KR20170094903A - Composition containing complex extracts including Veratrum nigrum var. ussuriense, Juglans mandshurica, Rodgersia podophylla and Chaenomeles sinensis with antioxidant activity or whitening - Google Patents

Abstract

The present invention relates to the use of V eratrum There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla , and Chaenomeles Sinensis , or a fraction thereof, as an active ingredient. The present invention also relates to a cosmetic composition, a food composition, an external composition for external use, a composition for external application for skin, and a pharmaceutical composition.
The compositions of the present invention are excellent in DPPH radical scavenging activity, excellent in efficiency of inhibiting tyrosinase activity, and can be used for antioxidant or whitening purposes.

Description

TECHNICAL FIELD The present invention relates to a composition for antioxidant or whitening comprising a complex extract of phalaenopsis sp. ussuriense, Juglans mandshurica, Rodgersia podophylla and Chaenomeles sinensis with antioxidant activity or whitening}

The present invention relates to the use of V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) or fractions thereof as an active ingredient, to a cosmetic composition for antioxidant or whitening, a food composition, a quasi-drug composition, a composition for external application for skin, and a pharmaceutical composition.

All organisms, including humans, experience life and aging, two biological changes throughout their lives. Growth refers to an increase in the size or function of an individual, while aging refers to a phenomenon in which the size or function of an individual decreases or declines, and growth and aging can occur at the same time. However, aging phenomenon becomes more prominent with increasing time and age, and cell division ability and metabolic activity gradually decrease, so that the organism can not become ill or perform physical and functional smooth activities. The mechanism of senescence is divided into genetic program theory, somatic mutation theory, error fracture theory, free radical theory, endocrine theory by specific hormone action, immune disruption due to impaired immune surveillance, stress theory, lipofuscin and lipid peroxidation There are various aging related theories such as accumulation of wastes based on the accumulation of collagen, and crosslinking (binding) following the progress of crosslinking of tissue collagen fibers, but there is no clear explanation yet.

Among the various aging phenomena such as decline of hearing, smell, taste, reduction of lung capacity, weight loss of organs, aging phenomenon, which is generally felt and felt most directly by people, is the skin aging phenomenon. The most supported theory about the aging phenomenon occurring in the skin tissue is the free radical theory. According to the theory, free radicals are generated in the living body by metabolic reaction, ultraviolet ray, soot and environmental hormone, and this free radical As the barrier is destroyed, lipids, proteins, polysaccharides and nucleic acids, which are the main constituents of skin, are oxidized and consequently promote the aging process of skin cells and tissues. In other words, skin is oxidatively stressed by radicals such as superoxide radicals (O ^2- ) and hydroxyl radicals (OH) and non-radicals such as hydrogen peroxide (H ₂ O ₂ ) . In particular, when proteins are oxidized, collagen, hyaluronic acid, elastin, proteoglycan, fibronectin, etc., which are the connective tissues of the skin, are severed, resulting in severe hyperinflammation reaction and decreased skin elasticity If this becomes worse, DNA mutation leads to mutation, cancer induction, and immune function deterioration. Therefore, in order to prevent skin aging, it is necessary to prevent skin damage by eliminating free radicals caused by various causes, and already damaged cells need to be regenerated and reproduced by active metabolism.

On the other hand, human skin color largely depends on the amount of melanin pigment contained in skin cells. People with a lot of melanin pigments have brown or black skin, while those with very low melanin pigment cause vitiligo. Melanin pigment is produced from tyrosine by tyrosinase in pigmented cell called melanocyte which exists in basal membrane of skin. Melanin pigment protects skin from excessive ultraviolet rays, so it plays an important role in suppressing skin damage and skin cancer caused by ducts. However, when melanin is excessively produced by daylight, hormone changes, inflammation, medicines, etc., the pigment of the skin is deposited, which causes cosmetic problems. For example, skin pigmentation of the skin is caused by an increase in the amount of melanin pigment, which means that the production of melanin pigment is promoted or the number of melanocytes is increased.

Accordingly, in recent years, various whitening cosmetics and medicines for preventing and improving such problems have been developed and marketed. Currently, in the development of a whitening agent for skin cosmetics, a method of decolorizing the resulting melanin pigment and a method of inhibiting the activity of tyrosinase, an enzyme that forms a melanin pigment, are known. However, it is known that the whitening agent using tocopherol or the like, which is used for reducing the melanin pigment, has little discoloration effect on the melanin pigment. Accordingly, inhibitors that inhibit the activity of tyrosinase and inhibit the production of melanin pigment have been attracting attention.

Tyrosinase is an enzyme that catalyzes the oxidation of monophenols and is contained in the melanocytes of higher animals. Tyrosine is oxidized by this enzyme and melanin pigment is produced through a series of chemical reactions and oxidation. This melanin pigment is brown or black, which absorbs excess light in vivo, which adversely affects skin beauty. In view of the fact that the activity of tyrosinase is inhibited, the production of melanin pigment can be inhibited. Thus, in the field of the conventional cosmetics, natural plant extracts and the like are used as inhibitors of tyrosinase activity as natural whitening extracts.

Under these circumstances, the inventors of the present invention have made efforts to develop a plant extract that has superior radical scavenging ability and can effectively inhibit tyrosinase activity, as compared with the conventional plant extract. As a result of intensive efforts, the inventors of the present invention have found that a combination of spruce, It was confirmed that the extract had an excellent radical scavenging ability and could effectively inhibit tyrosinase activity, thus completing the present invention.

Korean Patent Publication No. 10-1998-077719 (published on November 16, 1998).

One object of the present invention is to provide a method of < RTI ID = 0.0 > There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

Another object of the present invention is to provide There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a device There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a device There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a device There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla , and Chaenomeles Sinensis , or a fraction thereof, as an active ingredient.

Hereinafter, the present invention will be described in more detail.

In order to achieve the above object, the present invention In some embodiments, a participation (V eratrum There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

The cosmetic composition of the present invention as an active ingredient, with the participation (V eratrum There is nigrum . ussuriense , Juglans mandshurica , Rodgersia podophylla , and Chaenomeles sinensis .

The above roads are native to the northern part of Korea and north of Gyeongsangbuk-do, and are distributed in Russia and China. A perennial plant called scientific name, also known as a big journey, Wang journey that grows under the trees on the mountain is Veratrum nigrum , and more specifically V eratrum There is nigrum . It is ussuriense . The stem is 1-1.5cm high, and the old leaves are covered with net-shaped fibers at the bottom, the rootstock is short, and the stem of beard is thick. The leaf is in the lower part of the trunk, and the leaf at the bottom is wide oval, 40cm long, 10cm wide, pointed at the end, narrowed downward to connect to the sheath, wrapped around the stem, Lt; / RTI > Flowers bloom in July-September, 6 pieces of crustacean, with long oval shape and blunt ends. On the back of the outer sculpture, there is a dense white hairs. The flower is 1cm in diameter, dark purple, 6 stamens, about 1/2 of the length of the hymen, and the stigma divides into 3 pieces. The ovary is ovate and hairy on the lower part, and the style is divided into three branches and tilted backward. The fruit is a three-angular oval-shaped capillary, purple, about 1 cm in length, and spreads in three branches.

In the present invention, the cosmetic composition of the present invention can be applied to an extract obtained by drying and crushing a participating pathway into powder, and it can contain leaves, stems, stem barks, branches, bark, roots, Specifically, it may be a leaf, a stem, a stem shell, a branch, a bark, a flower, or all of them, which corresponds to the ground part of the participant except the root.

The spiny tree is also known as 楸 子 木 (楸 子 木), and the fruit is called 楸 子 (楸 子), the scientific name is Juglans It is mandshurica . It grows on the sides of the mountain and is about 20cm high. The bark is dark gray and bursts vertically. Leaves are odd numbered compound leaf, small leaves are 7 ~ 17 pieces. Long elliptical or oval oval, 7 ~ 28cm long, 10cm wide. There is a sawtooth, the front side has fine hairs but gradually disappears, and the back side has hairy or no hairs. Flower is bloomed in April as monogenous flower. Male flower is bloomed from the side branch of last year of 10 ~ 25cm with new leaf in May ~ June, and the female flower ear is 6 ~ 13cm long and extends straight from the end of branch , 7 to 10 flowers per ears. Fruit is a nucleus, 4 ~ 8cm long, egg-shaped or elliptical, ripened in September-October. The yellowish green fine hairs are dense, the ends are pointed, and are very hard. Seeds contain a large amount of fat, 55.5 ~ 60.6% fat, rich in nutrients, and unsaturated fatty acids in fat. Seed is used as a medicine to prevent arteriosclerosis. It is a deciduous broad-leaved arboreous tree native to the northwestern part of Korea, such as Sobaeksan and Mt. Soki. It is also distributed in northern China, northeast and Siberia in the former Soviet Union.

In the present invention, the cosmetic composition of the present invention can be applied to extraction by drying and crushing the spruce tree, and may be applied to an extract, and may include leaves, stem, stem skin, branches, bark, roots, And may specifically include leaves, stems, stem barks, branches, bark, flowers or all of them corresponding to the underside of the spruce tree except for the roots, and more specifically, leaves and stems may be used from above .

The above-mentioned gecko debt is also known as a mountain, a sum, a wagon, and the scientific name is Rodgersia Podophylla . I am a perennial herb in the deep mountain shore in the north of the central part. The growth environment is a lot of valley water, the humidity is high and the soil is fertile and grows out of sunlight. Its height is about 1cm. Leaves are alternate phyllotaxis and petiole is long and split into 3 ~ 6 pieces. Small leaves come out of five, large ones are about 50cm in diameter, and the upper ones have 1 to 4 small leaves. The small leaf has irregular sawtooth on the edge in the shape of inverted egg. There are hairs on upper petiole and back petiole. The flower blooms in June, and it is yellowish white. The length of the peduncle is 20 ~ 40cm. There are 10 stamens, longer than calyxes, and 2 stigma. The fruit runs in broad egg shape around August to October, and there are no petals. The calyx is deeply divided into 5 pieces, and the piece is long ovate and white. The rootstock is large and thick. It is distributed in Gyeongsangbuk-do, Gangwon-do, Pyongan, North Hamgyong, North Hamgyong, and Japan.

In the present invention, the cosmetic composition of the present invention can be applied to an extract obtained by drying and crushing a bark beetle with powder, and it can contain leaves, stems, stem barks, branches, bark, roots, flowers or both of them. Specifically, leaves, stems, stem peels, branches, bark, flowers, or all of them corresponding to the underside of the bugle fan except the root.

The quince tree is a tree of Chinese origin, and is widely planted in the central and southern regions. Its scientific name is Chaenomeles Sinensis . The soil is deep and drainage is good and likes the fertile place. They are planted for ornamental, fruit or bonsai. The bark is purple-brown and shiny. The bark of the old tree blooms in the spring and falls, and the place of the bark is bluish. The height reaches 10m. There are hairs on young branches and there is a dark brownish shine of two years. Leaves are alternate phyllotaxis ovate or long oval. There is a sawtooth on the upper edge of the leaf, a line on the bottom, and the cotyledon drops early. The flower has five rounded petals. In May, one flower blooms at the end of the twig. It is light red with a diameter of 2.5 ~ 3cm. The petal is shaped like an inverted egg and the tip is concave. Fruits are oval or inverted egg, 10 ~ 20cm in length, 8 ~ 15cm in diameter, and woody is developed. It ripens in yellow in September and has a good aroma but strong acidity. It is used as a medicinal material for the food of fruit and contains a large amount of tannin. Jinhae, geomdan, governor, and pain relief. Applicable diseases include pertussis, asthma, bronchitis, pneumonia, pleuritis, diarrhea, neuralgia, myalgia and anemia.

In the present invention, the cosmetic composition of the present invention can be applied to an extract obtained by drying and crushing a quince tree and pulverizing the quince tree. The cosmetic composition may contain leaves, stem, stem skin, branch, And may specifically include a leaf, a stem, a stem skin, a branch, a bark, a flower or all of them corresponding to a ground part of a quince tree except for a root. More specifically, a stem may be used from above.

In the present invention, the term "above ground" means a portion of the upper surface of the earth about the earth in the plant. That is, it refers to the upper surface of the ground excluding roots, which includes leaves, stems, stem barks, branches, bark, flowers, or all of them except roots.

The term "complex extract" in the present invention refers to a form of an extract obtained by mixing natural products such as plants, followed by extraction with one or more solvents, or a mixture of extracts obtained by extracting each natural product with a solvent. In the present invention, the compound extract may be a mixture of extracts of Solanaceae, Spodoptera, Bombyx mori, Leucocephalus and Sclerotinia with an extractive solvent, have.

The term "extract" in the present invention refers to an extract obtained by extracting the extract itself, such as an extract obtained by extraction, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, a controlled preparation or purified product of the extracted solution, , ≪ / RTI > The extract of the present invention can be extracted from natural, hybrid, or mutant plants of the respective plants, and can also be extracted from plant tissue cultures.

In the extraction of the present invention, the extraction method is not particularly limited, and extraction can be carried out according to a method commonly used in the art. Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.

Drying of the extract in the present invention can be carried out by a known method insofar as the useful components from the collected plants are not destroyed, and can be carried out, for example, by a natural drying method in shade. In addition, the crushing can be sufficient to break up the crushed to such an extent that the useful components of the plant can be sufficiently extracted in the subsequent extraction process, and can be pulverized. The drying and crushing steps may be carried out in reverse order or repeatedly as required.

To participate in the present invention (V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles The type of extraction solvent used to extract Sinensis is not particularly limited and any solvent known in the art can be used. In the present invention, the complex extract may be obtained by extracting with water, a C ₁ to C ₄ lower alcohol or a mixed solvent thereof. Further, non-limiting examples of the extraction solvent include water; C ₁ to C ₄ lower alcohols such as methanol, ethanol, propyl alcohol and butyl alcohol; Polyhydric alcohols such as glycerin, butylene glycol and propylene glycol; And hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and dichloromethane; Or a mixture thereof. Specifically, water, a lower alcohol, 1,3-butylene glycol, and ethyl acetate may be used alone or in admixture of two or more.

To participate in the present invention (V eratrum There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ), more specifically, water, ethanol, methanol can be used. Using the above solvent, V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla , and Chaenomeles Sinensis , followed by one or more extractions to prepare a complex solvent extract. The dry extract obtained by vacuum distillation of the solvent extract, followed by lyophilization or spray drying can be prepared have. In a specific example of the present invention, water and ethanol were used as extracting solvents to prepare a combined extract of Phellinus linteus, Spodoptera exigua, .

The extraction can be carried out by extracting a mixture (complex) obtained by mixing the plant dry matter, There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) can be prepared by extracting a mixed sample (mixture) containing the active ingredient at a weight ratio of 1.5 to 2.5: 1.5 to 2.5: 0.5 to 1.5: 0.5 to 1.5, and specifically 1.8 to 2.2: 1.8 to 2.2 : 0.8 to 1.2: 0.8 to 1.2 in weight ratio. In this case, it is possible to produce a complex extract (mixture) containing the extract of the present invention which has antioxidative and whitening activity at the same time as that of a single extract, Can be obtained.

The extraction is carried out at a temperature of from 10 to 80 ° C, specifically from 15 to 50 ° C, using a solvent having a volume of from 1 to 10 times by volume, specifically from 1 to 5 times, To 30 days, more specifically, 12 hours to 18 days. The process of extracting the crude extracts in a liquid phase one to five consecutive times, including the above-mentioned dried and crushed products, . ≪ / RTI >

In order to remove suspended solid particles, the complex extracts extracted in the present invention may be filtered by filtration using, for example, nylon, filter paper, etc., or filtered using freeze filtration or the like, It can be dried and used.

The liquid crude extract may be separated from the dry matter of the plant by vacuum filtration or the like, followed by concentration or drying. For example, the liquid crude extract may be concentrated in a vacuum rotary condenser at 20 to 100 ° C, preferably 40 to 70 ° C, and the liquid extract may be dried to obtain a powdered complex extract have. The concentrated or powdered complex extract may be used in water, alcohol, dimethyl sulfoxide (DMSO), or a mixed solvent thereof, if necessary.

In an embodiment of the present invention, 1 kg of a completely mixed sample, which is a mixed sample of 2: 2: 1: 1, is mixed with 9 liters of ethanol and 15 At 37 ° C for 14 days, followed by filtration and concentration under reduced pressure to obtain a dried complex extract (Example 2).

The term "fraction " as used herein means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.

The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. Non-limiting examples of such fractionation methods include, but are not limited to,eratrum nigrum there is. ussuriense), Spruce (Juglans mandshuricaHowever,Rodgersia Podophylla), And quince treesChaenomeles Sinensis) Is extracted and the obtained complex extract is treated with a predetermined solvent to obtain fractions from the extract.

The kind of the solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When alcohol is used in the fraction solvent, C ₁ to C ₄ alcohols can be specifically used.

The term "antioxidant" used in the present invention means an antioxidant action. The human body has a balance between a prooxidant and an antioxidant, but due to various factors, Becomes unbalanced and tilting toward oxidation promotes oxidative stress leading to potential cellular damage and pathological disease. Reactive oxygen species (ROS), which is a direct cause of oxidative stress, is unstable and highly reactive. It reacts easily with various bio-materials, attacks irreversible damage to cells and tissues, Cytotoxicity and carcinogenesis. Active nitrogen species (RNS) such as NO, HNO ₂ , and ONOO ^- are produced by the immune response of macrophage neutrophils and other immune cells during inflammatory reaction, and ROS is also produced. Such active oxygen oxidizes and destroys cells in the body, thereby exposing them to various diseases. In addition, the antioxidant has a function of inhibiting oxidation of cells due to highly reactive free radicals or reactive oxygen species (ROS) according to oxidative stress caused by intracellular metabolism or ultraviolet rays And eliminating free radicals or reactive oxygen species, thereby reducing damage to the cells.

To participate in an embodiment of the present invention (V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp debt (Rodgersia Podophylla ), and quince trees ( Chaenomeles The concentration of the IC ₅₀ (concentration of the sample which scavenges 50% of the DPPH free radical) of the ethanol extract of Sinensis was 11.4 / / ml, which was similar to that of the positive control vitamin C known to have high antioxidant activity. Antioxidant activity was excellent. In addition, it was confirmed that DPPH free radical scavenging ability was remarkably superior to vitamin C, which is a positive control group, at 100 μg / ml and 20 μg / ml of the combined extract, and as a result, the combined extract of spruce, It has been confirmed that it has excellent antioxidative activity through inhibition of free radical which accelerates the skin aging process. Accordingly, it was confirmed that the compound extract of the present invention can be applied to cosmetic compositions for antioxidation. In addition, as a part of the present invention, the combined extracts of the spruce tree, the spruce tree, and the spruce tree include the extracts of the spruce tree, the spruce tree, the extract of the spruce tree, the extract of the spruce tree, Compared with the complex extract of the goby drapery, it has an excellent antioxidative activity by inhibiting free radicals promoting the aging process of the skin, and exhibits an effect of remarkably lowering the degree of aging process and skin damage by antioxidant activity (Experimental Example 1).

As used herein, the term "whitening" refers to a method of increasing the lightness of skin with reduced brightness due to excessive pigment such as melanin or keeping the brightness of skin at a certain level, Skin, and the like. Specifically, it may mean skin whitening. For the purpose of the present invention, the whitening is carried out by means of inhibiting tyrosinase activity, which promotes the synthesis of melanin formed in the skin by the ethanol combined extract of spruce, spruce, But is not limited to.

Melanin is a pigment that is widely distributed in living organisms such as skin, hair and eyes. Melanin is synthesized in Melanosome in Melanocyte of human skin. Tyrosine (tyrosine) Melanin is biosynthesized by the oxidation and polymerization reaction which is converted to DOPA (3,4-dihydroxy-phenylalanine) or DOPA quinone (Dopaquinone) as a starting material. Biosynthesized melanin increases resistance to skin irritation such as ultraviolet rays, but since excessive melanin synthesis causes pigmentation such as spots, freckles, and black spots, tyrosinase activity measurement is regarded as an important indicator of skin whitening effect have.

In one embodiment of the present invention, the IC ₅₀ (concentration of a sample inhibiting 50% inhibition of tyrosinase activity) of the combined extract of P. vivax, P. forest, The amount of tyrosinase was significantly lower than that of arbutin, and the ability to inhibit the activity of tyrosinase was 5 times higher than that of arbutin. In addition, it was confirmed that tyrosinase activity was significantly lower in the positive control group than arbutin at the concentrations of 100 μg / ml and 20 μg / ml in the combined extracts of P. thunbergii, P. japonicus, It was confirmed that tyrosinase activity was significantly lower than that of arbutin at a concentration of 20 占 퐂 / ml and remarkably high efficiency of inhibiting tyrosinase activity was observed.

In addition, as a result of participation of the present invention, the combined extracts of the spruce tree, the spruce tree, and the spruce tree can be used as extracts of the spruce tree, Compared with the complex extract, the tyrosinase activity, which plays a key role in the melanin biosynthesis process, is suppressed to a remarkably high level, thereby effectively inhibiting the production of melanin pigment, thereby preventing skin aging and whitening effect (Experimental Example 2). That is, the complex extract of the present invention has an excellent inhibitory activity on the activity of tyrosinase, effectively inhibiting the production of melanin, and can be applied to a cosmetic composition for whitening.

In addition, it was confirmed that the combined extracts of spruce, decanter, and quercetin could be applied simultaneously for antioxidative and whitening purposes (Examples 1 and 2)

In the present invention, the cosmetic composition may be prepared in various forms, for example, emulsion, lotion, cream (oil-in-water type, oil-in-water type, multiphase), solution, suspension (anhydrous and aqueous) , A gel, a mask, a pack or a powder, and the like. The cosmetic composition of the present invention may contain an acceptable carrier in cosmetic formulations in addition to its effective ingredient. As used herein, the term " acceptable carrier for a cosmetic preparation "refers to a compound or composition that is already known and used in the cosmetic preparation, or a compound or composition to be developed in the future, and which has no toxicity such that the human body can be adapted to contact with skin. The carrier may comprise from about 1% to about 99.99% by weight, specifically from about 50% to about 99% by weight of the composition, based on the total weight of the composition.

However, since the ratio depends on the above-mentioned formulation of the cosmetic composition and its specific application site (face or hands) or its preferable application amount, the ratio is limited in any aspect to the scope of the present invention It should not be.

Examples of the carrier include alcohols, oils, surfactants, fatty acids, silicone oils, humectants, moisturizers, viscosifiers, emulsifiers, stabilizers, sunscreens, coloring agents and perfumes. The compounds / compositions which can be used as the carrier and which can be used as alcohols, oils, surfactants, fatty acids, silicone oils, wetting agents, moisturizers, viscosifiers, emulsions, stabilizers, sunscreens, A person skilled in the art can select and use appropriate substances / compositions.

Specifically, the cosmetic composition can be manufactured to have a formulation selected from a solution suspension, an emulsion, a gel, a cream, a lotion, a powder, a soap, a cleansing, a body wash, a cleansing and a spray, although the formulation is not limited.

The invention in another aspect, a participating (V eratrum There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

In the present invention, the engagement (V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ), complex extracts, fractions, antioxidants and whitening are as described above.

The food composition of the present invention may comprise an acceptable food-aid additive and may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of food.

In the present invention, the term " food " means a natural product or a processed product containing one or more nutrients. Specifically, the term " food " means that the food can be directly eaten through a certain degree of processing. Functional foods, beverages, food additives, and beverage additives. Examples of the food include various foods, beverages, gums, tea, vitamin complex, and functional foods. In addition, the food of the present invention may contain special nutritional foods (eg, crude oil, spirit, infant food, etc.), meat products, fish products, tofu, jelly, noodles (eg, (Such as soy sauce, soybean paste, hot pepper paste, mixed sauce), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods But are not limited to, natural flavors (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages and other health supplement foods. The functional food, beverage, food additive or beverage additive may be produced by a conventional production method.

The term "functional food" as used herein refers to a food group that is imparted with added value to function or express the function of the food by physical, biochemical, biotechnological techniques, etc., or to control the biological defense rhythm of the food composition, Means a food which has been designed and processed so as to sufficiently express the body's control function with respect to the living body. Specifically, it may be a health functional food. In particular, the composition of the present invention is suitable for application as a food composition for antioxidant or whitening. The functional food may include a food-acceptable food-aid additive, and may further comprise suitable carriers, excipients and diluents conventionally used in the production of functional foods.

In the food composition, the amount of the complex extract may be 0.00001 wt% or more, specifically 0.1 wt% or more, and 80 wt% or less, specifically 50 wt% or less, more specifically 40 wt% or less , And when the food is a beverage, it is contained in a proportion of not less than 0.001 g, specifically not less than 0.01 g, not more than 50 g, specifically not more than 10 g, more specifically not more than 2 g based on 100 ml of the total volume of the food But is not limited thereto.

The food composition of the present invention may contain sweetening agents, flavoring agents, physiologically active ingredients, minerals and the like in addition to the active ingredients thereof. Sweetening agents may be used in an amount that sweetens the food in a suitable manner, and may be natural or synthetic. Specific examples of natural sweeteners include corn syrup solids, sugar sweeteners such as honey, sucrose, fructose, lactose and maltose. Flavors may be used to enhance taste or flavor, both natural and synthetic. Specifically, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used. Examples of the physiologically active substance include catechins such as catechin, epicatechin, gallocatechin and epigallocatechin, and vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine and riboflavin. As the mineral, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium and zinc can be used.

In addition, the food composition of the present invention may contain preservatives, emulsifiers, acidifiers, thickeners and the like in addition to the above sweeteners.

Such preservatives, emulsifiers and the like are preferably added in a very small amount as long as they can attain an application to which they are added. The term " trace amount " means, when expressed numerically, in the range of 0.0005% by weight to about 0.5% by weight based on the total weight of the food composition. Examples of the preservative which can be used include calcium sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid). Examples of the emulsifier which can be used include acacia gum, carboxymethyl cellulose, xanthan gum, pectin and the like. Examples of the acidulant that can be used include acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, and phosphoric acid. Such an acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste. Agents that may be used include suspending agents, sedimentation agents, gel formers, bulking agents and the like.

In another aspect, the present invention relates to a method of inhibiting < RTI ID = 0.0 > There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

In the present invention, the engagement (V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ), complex extracts, fractions, antioxidants and whitening are as described above.

The term "quasi-drug product" used in the present invention means products that are less active than drugs, among the products used for diagnosing, treating, improving, alleviating, treating or preventing diseases of human or animal. For example, Quasi-drugs are products that are used for the purpose of treating or preventing diseases of humans or animals, products that are mild or have no direct action on the human body.

 The quasi-drug composition of the present invention can be used as a body cleanser, a disinfectant cleaner, a detergent, a kitchen detergent, a cleaning detergent, a toothpaste, a gauze agent, a wet tissue, a detergent, a soap, a hand wash, a hair cleanser, a hair softener, a humidifier filler, But the present invention is not limited thereto.

In another aspect, the present invention relates to a method of inhibiting < RTI ID = 0.0 > There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

In the present invention, the engagement (V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ), complex extracts, fractions, antioxidants and whitening are as described above.

The term "external preparation" of the present invention is a preparation for external use, and includes external preparation, external preparation, external solution, ointment, warning agent, suppository, etc. The external preparation for skin of the present invention, .

The external preparation for skin according to the present invention may be a parenteral dosage form which is formulated in solid, semi-solid or liquid form by adding a compatible inorganic or organic carrier, excipient and diluent. The preparation for parenteral administration may be a transdermal dosage form selected from the group consisting of drops, ointments, lotions, gels, creams, patches, sprays, suspensions, and emulsions.

Examples of the carrier, excipient and diluent which can be contained in the external preparation include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition for external application for skin according to each formulation may be mixed with other ingredients other than the complex extract of the present invention without any difficulties by those skilled in the art depending on the formulation or use purpose of other external preparations for skin or the like. Effect can occur.

The composition for external application for skin of the present invention may contain 0.0001 to 30% (w / v) of the combined extract of the total composition by weight. If it is contained at less than 0.0001% (w / v), the antioxidant, whitening effect of the skin can not be substantially expected. On the other hand, if it exceeds 30% (w / v), the overall processability of the composition such as solubility in a solvent may be lowered and its use for various purposes such as formulations may be restricted.

In another aspect, the present invention relates to a method of inhibiting < RTI ID = 0.0 > There is nigrum . ussuriense , Juglans mandshurica , Rodgersia Podophylla ), and quince trees ( Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

In the present invention,eratrum nigrum there is. ussuriense), Spruce (Juglans mandshuricaHowever,Rodgersia Podophylla), And quince treesChaenomeles Sinensis), Complex extract, fraction, antioxidant and whitening are as described above.

In the present invention, the pharmaceutical composition may comprise a pharmaceutically acceptable carrier or an additive. In the present invention, the expression "pharmaceutically acceptable" means that the application (subject) does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient. The "carrier" is defined as a compound that facilitates the addition of a compound into a cell or tissue.

The extracts of the present invention may be administered alone or in admixture with any convenient carrier, etc., and such dosage forms may be single-dose or repeated-dose formulations. The pharmaceutical composition containing the extract may be a solid preparation or a liquid preparation. Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like. Solid form preparations may include, but are not limited to, carriers, flavoring agents, binders, preservatives, disintegrants, lubricants, fillers, and the like. Examples of the liquid preparation include water, a solution such as a solution of propylene glycol, a suspension, an emulsion, and the like, but not limited thereto, and it can be prepared by adding a suitable coloring agent, a flavoring agent, a stabilizer, a tackifying agent and the like. For example, powders can be prepared by simple mixing of an extract, which is an effective ingredient of the present invention, with a suitable pharmaceutically acceptable carrier such as lactose, starch, microcrystalline cellulose and the like. The granule is the above-mentioned extract of the present invention; A suitable pharmaceutically acceptable carrier; And a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone and hydroxypropylcellulose, followed by wet granulation using a solvent such as water, ethanol, or isopropanol, or dry granulation using a compressive force . Tablets may also be prepared by mixing the granules with a suitable pharmaceutically acceptable lubricant such as magnesium stearate and then tableting using a tableting machine.

The extract of the present invention may be administered orally or parenterally depending on the disease to be treated and the condition of the subject, an injection (for example, intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant) Rectal, rectal, transdermal, topical, and the like, but the present invention is not limited thereto. May be formulated into suitable dosage unit formulations, including those conventionally used and non-toxic, pharmaceutically acceptable carriers, additives, vehicles according to the route of administration.

The pharmaceutical composition of the present invention may be administered at a daily dose of from about 0.0001 mg / kg to about 10 g / kg, and from about 0.001 mg / kg to about 1 g / kg. However, the dosage may vary depending on the degree of purification of the mixture, the condition of the patient (age, sex, weight, etc.), severity of the condition being treated, and the like. For convenience, the total daily dose may be administered in divided doses several times a day as needed.

When the composition of the present invention is used as a pharmaceutical composition, the content of the complex extract in the composition can be appropriately adjusted to an effective amount capable of exhibiting anti-inflammatory activity according to the symptoms of the disease, the progress of the symptoms, May be 0.0001% by weight or more, specifically 0.001% by weight or more, and 80% by weight or less, and more specifically, 50% by weight or less based on the total weight of the composition.

The composition of the present invention may be used as a < RTI ID = 0.0 > There is nigrum . ussuriense ), spruce ( Juglans mandshurica), imp fan (Rodgersia Podophylla), and pseudocydonia (Chaenomeles Sinensis) combined extract or comprising a fraction as an effective component thereof, and the antioxidant activity and the whitening effect is excellent, a cosmetic composition for antioxidant or whitening, food compositions, quasi-drugs of Composition for skin external application, and pharmaceutical composition.

FIG. 1 is a graph showing DPPH radical scavenging activity of a combined extract of spruce, decanter, and quercetin with participation of the present invention.
FIG. 2 shows the results of evaluation of tyrosinase activity of a combination extract of spruce, decoy, and quercetin with participation of the present invention.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

Example  1: Production of distilled water complex extract of Porphyra spp.

1 kg of mixed dry matter mixed with 2: 2: 1: 1 weight ratio of completely dried, spruce, spruce tree, gibberellike and quince tree was added to 9 liters of distilled water and extracted with hot water for 2 hours for 4 hours. The extract was filtered through 400 mesh filter cloth and concentrated under reduced pressure to obtain 31 g (dry weight).

Example  2: Manufacture of ethanol extract of phalaenopsis spp.

1 kg of a mixed sample, which is a mixture of completely dried, spruce, spruce, decoy, and quince tree at a weight ratio of 2: 2: 1: 1, is placed in 9 liters of ethanol and extracted with a condenser at 15 to 37 ° C for 14 days And repeated three times. The extract was filtered with a No. 2 filter paper of Watts. These plant extracts were concentrated under reduced pressure in a distillation apparatus equipped with a cooling condenser to obtain 35 g (dry weight).

Comparative Example  1: Manufacture of ethanol solely as an extract, in phalaenopsis, gibberellin, or quercetin

1 kg of each of the completely dried, entrained, spruce, goby, or quince tree was added to 9 L of ethanol and extracted in the same manner as in Example 2, followed by filtration and concentration under reduced pressure to obtain respective extracts.

Comparative Example  2: Preparation of Ethanol Composite Extract of Porphyra sp.

 1 kg of a mixed sample obtained by mixing completely dried, entrained, and spruce wood at a weight ratio of 1: 1 was added to 9 liters of ethanol and extracted in the same manner as in Example 2, followed by filtration and concentration under reduced pressure to obtain a combined extract.

Comparative Example  3: Production of ethanol complex extracts of Pseudomonas sp.

 1 kg of a mixed sample, which was a mixture of completely dried, chestnut tree, spruce tree, and goblin, at a weight ratio of 1: 1: 1, was added to 9 liters of ethanol and extracted in the same manner as in Example 2, followed by filtration and concentration under reduced pressure to obtain a combined extract.

Experimental Example  One: Comparative Example  1 to 3, and Example  2 extracts DPPH Scatters  Evaluation (antioxidant activity)

The dry extract of the spruce tree, the bark beetle or the quince tree, the dry extract of the spruce tree prepared in Comparative Example 2, and the ethanol extract of the spruce tree prepared in Comparative Example 1, The combined extracts of the ethanol extracts of the dry, participating, spruce, and omnivorous buds, and the dry, participating, spruce, gibberellate, and ginseng wood extracts prepared in Example 2 were suspended in methanol at a concentration of 100 μg / To form a sample solution, which was then diluted with DMSO.

DPPH reagent (1-diphenyl-2-picryl-hydrazyl) of 5 x 10 ^-4 M was mixed with 100 μl of each sample solution in a 96-well plate, stirred for 1 minute, reacted in an incubator at 25 ° C for 30 minutes And the absorbance was measured at 517 nm using a microplate counter. Vitamin C (100 μg / ml) was used as an experimental control, and the experiment was repeated four times.

The DPPH radical scavenging activity was evaluated by measuring the absorbance of the single extract of Comparative Example 1, the complex extract of Comparative Examples 2 and 3, the compound extract of Example 2 and the control (Control). The results are shown in Table 1 and FIG. 1 Respectively.

In order to evaluate DPPH radical scavenging ability, the sample composition of Blank, control, and experimental group (extract) used in the experiment is as follows.

Blank (2 wells): 100 [mu] l 100% MeOH

Control (2 wells): 100 μl of 100% MeOH, 100 μl of DPPH

Extract Sample: 2 μl of sample, 100 μl of 100% MeOH, 100 μl of DPPH

division DPPH  Concentration of sample with 50% free radical scavenging (IC ₅₀  : [Mu] g / ml) Comparative Example 1 As a participant > 40 Spruce tree 12.2 Goblin debt 12.3 Quince tree 15.6 Comparative Example 2 Participation by: Phalaenopsis
(1: 1) 24.9 Comparative Example 3 Participation road: spruce tree: goblin debt
(1: 1: 1) 22.4 Example 2 Participation road: Spruce tree: Beetle Debt: Fruit tree
(2: 2: 1: 1) 11.4 Vitamin C (positive control) 11.2

The antioxidant power of the extracts was calculated by the vitamin C standard curve and the IC ₅₀ was calculated based on the dose response curve. The degree of extinction of the sample was expressed as ㎍ vitamin C equivalents per 100 mL (㎍ vitamin C equivalents per 100 mL) considering the correlation with the vitamin C standard curve.

As shown in Table 1, the IC ₅₀ value of the compound extract of Example 2 was 11.4 占 퐂 / ml, which was significantly lower than that of the single extract of Comparative Example 1, the compound extract of Comparative Example 2, and the compound extract of Comparative Example 3 Respectively. This value was similar to that of positive control vitamin C, which is known to have a high antioxidant activity. Thus, the compound extract of Example 2 has the highest antioxidative activity.

1 is a graph showing DPPH free radical scavenging activity (%) according to the concentration of the complex extract prepared in Example 2 of the present invention. As shown in FIG. 2, the DPPH free radical scavenging ability was remarkably superior to vitamin C, which is a positive control group, at 100 占 퐂 / ml and 20 占 퐂 / ml of the combined extract of spruce, Respectively.

In addition, in the case of the extract obtained from the above-mentioned Comparative Example 1, the extract of Solanaceae, the spruce tree, the gibberellin, the extract of Prunus mume, the compound extract of Comparative Example 2 and the compound extract of Comparative Example 3, the concentration of the sample which scavenges the DPPH radical by 50% Was higher than that of the compound extract of Example 2, indicating that the compound extract of Example 2 had a higher antioxidant activity than the extract of Example 2.

Accordingly, the compound extract of the spruce tree, the spruce tree, and the spruce tree is considered to be the most effective means of the present invention. The extract of the spruce tree, the spruce tree, Compared with the complex extract of the ginseng extract, it has an excellent antioxidative activity by inhibiting free radical which accelerates the aging process of the skin. Therefore, it can exhibit the effect of lowering the aging process and skin damage by antioxidant activity.

Experimental Example  2: Comparative Example  1 to 3, and Example  2 inhibited tyrosinase activity (whitening effect)

The dry extract of the spruce tree, the bark beetle or the quince tree, the dry extract of the spruce tree prepared in Comparative Example 2, and the ethanol extract of the spruce tree prepared in Comparative Example 1, The combined extracts of P. aeruginosa, P. japonicus, P. japonicus, and P. japonica, which were prepared in Example 2, were assayed for tyrosinase activity.

Tyrosinase, an enzyme purified from potato or mushroom, was obtained from Sigma extracted from mushrooms. First, tyrosine, a substrate, was dissolved in a sodium phosphate buffer solution (0.1 M, pH 6.8) to prepare a solution having a concentration of 0.3 mg / ml. Then, 334 μl of the solution was taken into a test tube and then sodium phosphate buffer solution 0.1M, pH 6.8). The dried extracts of Comparative Examples 1 to 3 and Example 2 were dissolved in methanol to a concentration of 100 mg / ml, diluted with DMSO, and used as an experimental group. Each 2 μl of the diluted extract samples was added to the solution in the test tube and reacted in a 37 ° C thermostat for 10 minutes.

To evaluate tyrosinase activity of the sample, 1M Phosphate Buffer (PB) pH 6.8 was sterilized at 121 ° C for 20 minutes and cooled at room temperature (25 ° C). 1M Phosphate Buffer (PB) pH 6.8 was prepared at 1/15 M (final concentration = 66.6 mM) and L-DOPA was dissolved in phosphate buffer (pH 6.8) to a concentration of 2.0 mM. Tyrosinase was also dissolved in phosphate buffer (pH 6.8), and the concentration was adjusted to 46 units / ml.

In order to evaluate the tyrosinase activity, the sample compositions of the blank used in the experiment, the control, the single extract of Comparative Example 1, the combined extract of Comparative Examples 2 and 3, and the combined extract of Example 2 were as follows.

Blank (2 wells): 100 μl DMSO 2 μl, PB 160 μl, not treated

Control (2 wells): 2 μl of 100% DMSO, 120 μl of PB, 40 μl of Tyrosinase

Extract Sample: 2 ㎕ of sample, 120 ㎕ of PB, 40 ㎕ of tyrosinase

2 ㎕ of DMSO, 120 ㎕ of PB and 40 ㎕ of Tyrosinase were treated with 2 ㎕ of DMSO, 2 ㎕ of DMSO, 120 ㎕ of PB, and 120 ㎕ of PB, Tyrosinase And 40 μl of L-DOPA solution (2 mM) were added to each well. After incubation at 37 ° C for 10 min, OD (absorbance) was measured at 475 nm using a microplate counter. For arbutin used as a positive control, arbutin was dissolved in DMSO to a concentration of 100 mg / ml, and then diluted with DMSO to 100 μg / ml.

Tyrosinase activity was calculated using the following equation (1), and the results are shown in Table 2 and FIG.

Equation 1

Inhibition (%) = 1- (ControlO.D-SampleO.D) / (ControlO.D-BlankO.D) * 100 (%)

division Tyrosinase  The concentration of the sample inhibiting the activity by 50% (IC ₅₀  : [Mu] g / ml) Comparative Example 1 As a participant 12.25 Spruce tree > 40 Goblin debt > 40 Quince tree > 40 Comparative Example 2 Participation by: Phalaenopsis
(1: 1) 22.45 Comparative Example 3 Participation road: spruce tree: goblin debt
(1: 1: 1) 35.4 Example 2 Participation road: Spruce tree: Beetle Debt: Fruit tree
(2: 2: 1: 1) 15.7 Arbutin (positive control) 87

As shown in the above Table 2, compared with the single extract of Comparative Example 1, the compound extract of Comparative Example 2, and the compound extract of Comparative Example 3, the combined extract of Example 2, sprout, The IC ₅₀ The amount of tyrosinase was significantly lower than that of arbutin, and the ability to inhibit the activity of tyrosinase was 5 times higher than that of arbutin.

Fig. 2 is a graph showing the tyrosinase activity (%) of the complex extract of the present invention. As shown in FIG. 2, tyrosinase activity was significantly lower in the positive control group than in the arbutin at the concentrations of 100 μg / ml and 20 μg / ml in the extracts of P. japonica, P. sp. In particular, at a concentration of 20 μg / ml of the complex extract, tyrosinase activity was markedly lower than 100 μg / ml of arbutin, indicating that the efficiency of inhibiting tyrosinase activity was remarkably high.

On the other hand, in the case of the extract alone, the concentration of the sample inhibiting 50% inhibition of tyrosinase activity was 12.25 / / ml, unlike the extracts of spruce, 2 complex extracts. However, in the case of the extract alone, the DPPH radical scavenging ability was low as shown in Experimental Example 1, and thus it was impossible to apply the extract to antioxidant use. On the contrary, with the participation of the present invention, the combined extracts of spruce, decanter, and quercetin have not only antioxidative activity but also excellent whitening activity, so that they can be applied simultaneously for antioxidative and whitening purposes.

As a result of the present invention, the combined extracts of the spruce tree, the spruce tree, and the spruce tree were found to be the extracts of the spruce tree, the spruce tree, the extract of the spruce tree, the combined extract of the spruce tree and the spruce tree, Compared with the complex extract, the tyrosinase activity, which plays a key role in the melanin biosynthesis process, is suppressed to a remarkably high level, and the production of melanin pigment is effectively inhibited, thereby preventing skin aging and whitening effect. In addition, as described above, it has an excellent antioxidative effect.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.

Claims (3)

V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.
V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.
V eratrum There is nigrum . ussuriense ), spruce ( Juglans mandshurica , Rodgersia podophylla , and Chaenomeles Sinensis ) or a fraction thereof as an active ingredient.

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