope of the present invention is not limited to the above specific range.

The composition according to the present invention can be used to prevent, treat or ameliorate diseases caused by inflammation or oxidative stress or bacteria, for example, atopic dermatitis, wounds or lacerations, acne, keratin, insect bites. It can be used for skin barrier recovery or moisturizing.

The composition of the present invention ginseng, ginseng, Tangerine dermis, green tea, carrot, bellflower, lettuce, Seomoktae, pomegranate, pine needles, moonflower, cypress leaf, sesuo, nasturtium, tribulus extract, betaine, peppermint extract, nettle extract, horsetail extract, lavender extract , Hop extract, aloe, bramble, cordyceps, bokbunja, mulberry, vinegar, astragalus, donkey, wolfberry, hawthorn, grape, safflower, sesame, perilla, persimmon, garlic, kelp, seaweed, plum, green bean, black rice, root skin, 칡, persimmon leaf tea , Rooibos tea, evening primrose oil, nym tree, salt (sun salt, bamboo salt), vinegar, charcoal, chrysanthemum, licorice, reinforcement, stalk, sea bream, ant black sesame, mistletoe, cinnamon, morel cabbage, mineral wood, bulbous, billet, gilkyung , Zelkova, elm, jujube, deodeok, poisonous tree, camellia, rhododendron, full bloom, malt, beetle, cedar, fig tree, dandelion, rock odor, half, windproof, baekbokyeong, baekryeok, baekjiryeo, baekheo , White flower, Bupyeong-cho, betel nut, mulberry, Sanchona , Triticale, ginger, saengjihwang, serpentine, changchang, seon, slushing root, purslane, swimming, horseback riding, shiho, new song, acacia flower, eoseongcho, omae, alligator, yeongseonseon, motherwort, indongcho, injin mugwort, red bokcho, jopi Tree, fruit room, stinger flower, oak bark, creation, shrine, celestial horse, gardenia, lacquer tree, earthenware, blood tree, Korean ginseng vine, pasqueflower, seaweed, juniper, hyangbuja, hyunghwa, namul, thick, black shaft, alfalfa, wheat, rice, Sugar cane, sorghum, corn, sunflower seeds, pentadecanoic acid, glycerides, hinokithiol, forskolin, tocopherol acetate, trans-3,4'-dimethyl-3-hydroxyflavanone (trans-3,4 tocopherols such as' -dimethyl-3-hydroxyflavanone), nicotinic acid, nicotinic acid amide, palmitic acid retinol, β-carotene, calciferol, folic acid, biotin, D-pantothenyl alcohol, acetylpantothenylethyl ether, calcium pantothenate, pantothenate Tenyl ethyl ether, ascorbic acid, grapefruit seed extract, three Rantin (cepharanthin), nicotinic acid benzyl ester, vitamin _{A, B 1, B 2,} B 6 ( pyridoxine) and the derivatives thereof, pantothenic acid and its derivatives, minoxidil, jajusseunpul extract, arginine, aspartic acid, methionine, serine, articles lysine, glutamic acid , Cystine, amino acid extract, β-glycyrrhetinic acid, glycyrrhizic acid, pyridoxine hydrochloride, salicylic acid, allantoin, photosensitive 301, isopropylmethylphenol, pyroctone olamine (Piroctone Olamine ), Glycerin, pyrrolidonecarboxylic acid, estradiol, ethynylestradiol and l-menthol. In addition, it may further include one or more from sugars such as monosaccharides such as glucose, xylose, mannose, arabinose and the like, disaccharides such as maltose, sucrose, cellobiose, trehalose, etc., which may serve to provide nutrition. The amount thereof is preferably 0.01 to 1% by weight of the total composition.

The compositions of the present invention may be formulated in unit dosage form further containing a pharmaceutically or cosmetically acceptable carrier or additive. The composition may be administered transdermally or orally, and for this purpose lotions, ointments, gels, creams, patches, sprays, tablets, pills, powders, sachets, elixirs ), Suspensions, emulsions, solutions, syrups, soft or hard capsules. The compositions of the present invention can be used as ointments, creams, lotions, sprays, soaps or cosmetics.

There is no particular limitation on the application of the composition, the composition of the present invention can be applied to humans, breeding or pets.

The dose of the active ingredient according to the present invention should be appropriately determined in consideration of sex, age, symptoms, disease state, and the like, and may be administered, for example, at a dose of 0.1 to 10 mg / kg per day.

Hereinafter, the present invention will be described in more detail with reference to specific examples, but the scope of the present invention is not limited by them in any way.

Example 1 Preparation of Atopic Treatment and Improvement Composition (milky lotion)

In this example, a composition was prepared using lycopene as a carotenoid, hexacosanol as phytosterol, and catechin as polyphenol.

(1) a mixture of lycopene, hexacosanol, catechin, propolis and cordycepin

Powdered lycopene, hexacosanol, catechin and cordycepin purchased from SIGMA (USA), and propolis capsules manufactured by Natures Care P / L (Australia) 1 The mixture was used in a weight ratio of 1: 1: 1: 1: 1.

(2) Preparation of Mixed Elements

Each element obtained in nature was micropowdered to 10 mu m or less using a mill. For the powdered element, purified water was mixed at a ratio of 1: 5, and then stirred at a constant speed of 60 to 120 rpm for 12 hours, and filtered using a 10 μm filter paper.

(3) Preparation of the composition

Using the ingredients and contents shown in Table 1, the mixed element powder, lycopene, hexacosanol, catechin, cordycepin and propolis (hereinafter referred to as 'LHCCP') were uniformly mixed and then filtered to prepare a composition.

ingredient Content (% by weight) One LHCCP 0.1 2 Mixed element 0.01 3 Wax 1.0 4 Vaseline 2.0 5 Squalene 5.0 6 lanolin 2.0 7 Cetyl alcohol 1.0 8 Propylene glycol 4.0 9 glycerin 4.0 9 POE (10) Monooleic Acid Ester 1.0 10 Glycerol Monostearic Acid Ester 1.0 11 Carboxylic Acid Vinyl Polymer 0.1 12 ethanol 5.0 13 antiseptic Proper amount 14 Antioxidant Proper amount 15 Spices Proper amount 16 Purified water Up to 100

(Mixed elements: Ce, Pr, Pm, Eu, Tb, Dy, Ho, Er, Tm, Yb, Sc, Y, La, Nd, Sm, Gd, Lu, mixture of same)

Example 2 Preparation of Composition (Latex) for Wound and Burn Treatment and Improvement

Except for using the components and contents shown in Table 1b, the compositions were prepared according to substantially the same procedures as described in Example 1.

ingredient Content (% by weight) One LHCCP 0.1 2 Mixed element 0.01 3 Cyclomethicone 5.0 4 Liquid paraffin 5.0 5 Propylene glycol 6.0 6 glycerin 4.0 7 Carboxyvinyl polymer 0.1 8 Dimethicone 5.0 9 Potassium hydroxide Proper amount 10 antiseptic Proper amount 11 Antioxidant Proper amount 12 Spices Proper amount 13 Purified water Up to 100

Example 3: Preparation of acne treatment and improvement composition (milk)

Except for using the components and contents shown in Table 1c, the compositions were prepared according to substantially the same procedure as described in Example 1.

ingredient Content (% by weight) One LHCCP 0.1 2 Mixed element 0.01 3 lanolin 2.0 4 Liquid paraffin 20.0 5 Squalene 10.0 6 Propylene glycol 7.0 7 Solbitan sesquioleic acid ester 4.0 8 POE (20) sorbitan monooleic acid ester 1.0 9 Wax 3.0 10 antiseptic Proper amount 11 Antioxidant Proper amount 12 Spices Proper amount 13 Purified water Up to 100

Example 4 Preparation of Composition (Cream) for Exfoliation Treatment

Except for using the ingredients and contents shown in Table 1d, the compositions were prepared according to substantially the same procedures as described in Example 1.

ingredient Content (% by weight) One LHCCP 0.1 2 Mixed element 0.01 3 Wax 10.0 4 Vaseline 15.0 5 Liquid paraffin 41.0 6 1,3-butylene glycol 4.0 7 Glycerin Monostearate 2.0 8 POE (20) sorbitan monolauryl ester 2.0 9 Solid paraffin 5.0 10 alkali borax 11 antiseptic Proper amount 12 Antioxidant Proper amount 13 Spices Proper amount 14 Purified water Up to 100

Example 5 Preparation of a Bite Bite Composition

Except for using the components and contents shown in Table 1e, the compositions were prepared according to substantially the same procedure as described in Example 1.

ingredient Content (% by weight) One LHCCP 0.1 2 Mixed element 0.01 3 lanolin 1.0 4 glycerin 1.0 5 Ethyl alcohol 50.0 6 Spices Proper amount 7 Purified water Up to 100

Comparative Examples 1 to 10 Preparation of Composition

In Examples 1 to 5, except that each component was mixed using only mixed elements without addition of LHCCP (Comparative Examples 1 to 5), or using only LHCCP without addition of mixed elements (Comparative Examples 6 to 10). The composition was prepared by substantially the same procedure.

Examples 6-90 Preparation of Composition

In Examples 1 to 5, except that the respective elements were used instead of the mixed elements as shown in Table 2, the compositions were prepared by substantially the same process.

basic
Example Example 1 Example 2 Example 3 Example 4 Example 5 Ce  Example 6  Example 23 Example 40 Example 57 Example 74 Pr  Example 7  Example 24 Example 41 Example 58 Example 75 Pm  Example 8  Example 25 Example 42 Example 59 Example 76 Eu  Example 9  Example 26 Example 43 Example 60 Example 77 Tb  Example 10  Example 27 Example 44 Example 61 Example 78 Dy  Example 11  Example 28 Example 45 Example 62 Example 79 Ho  Example 12  Example 29 Example 46 Example 63 Example 80 Er  Example 13  Example 30 Example 47 Example 64 Example 81 Tm  Example 14  Example 31 Example 48 Example 65 Example 82 Yb  Example 15  Example 32 Example 49 Example 66 Example 83 Sc  Example 16  Example 33 Example 50 Example 67 Example 84 Y  Example 17  Example 34 Example 51 Example 68 Example 85 La  Example 18  Example 35 Example 52 Example 69 Example 86 Nd  Example 19 Example 36 Example 53 Example 70 Example 87 Sm  Example 20 Example 37 Example 54 Example 71 Example 88 Gd  Example 21 Example 38 Example 55 Example 72 Example 89 Lu  Example 22 Example 39 Example 56 Example 73 Example 90

Experimental Example 1 Measurement of Cell Proliferation Promoting Effect

NIH 3T3 cells, mouse embryonic fibroblasts, were treated with 2 × 10 ⁶ or 4 × in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal calf serum (FBS) and 1% penicillin-streptomycin. Cultures were incubated in a 37 ° C. (95% O _2, 5% CO _2, 60% humidity) constant temperature and humidity incubator while maintaining a density of 10 ⁶ cells / ml. MTT assay method was used for the promotion of cell proliferation. For MTT experiments, 2 × 10 ³ cells / ml of each cell were dispensed into 96 well plates and treated with a culture solution containing 10% FBS. After stabilizing the cells for 24 hours in the incubator, the culture medium containing FBS was transferred to DMEM without FBS and mixed with 10 ㎍, 1 ㎍, 100 ng, 10 ng, 1 ng, 100 pg, 10 pg and 1 pg, respectively. And LHCCP and treated with 10 ng of mixed elements and 1 μg of each component (lycopene, hexacosanol, catechin, propolis and cordycepin). After incubation for a certain time, 50 μl of MTT (2 mg / 1 sterile distilled water) was added per well for 4 hours, followed by shaking for 30 minutes by treatment with dimethyl sulfoxide (DMSO), followed by eliza reader (550, The absorbance was measured at 540 nm using Bio-rad).

The results of treating the mixed elements or the LHCCP are shown in FIG. 1A, and the results of treating the respective components or mixing the components with the mixed elements are shown in FIG. 1B, respectively. As shown in Figure 1a, the experimental group treated with a mixed element from 10 ㎍ to 1 pg was confirmed that the proliferation of cells more active than the untreated group not treated with the mixed element. In particular, after the addition of the mixed elements it was confirmed that the increase to 136% compared to the untreated group, even when treated with LHCCP it was confirmed that increased to 127% than the untreated group. In particular, as shown in Figure 1b, when the mixed element (10 ng) and LHCCP (1 ㎍) mixed treatment was confirmed that the proliferation rate is significantly increased up to 160%. Therefore, it can be seen that the mixing of the mixed element and LHCCP affects the cell proliferation better than when the mixed element and LHCCP were treated respectively.

In addition, even when the individual components of the mixed elements were mixed with LHCCP, the cell proliferation increased by 30% or more on average compared to the untreated group, and also beta-carotene, beta, which are components of carotenoids, phytosterols, and polyphenols. -Sitosterol, ergosterol, stigmasterol, camphorsterol, octacosanol, tetracosanol, hexacosanol, heptacosanol, nonacosanol, triacontanol, dotriacontanol, tetratricontanol, epicatechin, quercetin In the case of flavonoids, stilbenes, and lignans, it was confirmed that the cell proliferation was increased when the mixed elements or their respective mixtures were treated compared to the untreated group. In particular, when treated with a mixed composition containing cerium (Ce) it was confirmed that the cell proliferation is the largest increase.

Experimental Example 2: Experiment of Removal of Free Radicals

To determine the free radical scavenging activity for antioxidant activity, the scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was measured.

After dissolving the sample in methanol (50 ppm), 160 μl was aliquoted into a 96 well microplate and mixed well with 40 μl of DPPH solution dissolved in methanol at a concentration of 1.5 × 10 ⁶ M. The reaction mixture was left at room temperature for 30 minutes and then measured by an ELISA reader at 520 nm. The result showed free radical scavenging activity compared to the control without addition of the sample, and L -ascorbic acid was used as the positive control.

The results are shown in Fig. As shown in Fig. 2, when the mixed element and LHCCP were treated alone. When the mixed element (10 ng) and LHCCP (1 ㎍) was mixed and treated, it showed a remarkably excellent free radical removal ability. In addition, even when the individual elements were mixed and treated, it was confirmed that the free radical removal ability was increased compared to the untreated group.

Experimental Example 3: Determination of anti-lethal concentration of cells due to hydrogen peroxide damage

Anti-lethal concentrations were measured in order to confirm the proliferation of cells by giving a constant damage to the cells. The lethal dose means when the cell proliferation rate is half that of the normal cell proliferation rate. The anti-lethal concentration of the cell growth recovery effect was measured under the same cell and culture conditions as in Experimental Example 1.

For MTT experiments, 2 × 10 ³ cells / ml of each cell were dispensed into 96 well plates and treated with a culture solution containing 10% FBS. After stabilizing the cells for 24 hours in the incubator, the culture medium containing FBS was transferred to DMEM without FBS and 1 mM, 900 μM, 800 μM, 700 μM, 600 μM, 500 μM, 400 μM, 300 μM, 200 μM, respectively. , Hydrogen peroxide was treated to a concentration of 100 μM. After 1 hour, 50 μl of MTT (2 mg / 1 sterile distilled water) was added per well, followed by reaction for 4 hours, shaken for 30 minutes by treatment with DMSO, and then 540 nm using ELISA reader (550, Bio-rad). The absorbance was measured at to determine the half-lethal concentration. The results are shown in Fig. As shown in FIG. 3, a semi-lethal concentration was obtained at 200 μM. The anti-lethal concentrations obtained in the experiments were used to investigate the effects of the composition after damaging the cells.

Experimental Example 4 Measurement of Cell Growth Recovery Effect by Hydrogen Peroxide Damage

Experiment of cell growth recovery effect was carried out under the same cells and culture conditions as in Experimental Example 1. The anti-lethal concentration of hydrogen peroxide 200 μM was treated to the cells to confirm the recovery ability by the mixed elements and LHCCP.

For MTT experiments, 2 × 10 ³ cells / ml of each cell were dispensed into 96 well plates and treated with a culture solution containing 10% FBS. After stabilizing the cells in the incubator for 24 hours, the culture medium containing FBS was changed to DMEM without FBS, and the first group (post-treatment group) treated 200 μM hydrogen peroxide for 1 hour to damage the cells and then mixed elements. (10 ng), LHCCP (1 μg), and mixed elements (10 ng) and LHCCP (1 μg) were mixed and treated, and the second group (pretreatment group) was mixed elements (10 ng) and LHCCP (1 μg). , And mixed elements (10 ng) and LHCCP (1 ㎍) mixed and treated for 24 hours and then 200 μM hydrogen peroxide for 1 hour to damage cells, the third group (simultaneous treatment group) 200 μM Hydrogen peroxide and mixed elements (10 ng), LHCCP (1 μg) and mixed elements (10 ng) and LHCCP (1 μg) were mixed and treated simultaneously. After 24 hours of incubation, 50 μl of MTT (2 mg / 1 ml sterile distilled water) was added per well for 4 hours, and then shaken for 30 minutes by treatment with DMSO, followed by 540 using ELISA reader (550, Bio-rad). Absorbance was measured at nm.

The results are shown in FIG. As shown in Figure 4, the treatment of each substance in all groups increased the cell proliferation capacity than when only hydrogen peroxide treatment. In particular, the mixed group (10 ng) and LHCCP (1 ㎍) mixed treatment showed better proliferation ability than the group treated with only the mixed element or only LHCCP in all three groups. On the other hand, even when treated with individual elements and LHCCP, it was confirmed that substantially the same effect as described above can be obtained.

Experimental Example 5: Determination of enzyme activity and measurement of lipid peroxidation by oxidative stress

In the same cell and culture conditions as in Experimental Example 1, 200 μM of hydrogen peroxide at a semi-lethal concentration was treated to the cells to measure enzymatic activity and lipid peroxidation by oxidative stress caused by mixed elements and LHCCP. 200 μM of hydrogen peroxide, the anti-lethal concentration, was treated with the cells and incubated for 1 hour, followed by incubation for 24 hours with the mixed elements (10 ng) and LHCCP (1 μg), respectively. The cultured cells were ultrasonically ground with ultrasonic grinding buffer (100 mM Tris, 10 mM MgCl ₂ , 10 mM NaCl, 10% glycerol, pH 7.5), and then a certain amount was taken without centrifugation, followed by determination of lipid peroxidation. To measure the activity of superoxide dismutase (SOD) and catalase (CAT), centrifuged at 15,000 rpm and 4 ° C. for 15 minutes. SOD activity was measured in 1 mM diethylenetri-aminepentaacetic acid with 0.1 mM EDTA and pyrogallol stock (10 mM HCl) in Tris-DE solution (50 mM Tris-HCl, pH 8.2). 20 mM blood were mixed galrol) was added to the protein extracted from the tissue measurement for one minute activity at 420 nm, and measuring the activity of the catalase is 0.01 M sodium phosphate buffer (pH 7.0) mixed with 0.015 MH ₂ O ₂ in the lungs The protein was extracted from the tissues and the absorbance was measured for 1 minute at 240 nm The lipid peroxidation was measured in 2 volumes of TBA-trichloroacetic acid (TCA) -HCl solution (0.375 in 0.25 N HCl) in 1 volume sample. % TBA / 15% TCA) was added to the water, which was then cooled and cooled for 15 minutes. Then, the mixture was centrifuged at 12,000 g for 10 minutes, and the supernatant was taken at 535 nm with a UV spectrophotometer (UV-2401PC, SHIMADZU). Absorbance was measured.

The results are shown in Fig. The left vertical axis shows the relative values of SOD and CAT, and the right vertical axis shows the relative values of lipid peroxidation. As shown in FIG. 5, the enzyme activity was increased in the mixed element treatment group, the LHCCP treatment group, the mixed element and the LHCCP treatment group, and the amount of lipid peroxidation was decreased compared to the untreated group. In particular, it can be seen that the composition treated with a mixed element (10 ng) and LHCCP (1 ㎍) affects the activity of antioxidant enzymes significantly superior to the group treated with only one substance. Lipid peroxidation by harmful radicals Protects the cell membrane from damage from action. From the above results, the composition according to the present invention is effective in mitigating or inhibiting damage to cells caused by harmful radicals caused by biological or metabolic processes, immune responses, or inflammatory reactions. It can be seen. Moreover, even when each individual element and LHCCP were mixed and processed, the effect similar to the above was confirmed.

Experimental Example 6 Determination of Enzyme Activity and Lipid Peroxidation in Experimental Animals

In order to measure the enzyme activity by oxidative stress and the amount of lipid peroxidation in experimental animals, acetone was periodically applied twice a day for 5 days on the back of hairless mice 8 to 10 weeks after birth. After the back skin was damaged, the compositions prepared in Example 1 and Comparative Example were applied continuously for 3 days twice a day at a dose of 400 μl per 10 cm ² of skin area. Thereafter, 1 g of each skin tissue of the back of the mouse treated with the composition according to Example 1 and the composition according to the comparative example was removed for 12 weeks, and foreign substances were removed with PBS (phosphate buffered saline) as much as possible, and then chopped with scissors. Cut and transfer to sonication buffer (50 mM Tris- / HCl, pH 7.5), 20 mM HEPES, 1 mM EDTA, 2 mM PMSF, 1% Triton-X 100. Then, the reaction was performed at 4 ° C. for 1 hour, and the tissue was separated by an ultrasonic mill to obtain proteins. Some of them were taken without a centrifugation, and the proteins were quantified and used for measuring lipid peroxidation. The rest was 15,000 rpm, After centrifugation at 4 ° C. for 15 minutes, the activity of SOD was measured. Thereafter, the enzyme activity and the amount of lipid peroxidation were measured in the same manner as in Experimental Example 5.

The results are shown in FIG. As shown in FIG. 6, the acetone treated group showed a threefold increase compared to the untreated group. This means that the phospholipids of the cell membrane result in more lipid peroxidation in the acetone treatment group. In the group treated with the composition of the example showed similar values to the untreated group, the group treated with the comparative composition did not show a significant difference from the acetone treated group. This indicates that by treating the composition according to Example 1, the cell membrane is protected from damage due to lipid peroxidation by harmful radicals. In the case of SOD, the untreated group and the example composition treated group showed similar tendencies, and the comparative composition treated group showed similar values to the acetone treated group. That is, it can be seen that the composition according to Example 1 removes harmful radicals and affects the activity of antioxidant enzymes. From these results, the composition according to the present invention mitigates or inhibits damage to cells caused by harmful radicals caused by immune or inflammatory reactions. Thus, the composition can be applied to atopic dermatitis or other skin diseases involving immune and inflammatory reactions. It can be seen that the treatment inhibits skin damage.

Experimental Example 7: Measurement of TGF, EGF, PDGF and VEGF Expression

In order to confirm the expression level of TGF, EGF, PDGF and VEGF by western blotting, the cells were cultured for 1 hour by treating 200 μM of hydrogen peroxide at a semi-lethal concentration with the same cells and culture conditions as in Experimental Example 1. Then, mixed elements (10 ng) and LHCCP (1 ㎍) were treated respectively and incubated for 24 hours. Proteins obtained from the cells were separated by 12% SDS-PAGE and transferred to a nitrocellulose membrane (NC). NC was then blocked with Tris buffered saline (TBS) containing 5% skim milk and diluted 1: 1,000 with primary antibodies (anti-TGF, anti-PDGF, anti-EGF and anti-VEGF rabbit IgG) and 1: After reacting with the secondary antibody (peroxidase-enveloped anti-rabbit IgG) diluted to 1,000, each was washed with TBS containing 0.05% Tween-20 and photosensitive to X-ray film using ECL detection kit. . The OD values were then graphed using an image analysis program from LabWork ™ (version 4.5.00.0).

The results are shown in Fig. As shown in Figure 7, it can be seen that the expression of all proteins is increased compared to the untreated group. This indicates that it is effective in repairing or treating pathological abnormalities of cells. Moreover, even when each individual element was mixed and processed, the above effects were confirmed.

Experimental Example 8: Measurement of TGF, EGF, PDGF and VEGF Expression in Experimental Animals

The experimental animals were 8 week-old ICR male rats (30 ± 3 g) and fed freely with general solid feed (Samyangsa) and water before the start of the experiment. (20 ~ 24 ℃, humidity 60 ~ 80%) preliminary breeding period was given. After the adaptation period, the hairs of the experimental animals were removed and wounds were made using a razor with a length of 1 cm, a width of 0.01 cm, and a depth of 0.5 cm, and lacerations were made using a round iron rod in an area of 1 cm in diameter. The experimental animal group was divided into the comparative example composition treatment group, the Example 2 composition treatment group, and the madecassol treatment group currently on sale. Each group maintained 24 hours a day, divided into 12 hours of light and cancer. The compositions prepared according to Example 2 and Comparative Example were applied to the wound site twice daily for a fixed amount (1 ml) in the morning and evening at regular times. All experiments were conducted to stabilize rats without testing when cancerous, and recovery period was allowed for 24 hours before the experiment.

In order to confirm the expression level of the protein by Western blotting, the animal was sacrificed and the tissues of the lesions were taken, cut into small pieces, and then homogenation buffer (50 mM). The tissues were disrupted with Tris- / HCl (pH 7.5), 1 mM EDTA (ethylenediaminetetraacetic acid), 2 mM PMSF (phenylmethane-sulfonyl fluoride), 1% Triton-X 100]. Proteins obtained from animal tissues were separated by 12% SDS-PAGE and transferred to nitrocellulose membrane (NC). NC was then blocked with Tris buffered saline (TBS) containing 5% skim milk and diluted 1: 1,000 with primary antibodies (anti-TGF, anti-PDGF, anti-EGF and anti-VEGF rabbit IgG) and 1: After reacting with the secondary antibody (peroxidase-enveloped anti-rabbit IgG) diluted to 1,000, each was washed with TBS containing 0.05% Tween-20 and photosensitive to X-ray film using ECL detection kit. .

The results are shown in FIG. As shown in FIG. 8, it can be seen that the expression of all proteins is increased in the case of the treatment composition of the example composition compared to the treatment composition of the comparative example. This indicates that it is effective in repairing or treating pathological abnormalities of the skin.

Experimental Example 9: grasp the anti-inflammatory effect

In order to determine the anti-inflammatory effect of the composition, NIH 3T3 cells, which are mouse embryonic fibroblasts, were used to investigate the inhibitory effect of protein kinase (PKC). The cells were incubated to 2 × 10 ⁷ cells / ml, and then reacted with a mixed element (10 ng) and LHCCP (1 μg). The cells were then washed with phosphate buffered saline (PBS) and then sonication buffer [50 mM Tris- / HCl (pH 7.5), 20 mM HEPES (N- [2-Hydroxyethyl] piperazin. -N '-[2-ethanesulfonic] acid, 1 mM EDTA (ethylenediamine-tetraacetic acid), 2 mM PMSF (phenylmethanesulfonyl fluoride), 1% Triton-X 100] were mixed with the ultrasonic crusher. In order to confirm the expression level of protein kinase by western blotting, the protein obtained from the cells was quantified, and a predetermined amount was separated by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by nitrocellulose. Transferred to nitrocellulose membrane (NC). NC was then blocked with Tris buffer solution (TBS) containing 5% skim milk, primary antibody (PKC) diluted 1: 1,000 and secondary antibody (peroxidase-enclosed anti-rabbit diluted 1: 1000). IgG), washed with TBS containing 0.05% Tween-20, and photosensitized the X-ray film using an ECL detection kit.

The results are shown in FIG. As shown in Figure 9, it can be seen that the activity of the PKC is suppressed by treating the mixed element and LHCCP. In view of the biochemical pathway of inflammation, PKC activity is increased by external stimulus, and then phospholipase D activity is increased, and the inflammatory reaction proceeds. The composition of the present invention inhibits the activity of PKC. It was confirmed that the inflammatory response can be suppressed. On the other hand, even in the case of treatment with individual elements, it was confirmed that substantially the same effects as described above can be obtained.

Experimental Example 10: grasp the anti-inflammatory effect of the composition

In order to determine the anti-inflammatory effects of the composition, the skin epidermal cells of NCNga mice, which are experimental animals, were used to examine the inhibitory effect of protein kinase C (PKC). The epidermal cells were cultured to 2 × 10 ⁷ cells / ml, and then reacted after adding the mixed elements and LHCCP. Then, the experiment was performed under the conditions of Experimental Example 7.

The results are shown in FIG. As shown in Figure 10, because the treatment of the mixed elements and LHCCP inhibited the activity of PKC it was confirmed that the following continuous inflammatory response can be suppressed. On the other hand, even in the case of treatment with individual elements, it was confirmed that substantially the same effects as described above can be obtained.

Experimental Example 11: Analysis of IgE Concentration in Cell Line

U266B1 cells (lymphoblastoma cell line), a human cell line producing IgE, were used to confirm the inhibitory effect of IgE production by mixed elements. U266B1 cells were grown at 37 ° C. in 24-well culture plates containing RPMI-1640 medium (15% FBS, 2 mM L-glutamine, 10 mM HEPES, 1 mM sodium pyruvate, 50 μg streptomycin, 100 U / ml penicillin added). Incubated in an environment of 5% CO ₂ . After adjusting the prepared cells to a concentration of 2 × 10 ⁵ cells / well, first, lipopolysaccharide (LPS) (2 μg / Ml) and treated with 1 μg of LHCCP, 10 ng of mixed elements, and 1 ng of LHCCP and 10 ng of mixed elements, and the control group was treated with dexamethasone (Dexamethasone, 2 μM) or medium (RPMI-1640). After culturing for 7 days under the same culture conditions, the IgE concentration of the medium was measured by ELISA reader (PharMingen; San Diego, CA).

The results are shown in Table 3.

LPS Stimulation process IgE (IU / mL) - RPMI-1640 187.1 ± 6.7 + RPMI-1640 401.1 ± 3.9 + LHCCP (1 μg) 387.4 ± 5.8 + Mixed element (10 ng) 312.9 ± 3.9 + Mixed element + LHCCP 217.1 ± 10.1 + Dexamethasone 207.9 ± 25.4

As shown in Table 3, the composition of the present invention showed an IgE production inhibitory effect similar to the control drug dexamethasone. On the other hand, even in the case of treatment with individual elements, it was confirmed that substantially the same effects as described above can be obtained. From these results, it was confirmed that by treating the composition containing the mixed element and LHCCP in atopic dermatitis or other skin diseases in which the immune response occurs, it showed that the suppression of the immune response than the treatment of each substance. In addition, when the individual elements and individual components were mixed and treated, the same effects as described above were confirmed.

Experimental Example 12 Analysis of IgE Concentration in Experimental Animals

Atopic dermatitis is a hypersensitivity reaction of the immune system that occurs when harmful substances such as allergens enter, and when harmful chemicals enter the body, B lymphocytes in the blood make immunoglobulin E (IgE), an antibody protein, and histamine. Release chemical transfer agents such as prostaglandins. Therefore, the concentration of IgE in serum was measured to confirm that the composition according to the present invention can reduce the production of antibody protein.

The composition obtained in Example 1 and the comparative example composition were each skin-coated (1 mg / day) on the neck of NCNga mice. Then, at 4 weeks, 8 weeks, and 12 weeks, a capillary tube was used to collect about 100 μl of blood from the eye of the mouse, and serum was isolated to measure the amount of IgE. The unit is μg / ml. The results are shown in Table 4.

As can be seen in Table 4, the composition treatment group according to Example 1 showed significantly lower IgE concentration than the composition treatment group according to the comparative example in the entire experimental process. Therefore, the composition according to the present invention was confirmed to be effective and persistent in reducing (treating) allergic reactions such as atopic dermatitis and insect bites.

Experimental Example 13: Measurement of tumor necrosis factor-α (TNF-α) production inhibitory effect of the composition according to the present invention

Whether the composition according to the present invention induces TNF-α production, an inflammatory cytoactive substance, was investigated as follows. In an IMDM culture medium containing 10% fetal bovine serum (FBS), mast cell lines HMC-1 were cultured at 5% CO ₂ , 37 ° C., and then divided into 3 × 10 ⁵ / mL cells. In order to stabilize the cells, the cells were pre-incubated at 37 ° C. for 10 minutes, and saline, mixed elements (10 ng / ml), and LHCCP (1 μg / ml) were added thereto, and then reacted for 24 hours. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g. ELISA experiments were performed to investigate the protein levels of TNF-α in the separated supernatants. Anti-human TNF-α (1 μg / ml), a monoclonal antibody to TNF-α, was diluted with PBS (pH 7.4), coated 100 μl each in a 96-well plate, and then left at room temperature for 12 hours. It was. The plates were washed with PBS containing 0.05% Tween-20 and then with PBS containing 1% bovine serum albumin (BSA), 5% sucrose and 0.05% sodium azide (NaN ₃ ). Blocked for time. After washing several times, the supernatant obtained by centrifugation and recombinant TNF-α to be used as a standard curve were added, and then left at 37 ° C. for 2 hours. Each well was then washed again and added to TNF-α (0.2 μg / ml) bound to secondary antibody biotin and left for another 2 hours at 37 ° C. The wells were washed and then avidin-linked peroxidase was added and left at 37 ° C. for 20 minutes. The wells were washed again, then ABTS [2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)] substrate was added and the color reaction was measured at 405 nm using an ELISA reader. The results are shown in Table 5.

TNF-α Secretion Untreated (saline) 0.264 ± 0.011 LHCCP (1 μg) 0.246 ± 0.024 Mixed element (10 ng) 0.229 ± 0.016 Mixed element + LHCCP 0.201 ± 0.019 Comparative example 0.256 ± 0.025

As shown in Table 5, it was confirmed that inflammatory skin diseases can be suppressed or treated by inhibiting TNF-α production, an inflammatory cell activator, by treating mixed elements and LHCCP in diseases involving atopic dermatitis or inflammatory reactions. . On the other hand, even when each individual element was mixed and processed, it was confirmed that the effect similar to the above can be acquired.

Experimental Example 14 Antimicrobial Test

Propionibacterium acnes , Staphylococcus aureus , Bacillus subtilis , Micrococcus spp., Aspergillus Aspergillus niger and Pityrosporum ovale , the causative agent of dandruff, were tested for antimicrobial activity. The medium used to test the antimicrobial activity against Propionibacterium acnes was 25 g of Brain Heart Infusion, 5 g of yeast extract, 4 g of casitatone, and 1 g of L-cysteine HCl in 1 L of distilled water. , 5 g of glucose, 1 g of soluble starch, 15 g of Monopotassium Phosphate, 1 g of ammonium sulfate, 0.2 g of magnesium sulfate, and 0.02 g of calcium chloride were dissolved in an equal amount and used after autoclaving. BBL GasPak anaerobic system was used. After the anaerobic condition was formed, the cells were incubated at 37 ° C. for about 3-5 days. After the incubation, the number of bacteria was measured to check the antimicrobial activity. Staphylococcus Medium 110 (Difco) was used for culturing Staphylococcus aureus, and Nutrient Agar was used for culturing Bacillus subtilis and Micrococcus, and Aspergillus niger Potato Dextrose Agar (Difco, Potato Dextrose Agar) was used for the culture, and 0.1% peptone, 0.5% glucose, 0.01% yeast extract, 0.4% oxbile, and 0.4% glyceryl mono were used for the cultivation of the Pytiros forum obale. A medium containing 0.05% stearate (glyceryl monostearate), 0.1% whole milk powder, and 0.1% glycerol was used.

The mixed element (10 ng) and LHCCP (1 μg) used in Example 3 of the present invention were dissolved in purified water. Each microorganism was cultured and diluted 10-fold sequentially, and then plated and cultured in each culture medium to determine the dilution factor that forms about 10 ³ to 10 ⁴ colonies per plate medium. Each microorganism was incubated and diluted with the dilution factor determined in the above experiment (0.85% NaCl was used as the dilution solution).

After diluting the sample prepared by the above method in the solvent used to prepare the sample, the desired concentration was added, and 1 ml of the diluted sample was added to 9 ml of the microorganism dilution solution and mixed well. For the control, the solvent used for sample dissolution was used. After standing at 37 ° C. for 30 minutes to 1 hour (sometimes mixed), 100 μl of the medium was smeared and then cultured in each culture condition, and the number of colonies was measured after the incubation.

11 is a table showing the antimicrobial activity of the present composition. The strains used in this antimicrobial test were Propionib bacterium acnes, Staphylococcus aureus, Bacillus subtilis, Micrococcus spp., Aspergillus niger and Pytilosforum obvale, the causative agent of dandruff. As shown in FIG. 11, it may be useful for the treatment of acne, dandruff, and eczema as well as secondary infections for atopy. On the other hand, even when each individual element was mixed and processed, it was confirmed that the effect similar to the above can be acquired.

Experimental Example 15: Measurement of Skin Barrier Recovery and Moisturizing Capacity of Experimental Animals

Tests were conducted to evaluate the effects of mixed elements (10 ng) and LHCCP (1 μg) on the recovery of the skin barrier due to prolonged skin damage. After acetone was applied twice a day for 5 days on the back of hairless mice 8-10 weeks after birth, impaired the back skin barrier function of the experimental animals, and prepared in Example 1 and Comparative Example. Transepidermal water loss (TEWL) was measured at regular intervals with an evaporator from Servaed, Sweden, for three days, with the composition applied twice a day for 3 days at a dose of 400 μl per 10 cm 2 skin area. 12 is shown.

Overall, the treated group containing the mixed element and LHCCP recovered the damaged barrier faster than the comparative treated group. As shown in FIG. 12A, as a result of measuring the relative amount of transdermal moisture loss, the amount of water loss in the Example treatment group was smaller than that of the Comparative Example treatment group. In addition, the amount of skin moisture measured using a coronometer (Corneometer, Courage Khazaka, Germany) at the time of TEWL measurement is shown in Figure 12b. As shown in FIG. 12, the skin moisture content of the treatment group containing the mixed element and the LHCCP was higher than that of the comparative treatment group, and the skin moisture content increased with the damage to the barrier. When the composition was used, the moisture retention was improved and the sustainability was excellent. Therefore, the loss of skin barrier caused by atopic dermatitis or other skin diseases can be reduced by the mixed element and LHCCP mixture to reduce the damage of the skin barrier. The Koniometer is a skin moisture meter that measures the amount of moisture present on the skin by measuring the conductivity of the epidermis.

Experimental Example 16: Clinical Experiment

In order to grasp the treatment and improvement effect of atopic dermatitis of the present invention, a clinical trial was conducted in atopic dermatitis patients. After checking the skin condition by measuring the water evaporation amount, water level, and pH of the lesion and non-lesion areas of the atopic dermatitis patient, the composition of Example 1 was applied twice a day for 2 weeks to determine the improvement of the skin condition. The treatment effect of atopic dermatitis was evaluated. In addition, the effect of the present invention was determined by comprehensively analyzing the palliative effect of the wound accompanied by itching, erythema and inflammation.

As shown in Table 6, in patients with atopic dermatitis, water loss (TEWL), water retention (hydration), and pH of the lesioned and non-lesioned regions show many differences. In the case of water loss, the loss of water in the lesion area was much higher than that of normal skin, and the water retention amount was less than 50 ~ 60 of normal, indicating that the skin is very dry. This indicates that the moisture barrier of the skin is severely damaged and the evaporation of moisture is severe. It can also be seen that the pH of the skin deviates somewhat around 5.5 of healthy skin. However, by applying the composition of Example 1 for two weeks, a lot of damaged skin was recovered, and a lot of moisture loss was reduced. In addition, the application of the composition of Example 1 to reduce the dryness of the skin, the itching is eliminated and do not scratch. In addition, itching was felt by the patient himself as shown in Table 7 it can be seen that significantly improved compared to before the application by applying the composition according to Example 1, it was confirmed that a lot of erythema, wounds healed.

-: No abnormality, +: not severe, +++++: very severe

Experimental Example 17 Measurement of the Histamine Release Inhibitory Effect of the Composition According to the Present Invention

In order to measure the histamine release inhibitory effect of the composition according to the present invention, the following experiment was performed.

The experimental animals were 12-week-old Sprague-Dawley male rats (average weight 350 g) of about 30 ml of Tyrode buffer B (137 mM NaCl, 5.3 mM glucose, 12 mM) in the abdominal cavity. NaHCO ₃ , 2.7 mM KCl, 0.3 mM NaH ₂ PO ₄ ) were injected and the abdomen was massaged for 90 seconds. Then, the peritoneum was carefully opened to collect Tyrod buffer B containing cells in the abdominal cavity with a Pasteur pipette. The cell-containing solution was then centrifuged at 150 x g for 10 minutes to precipitate the cells. Tirod buffer B was added to the precipitated cells, followed by pipetting, followed by slightly stacking on 22.5% metrizamide solution and centrifugation at 400 × g for 15 minutes to obtain only precipitated cells. Α-MEM (minimum essential medium) / 50% FBS (fetal bovine serum) was added to the precipitated cells and pipetted to mast cells by 95% or more by toluidine blue staining, and viability by trypan blue staining. It was confirmed that more than 90% was used in the experiment. Α-MEM / 50% FBS was added to the purified mast cells and carefully pipetted, and then divided into 2 × 10 ⁵ cells. In order to stabilize the cells, the cells were pre-cultured at 37 ° C. for 10 minutes, and treated with a mixed element and LHCCP for 30 minutes at 37 ° C. Shortly thereafter, Compound 48/80 (5.0 μg / ml each) was treated for 10 minutes. For reference, the compound 48/80 is a potent histamine release promoter is produced by condensation of methyl N- -p--methoxyphenyl ethyl amine (N-methyl- p -methoxyphenylethyl-amine ) and formaldehyde (formaldehyde), mast cells It is a substance mainly used to cause degranulation of mast cells by increasing intracellular calcium levels by increasing the inflow of calcium into the cells and decreasing intracellular cAMP levels by activating cAMP-phosphodiesterase. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g. Histamine quantification was measured at 440 nm by OPA phthaldialdehyde spectrofluorometry, and the inhibition rate of histamine secretion was calculated using the following equation.

Inhibition Rate (%) = [(A-B) × 100] / A

A: amount of histamine when no drug is added

B: amount of histamine when drug is added

The results are shown in Table 8.

Histamine secretion inhibition rate (%) Untreated (saline) - Example 28.31 ± 4.1 Comparative example 3.24 ± 1.5

As shown in Table 8, it was confirmed that the secretion of histamine from the intraperitoneal mast cells induced by the compound 48/80 was inhibited by 28% only by the mixed element and LHCCP. Therefore, it was confirmed that treatment of mixed elements and LHCCP can be suppressed by treating atopic dermatitis or other skin diseases involving immune and inflammatory reactions. On the other hand, even when each individual element was mixed and processed, it was confirmed that the effect similar to the above can be acquired.

Experimental Example 18 Measurement of IL-6 Concentration and IgG2a Concentration

Composition 1 and Comparative Example composition obtained in Example 1, respectively, was applied to the skin of the neck (1 mg / day) to NCNga mice. NCNga mice treated with the composition according to Example 1 and Comparative Example composition for 12 weeks were anesthetized with ethyl ether, and blood was collected by cardiac puncture to separate serum, and then serum was purified using Elisa kit. IL-6 was quantified, and the concentration of antibody protein IgG2a in serum was measured using a Map-Based Mouse Ig Isotyping Kit (PharMingen, San Diego, Calif). It was. The unit is μg / ml.

As can be seen in Table 9, the composition treatment group according to the present invention showed significantly lower blood IL-6 concentration and IgG2a concentration than the control group. Therefore, the composition according to the present invention was reaffirmed that it is effective for atopic dermatitis or other skin diseases accompanied by an inflammatory reaction.

Experimental Example 19: IL-13 Concentration Measurement

Composition 1 and Comparative Example composition obtained in Example 1 were skin coated (1 mg / day) on the neck area of NCNga mice, respectively. Thereafter, the facial and neck portions of the NCNga mice treated with the composition according to Example 1 and the comparative example composition were collected for 12 weeks, and then 1 g of skin tissue was removed, washed with DMEM medium, mixed and chopped. It was then incubated in a petri dish with DMEM culture medium containing 10% FBS. After 7 days, the culture supernatant was removed and replaced with DMEM medium containing fresh 10% FBS. After culturing for 7 days, the culture supernatant was separated, and the concentration of IL-13 in the culture was measured using an ELISA kit. The unit is μg / ml.

Average Standard Deviation Example 98.7 24 Comparative example 218.6 30.1

As can be seen in Table 10, the tissue culture solution of the composition treatment group according to the present invention showed an IL-13 concentration in the culture medium is significantly lower than the tissue culture solution of the control group. Therefore, the composition according to the present invention was reaffirmed that it is effective for atopic dermatitis or other skin diseases accompanied by an inflammatory reaction.

Experimental Example 20 Measurement of Ceramide Formation

The production capacity of ceramide, one of the components of intercellular lipid, was measured. The composition obtained in Example 1 and the comparative example composition were each skin-coated (1 mg / day) on the neck of NCNga mice. Subsequently, the skin tissue of the experimental animals treated with the composition and vehicle for 7 days was sectioned with an 8 mm punch so that the dermis went down in a Petri Dish containing PBS solution containing 0.25% Trypsin. After immersion, it was left at room temperature for 120 minutes. The epidermal layer was separated from the tissue, washed with distilled water, and then drained using a filter paper, and weighed. Almost dried keratin was added to 5 ml of a Bligh-Dyer solution (methanol: chloroform: water = 4: 2: 1.6), left for 24 hours after stirring, the suspension was collected, and the precipitate containing the stratum corneum was again collected. To the mixture was added 4 ml of a mixture of chloroform and methanol (chloroform: methanol = 2: 1), followed by stirring, followed by filtration with a filter paper together with the suspended solids collected separately. 6 ml of distilled water was added to the filtrate and stirred, and only the lower layer was centrifuged at 2,000 rpm for 10 minutes, dried with nitrogen gas at 35 ° C, and mixed with chloroform and methanol (chloroform: methanol = 2: 1) in a predetermined amount. Melted and stored. A certain amount was deposited on a silica gel TLC (silica gel TLC) plate and developed with a developing solvent having a composition ratio as shown in Table 11. After the TLC plate was developed, the size of each band was measured.

Developing solvent composition (ml) Solvent movement distance (cm) Primary Chloroform 50
Acetone 20
Methanol 30 5 Secondary Chloroform 75
Acetone 5
Methanol 25 7 Third Chloroform 72
Ether 6
Ethyl acetate 20
Methanol 2 9

The ceramide formation amount of each treatment group converted to the ceramide generation amount of the untreated group as 1 is shown in FIG. 13. It can be seen that the amount of ceramide produced increased by 45% in the composition-treated group obtained in Example 1 compared to the untreated group or the comparative example-treated group. From the above results, it can be seen that the composition according to the present invention can increase the amount of ceramide produced to enhance the barrier function of the skin to minimize physical stimulation to the stratum corneum. Therefore, it was confirmed that the composition of the present invention containing the mixed element and LHCCP can be used for the improvement and treatment of skin diseases caused by atopic dermatitis or damage to the skin barrier.

Experimental Example 21 Measurement of Wound and Laceration Effects in Animals

The experimental animals were 8 week-old ICR male rats (30 ± 3 g) and fed freely with general solid feed (Samyangsa) and water before the start of the experiment. (20 ~ 24 ℃, humidity 60 ~ 80%) preliminary breeding period was given. After the adaptation period, the hairs of the experimental animals were removed and wounds were made using a razor with a length of 1 cm, a width of 0.01 cm, and a depth of 0.5 cm, and lacerations were made using a round iron rod in an area of 1 cm in diameter. The experimental animals were divided into the control group, the experimental group, and the madecassol treatment group on the market. Each group maintained 24 hours a day, divided into 12 hours of light and cancer. The compositions prepared according to Example 2 and Comparative Example were applied to the wound site twice daily for a fixed amount (1 ml) in the morning and evening at regular times. All experiments were conducted to stabilize rats without testing when cancerous, and recovery period was allowed for 24 hours before the experiment.

The results are shown in Fig. As shown in Figure 14, when treated with the composition of Example 1 and madecassol, the effects of wound and laceration over time was confirmed. However, when treated with the composition of Example 1, the effect is much faster than when treated with madecassol, in particular, it was confirmed that the effect is very fast from 5 days after the composition treatment. From the above results, it was confirmed that the damage or defect of the skin to external physical stimuli can be improved or cured by using the composition according to the present invention.

Experimental Example 22: Animal Skin Tissue Observation

After sacrificing the experimental animal of Experiment 21 by cervical dislocation method, the skin was separated to remove foreign substances as much as possible with PBS (phosphate buffered saline), and the experimental site was cut out with scissors and used in the following experiment. The separated skin was placed in 10% formaldehyde and fixed for one day, cut into 10 mm 3, infiltrated with an autopenetrator for 12 hours, a paraffin block was made, and cut into 4 μm thickness using a thinner. It was then stained according to hematoxylin & eosin staining conditions. Reading and photography were performed at 100 times using an optical microscope.

The results are shown in Fig. As shown in Figure 15, the experimental group treated with the composition of Example 1 and the control group treated with Madecassol can be seen that there is a significant difference in wound and laceration treatment. In the case of the composition of Example 1, the wound was almost cured, and the control group and the madecassol treatment group may be said to be in the process of healing with inflammation. This indicates that the composition of Example 2 is more effective for treatment. Therefore, it was again confirmed that the damage or defect of the skin to external physical irritation can be improved or cured by using the composition according to the present invention.

Experimental Example 23: Skin Exfoliation Experiment

The quality of the Simple Monadic Test method was evaluated in 20 women aged 20 to 35 years through a questionnaire asking about the degree of exfoliation after using the composition of Example 4 in the form of a product and using it for 15 days. It carried out and showed as a result of the 5-point scale of following Table 12.

score Exfoliation effect 5 Excellent for exfoliating skin 4 Excellent for exfoliating skin 3 Common to exfoliation 2 Poor to exfoliate skin One Very poor at exfoliating skin

division Example Comparative example Exfoliation effect 4.31 2.21

As shown in Table 13, the composition containing the mixed element and LHCCP was superior to the exfoliation ability compared to the comparative example.

Experimental Example 24: insect bites

Experiments were performed on 20 adult men and women with wounds caused by mosquitoes and other insects. The composition of Example 5 and the composition of Comparative Example were randomly divided, and the insects were bitten and applied, thereby obtaining the results as shown in Table 14 below.

-: No symptoms, +: Not severe, ++: A little severe,

+++: Severe, ++++: Very bad.

As shown in Table 14, the composition containing the mixed element and LHCCP was superior to the itching and inhibiting erythema production compared to the comparative composition. From the above results, it can be seen that the immune response and inflammatory response by the insect are inhibited by the composition according to the present invention.

Experimental Example 25: skin irritation test and toxicity test

In all of the above experiments, no skin irritation was observed in animals or humans, and 20 4-week-old mice (ICR) were freely fed with water containing mixed elements (100 ng) and LHCCP (10 ㎍) for 2 months. In case of death, no animals died, and as shown in FIG. 16, the body weight was increased as in the case of not feeding the mixed element and LHCCP.

Figure 1a is a diagram showing the effect of promoting cell growth according to the concentration of each component;

Figure 1b is a diagram showing the cell growth promoting effect of the mixed elements and LHCCP mixture;

2 shows the removal of free radicals after treating the present composition;

3 shows the anti-lethal concentration of cells due to hydrogen peroxide damage;

4 is a diagram showing a cell growth recovery effect by treating a mixed element, LHCCP mixture after treatment with hydrogen peroxide;

5 is a diagram showing the activity and lipid peroxidation amount of superoxide dismutase (SOD), catalase (CAT) in cell lines;

6 is a diagram showing the activity and lipid peroxidation amount of superoxide dismutase (SOD), catalase (CAT) in experimental animals;

7 shows TGF, EGF, PDGF and VEGF expression in cell lines;

8A is a diagram showing the expression of TGF, EGF, PDGF and VEGF in experimental animals due to wounds;

8B is a diagram showing TGF, EGF, PDGF and VEGF expression in experimental animals due to laceration;

9 is a view showing the expression level of PKC to determine the anti-inflammatory effect in the cell line;

10 is a view showing the expression level of PKC to determine the anti-inflammatory effect in experimental animals;

11 is a view showing the antimicrobial activity of the mixed element and LHCCP mixture;

12A is a diagram showing the percutaneous water loss of experimental animals;

12B is a diagram showing the transdermal moisture content of experimental animals;

13 is a view showing the ceramide generating ability in the experimental animal;

14 shows the effects of wound and laceration on animals;

15 is a diagram showing the staining of the skin tissue of the experimental animal;

16 is a view showing the toxicity test of the experimental animals.

Claims (29)

As an active ingredient, Iii) a mixture of lycopene, hexacosanol, catechin, propolis and cordycepin; And Ii) Cerium (Ce), Praseodymium (Pr), Promethium (Pm), Europium (Eu), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Erbium (Er), Thulium (Tm), Ytterbium (Yb) ), One or more rare earth elements selected from scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu), or salts or oxides thereof: Containing, anti-inflammatory, antioxidant or antibacterial cosmetic composition. delete delete delete delete The method of claim 1, Lycopene: hexacosanol: catechin: propolis: cordycepin is 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5, the anti-inflammatory, antioxidant or antibacterial cosmetic composition . The method of claim 1, V) anti-inflammatory, antioxidant or antibacterial cosmetic composition having a weight ratio of 1: 1 to 100: 1. The method of claim 1, Anti-inflammatory, antioxidant or antibacterial cosmetic composition containing the active ingredient in an amount of 0.0001 to 10% by weight relative to the total weight of the cosmetic composition. The method of claim 1, The lycopene, hexacosanol, catechin, propolis and cordycepin are naturally-occurring or artificially synthesized, anti-inflammatory, antioxidant or antibacterial cosmetic composition. The method of claim 1, The rare earth element, or salts or oxides thereof is obtained in nature, anti-inflammatory, antioxidant or antibacterial cosmetic composition. The method of claim 10, The rare earth element, or a salt or oxide thereof is contained in deep soil, loess, red soil or deep sea water, anti-inflammatory, antioxidant or antibacterial cosmetic composition. The method of claim 1, The cosmetic composition is used for atopic dermatitis, wounds or lacerations, acne, keratin, insect bites, for use in restoring or moisturizing the skin barrier, anti-inflammatory, antioxidant or antibacterial cosmetic composition. The method of claim 1, The cosmetic composition is an anti-inflammatory, antioxidant or antibacterial cosmetic composition for use as a cream, lotion or soap. The method of claim 1, The cosmetic composition is an anti-inflammatory, antioxidant or antibacterial cosmetic composition for applying to humans or breeding or pets. As an active ingredient, Iii) a mixture of lycopene, hexacosanol, catechin, propolis and cordycepin; And Ii) Cerium (Ce), Praseodymium (Pr), Promethium (Pm), Europium (Eu), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Erbium (Er), Thulium (Tm), Ytterbium (Yb) ), One or more rare earth elements selected from scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu), or salts or oxides thereof: Containing, anti-inflammatory or anti-bacterial pharmaceutical composition. delete delete delete delete 16. The method of claim 15, Lycopene: hexacosanol: catechin: propolis: cordycepin is 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5, the anti-inflammatory or antibacterial pharmaceutical composition. 16. The method of claim 15, The anti-inflammatory or antibacterial pharmaceutical composition, wherein the weight ratio of iii) and ii) is from 1: 1 to 100: 1. 16. The method of claim 15, Anti-inflammatory or anti-bacterial pharmaceutical composition containing the active ingredient in an amount of 0.0001 to 10% by weight based on the total weight of the pharmaceutical composition. 16. The method of claim 15, The lycopene, hexacosanol, catechin, propolis and cordycepin are naturally-occurring or artificially synthesized, anti-inflammatory or antibacterial pharmaceutical composition. 16. The method of claim 15, The rare earth element, or salts or oxides thereof is obtained in nature, anti-inflammatory or anti-bacterial pharmaceutical composition. 25. The method of claim 24, Rare earth element, or salts or oxides thereof is contained in ocher, clay, red soil or deep sea water, anti-inflammatory or anti-bacterial pharmaceutical composition. 16. The method of claim 15, The pharmaceutical composition is an anti-inflammatory or anti-bacterial pharmaceutical composition for use in atopic dermatitis, acne, keratin, skin barrier recovery or moisturizing. 16. The method of claim 15, The pharmaceutical composition is an anti-inflammatory or antibacterial pharmaceutical composition for transdermal or oral administration. 28. The method of claim 27, The pharmaceutical compositions are anti-inflammatory or anti-inflammatory, formulated into ointments, patches, sprays, tablets, pills, powders, sachets, elixirs, suspensions, emulsions, solutions, syrups, or soft or hard capsules. Bacterial Pharmaceutical Compositions. 16. The method of claim 15, The cosmetic composition is an anti-inflammatory or anti-bacterial pharmaceutical composition for application to humans or breeding or pets.

Images