KR102567997B1 - A Composition for anti-inflammatory or anti-oxidation comprising fermented placenta and its use - Google Patents

Abstract

The present invention relates to an anti-inflammatory or antioxidant composition. The composition according to the present invention reduces the excessive secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and prostaglandin E2 (PGE2), thereby exhibiting an anti-inflammatory effect, and the composition according to the present invention inhibits high ORAC activity and DPPH free radical activity, thereby exhibiting an antioxidant effect.

Description

Anti-inflammatory or antioxidant composition containing a fermented placenta composition as an active ingredient and its use

The present invention relates to anti-inflammatory and/or antioxidant compositions.

It is a widely known fact that inflammatory reactions and oxidative stress in the body cause various deterioration of body functions and diseases. Therefore, various studies have been conducted to improve it through anti-inflammatory and antioxidant substances capable of suppressing the inflammatory response and oxidative stress in the body.

Inflammation is an innate immune response caused by pathogen invasion or tissue damage, and is a complex process triggered by various immune cells. During the inflammatory process, immune cells such as macrophages perform phagocytosis in response to invasion by pathogens or secrete inflammatory factors such as cytokines to remove pathogens. If this inflammatory response is not controlled, damage to the body is induced. In fact, systemic inflammation such as sepsis caused by excessive inflammation caused by bacterial invasion shows a high mortality rate of 30 to 60%, and the cause of such high mortality is organ failure due to organ function loss due to inflammation. Therefore, since the inflammatory factors secreted in large amounts can lead to various diseases and death, countermeasures against excessive inflammation are necessary (Bae Ki-chun et al., Kor J Herbology 2012; 27 (6): 55-61).

Oxidative stress is caused by reactive oxygen species generated when oxygen used as an energy source in the body is incompletely reduced. It occurs even in normal conditions, but when it occurs excessively, it becomes a major factor in the occurrence of various diseases. In diabetes, oxidative stress interferes with glucose uptake in muscle and fat and reduces insulin secretion from pancreatic β-cells. In blood vessels, inflammation is induced by interaction with immune cells, resulting in disorders of vascular function. In addition, it is related to metabolic diseases, and it has been found that there are a large amount of phagocytic cells in obese adipose tissue, and since activated phagocytes actively generate oxidative stress, it is believed to play a role in increasing oxidative stress generation in obese adipose tissue. (Choi Young-eun et al., J Korean Acad Fam Med 2006; 27: 773~781).

Natural products have been used for various purposes in both the East and the West, and are excellent in terms of safety, short development period, and high probability of success, so their importance is highlighted, and the development of excellent natural products with anti-inflammatory and / or antioxidant effects something is being demanded

Republic of Korea Patent No. 10-0901138

The problem to be solved by the present invention is to provide a natural product that is safe to the human body with few side effects and has excellent anti-inflammatory and/or antioxidant effects, that is, such a useful use of a natural product.

In other words, the problem to be solved by the present invention is to provide a composition comprising a natural product having excellent anti-inflammatory and/or antioxidant effects as an active ingredient.

In order to solve the above problems, the present invention is a mammalian fermented placenta; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10) and any one selected from the group consisting of snail extract, or provides an anti-inflammatory and / or antioxidant composition comprising two or more of them as an active ingredient, preferably a cosmetic It provides a composition, pharmaceutical composition or health functional food composition.

As a result of research efforts to develop natural materials having anti-inflammatory or antioxidant effects, the inventors of the present invention have found that any one selected from the group consisting of fermented mammalian placenta, coenzyme Q10, fucoidan and snail extract, or two or more of them as active ingredients. The present invention was completed by confirming that the composition has anti-inflammatory and/or antioxidant effects. That is, the inventors of the present invention are mammalian fermented placentas; And a composition comprising any one selected from the group consisting of fucoidan, coenzyme Q10, and snail extract, or two or more of them as active ingredients, interleukin-1β (IL-1β), interleukin-6 (IL -6) and prostaglandin E2 (PGE2) were experimentally confirmed to reduce excessive secretion to show anti-inflammatory effects, and high ORAC activity and DPPH free radical activity inhibition were experimentally confirmed to show antioxidant effects.

As used herein, the term "anti-inflammation" refers to suppressing inflammation, and the inflammation is one of the defense responses of living tissues to certain stimuli, which causes tissue deterioration, circulatory disorder and exudation, and tissue proliferation. refers to complex lesions. More specifically, inflammation is part of innate immunity, and as in other animals, innate immunity in humans recognizes cell surface patterns that are specific to pathogens. Phagocytes recognize cells with such surfaces as non-self and attack the pathogen. If pathogens break through the body's physical barriers, an inflammatory response occurs. Inflammatory response is an immunological defense mechanism to recover and regenerate the damaged part when the body is damaged by various factors, but when it occurs excessively or continuously, acute or chronic inflammatory diseases are induced. This may later cause diseases such as circulatory disorders, multiple sclerosis, and Parkinson's disease. Inflammation occurs in various mechanisms in the body, such as hormone secretion, cytokines, and C-reactive protein (CRP), and there are many related substances. Among them, various cytokines secreted by immune cells regulate the immune system, and some promote inflammation. Therefore, the expression level of intracellular cytokines becomes an indicator of activation of the inflammatory response. In the present invention, the anti-inflammatory effect was confirmed through the suppression of inflammation-promoting cytokines and inflammatory cell active substances of the composition.

As used herein, the term "antioxidation" refers to inhibiting oxidative stress. Substances that cause oxidative stress may occur in the human body. When oxygen used as an energy source in the body is incompletely reduced, active oxygen is liberated into the cytoplasm. These reactive oxygen species can damage surrounding cells and further promote tissue damage due to inflammation. However, these reactive oxygen species are generated even in normal circumstances, but if there is no antioxidant defense mechanism in the body, we cannot live. Therefore, various types of antioxidant defense systems are built in our body to counter normal oxidative stress (Park Jong-yeol et al., BioWave 2004; 6 (13)). However, if oxidative stress exceeds normal levels, the body suffers serious damage, so countermeasures against oxidative stress are necessary. Antioxidants are natural or synthetic substances that function to prevent or inhibit oxidative stress. To evaluate the antioxidant power of these substances, oxygen radical absorbance capacity (ORAC), total polyphenol contents, total flavonoid contents, DPPH free radical scavenging ability, ferric reducing/antioxidant power (FRAP), etc., and these methods are mainly a measure of free radical removal ability such as active oxygen or antioxidant content. In the present invention, the antioxidant effect of the composition was confirmed through the free radical scavenging activity.

In the present invention, the placenta (placenta) refers to a structure that mediates the exchange of substances necessary for the survival and growth of the fetus between the fetus and the mother. In the present invention, the placenta may preferably be a mammalian placenta, for example, a placenta of a human, swine, horse, sheep, or cow may be used, but the human placenta is not used in industries other than pharmaceuticals. It is regulated and ethically questionable, so porcine placenta can be used more preferably.

The present inventors have confirmed better anti-inflammatory and/or antioxidant effects using fermented placenta than using mammalian natural placenta, and therefore fermented placenta can be preferably used. In the present invention, the fermented placenta refers to a placenta fermented with a fermenting microorganism, and is not limited thereto, but a commercially available placenta may be purchased and fermented, or a commercially available fermented placenta may be used. The method for fermenting the placenta may be used without limitation as long as it is a conventional method for fermenting the placenta in the art.

For example, a method for preparing a fermented placenta may include (S1) crushing a mammalian placenta and removing sweet blood; And (S2) may include the step of adding and fermenting the fermenting microorganism, and mixing by adding the carbon source and / or energy source of the fermenting microorganism added before or in the step (S2) of the step (S2). may include, and the carbon source and/or energy source may use any one known in the art. For example, oligosaccharides, lactose, glucose, fructose, sucrose, galactose, maltose, starch, or a mixture of two or more thereof may be used, and preferably monosaccharides or disaccharides may be used. In addition, it may be added in an arbitrary range in consideration of fermentation time, fermentation degree, and the like. For example, it may be added in the range of 3 to 30 parts by weight based on 100 parts by weight of the ground placenta.

In the step (S1), the size of the pulverized product of the mammalian placenta is not particularly limited to any size, but it is preferable that the pulverized product is uniformly fermented by the microorganisms to be added. The size refers to the longest length when the length is measured in the pulverized particles, and the size enough to be uniformly fermented by the added microorganisms can be determined within the range of ordinary ability in the art. For example, it may be used after being pulverized to a size of 0.3 to 1 mm. Mammalian placenta usually has about 90% water content, so it is not necessary to supply special water for fermentation. can ferment.

In the step (S2), the fermenting microorganisms may be microorganisms such as lactic acid bacteria, Bacillus genus or yeast, but are not limited thereto.

The fermenting microorganism is Aspergillus genus ( Aspergillus sp.), Penicillium sp., Rhizopus sp., Acetobacter sp., Saccharomyces sp., Torulopsis sp. .), all microorganisms capable of fermentation, such as lactic acid bacteria, may be used, and more preferably Saccharomyces sp. and lactic acid bacteria are appropriate. It may be added in an arbitrary range in consideration of fermentation time, fermentation degree, and the like. For example, it may be added in the range of 3 to 30 parts by weight based on 100 parts by weight of the ground placenta.

The lactic acid bacteria are Lactobacillus sp., Streptococcus sp., Pediococcus sp., Leuconostoc sp., and Bifidobacterium genus. Lactic acid bacteria ( Bifidobacterium sp.) and the like. More specifically, Lactobacillus plantarum , Lactobacillus delbueckii , Lactobacillus bulgaricus , Lactobacillus casei , Lactobacillus brevis, Lactobacillus brevis , Lactobacillus acidophilus, Pediococcus pentosaceus, Pediococcus cerevisiae ( Pediococcus ) cerevisiae ), Leuconostoc citreum ( Leuconostoc citreum ), Leuconostoc mesenteroides ( Leuconostoc mesenteroides ), Bifidobacterium bifidum ( Bifidobacterium bifidum ), Bacillus coagulans ( Bacillus coagulans ) and the like may be used.

In the case of yeast, Saccharomyces sp. yeast is preferred, and such yeast is, for example, Saccharomyces lucy ( Saccharomyces sp.) rouxii ), Saccharomyces cerevisiae ( Saccharomyces cereviciae ), Saccharomyces obiformis ( Saccharomyces oviformis ), Saccharomyces steineri ( Saccharomyces steineri ), Saccharomyces ellipsoidus ( Saccharomyces ellipsoideus ), Saccharomyces Koreanus ( Saccharomyces coreanus ) and the like may be used.

In the case of Bacillus sp., Bacillus subtilis ( Bacillus subtilis ), Bacillus lichneformis ( Bacillus lichneformis ), Bacillus megaterium ( Bacillus megaterium ), Bacillus amyloliquefaciens ( Bacillus amyloliquefaciens ), Bacillus Natto ( Bacillus natto ), Bacillus antarsis ( Bacillus antharcis ), Bacillus lentus ( Bacillus lentus ), Bacillus pumilus ( Bacillus pumilus ), Bacillus thuringiensis ( Bacillus thuringiensis ), Bacillus alvei ( Bacillus alvei ), Bacillus azo Topic Sans ( Bacillus azotofixans ), Bacillus Macerans , Bacillus polymyxa , Bacillus polilliae , Bacillus coagulans , Bacillus stearothermophilus , Bacillus pasteurii , Bacillus sphaericus , Bacillus fastidiosus , and the like may be used.

In addition, in the step (S2), it is preferable to ferment until the growth of the added microorganism reaches the maximum. The point at which the growth of the added microorganism reaches the maximum may be determined according to the fermentation temperature, the amount of the fermentation raw material, the amount of the added microorganism, and the like. A person skilled in the art can determine the point at which the growth of the added microorganism reaches the maximum by considering the fermentation temperature, the amount of the fermentation raw material, the amount of the inoculated microorganism, and the like within the range of his/her ordinary ability.

Fermentation in step (S2) may be performed within the range of 15 ° C to 45 ° C, preferably within the range of 20 ° C to 40 ° C. When the fermentation temperature is lower than the above range, the fermentation rate may be slowed and unwanted fermentation products may be produced, and when the fermentation temperature is higher than the above range, the fermentation rate may be slowed down or unwanted fermentation products may be produced due to the death of the fermentation microorganisms. can

In addition, a aging step may be additionally included after the step (S2). The aging step is for stabilizing the fermentation product by the microorganism even after the growth of the added microorganism is stopped, but is not limited thereto, and may be performed for 10 days to 12 months.

In addition, a sterilization step may be additionally included after the step (S2). The sterilization step may be performed using a conventional method known in the art, such as heat treatment and ultraviolet radiation.

The fermented placenta prepared according to the method for preparing the fermented placenta is initially obtained in liquid form, but may be concentrated by methods such as vacuum concentration or freeze drying or used in powder form, and precipitated with an appropriate precipitant such as ethanol or acetone to obtain a supernatant. After removal, the precipitate may be recovered and used.

The fucoidan is a sulfated polysaccharide having a sticky viscous structure, and is a substance in which a basic sugar called fucose and a sulfate group are bonded. In the present invention, fucoidan can be purchased commercially or purified from cultivation or collection in nature. For example, seaweed, kelp, mozuku, sugar kelp ( Laminaria saccharina ), L. digitata ( L. digitata ), Pacific hat half ( Fucus distichus ), Okinawa mozuku ( Cladosiphon) It may be isolated from brown algae such as okamuranus ), but is not limited thereto.

The composition according to the present invention may contain 0.1 to 5 parts by weight of the fucoidan, preferably 0.5 to 3 parts by weight, based on 100 parts by weight of the fermented placenta.

The coenzyme Q10 (coenzyme Q10) is one of the coenzymes that act in the body and is a vitamin-like action factor called ubiquinone, vitamin Q, and the like. In the present invention, coenzyme Q10 may be purchased commercially or derived from nature, but is not limited thereto.

The composition according to the present invention may include 0.1 to 5 parts by weight, preferably 0.5 to 3 parts by weight of the coenzyme Q10, based on 100 parts by weight of the fermented placenta.

Snails are carnivorous shellfish belonging to the gastropod or snail family (Fruticiola sieboldiana), and about 20,000 species are known worldwide. The main nutritional components of snails are known as protein, lipid, carbohydrate, and ash, and are especially rich in protein and calcium. The component constituting the sticky mucus secreted by snails is called mucin, and the main component constituting mucin is chondroitin sulfate.

All edible snails may be used as the snail. Preferably Helix Aspera , Helix Pomatia , Helix Lucorum , Helix Lactea , Helix Adanensis , Helix Kincta ), Helix hortensis ( Helix hortensis ), Teva Pisana ( Theba pisana ), Achatina Purica fulica ), Eotala vermiculata ( Otala vermiculata ), and Cantareus Apertus ( Cantareus apertus ) may be used, but are not limited thereto.

In the present invention, the snail extract may be purchased commercially or extracted from snails collected in nature. For example, the extract may refer to a product such as a liquid component obtained by immersing a desired substance in various solvents and then extracting at room temperature or a warm state for a certain period of time, and a solid component obtained by removing the solvent from the liquid component. there is. In addition, in addition to the above results, it can be comprehensively interpreted as including all dilutions of the results, concentrates thereof, adjusted products, and purified products thereof. The method for obtaining the extract is not particularly limited thereto as long as an extract having anti-inflammatory and/or antioxidant effects can be obtained, but, for example, the snail is immersed in a solvent and extracted at room temperature of 10 ° C to 25 ° C. Methods such as a cold needle extraction method, a heat extraction method in which extraction is performed by heating to 40 ° C. to 100 ° C., an ultrasonic extraction method in which ultrasonic extraction is applied, and a reflux extraction method using a reflux condenser may be used.

The composition according to the present invention may contain 0.1 to 5 parts by weight of the snail extract, preferably 0.5 to 3 parts by weight, based on 100 parts by weight of the fermented placenta.

Preferably, the composition is a mammalian fermented placenta; And fucoidan, coenzyme Q10, and snail extract may all be included as active ingredients. The present inventors experimentally confirmed that the anti-inflammatory and/or antioxidant effect of a composition containing all of fucoidan, coenzyme Q10, and snail extract as active ingredients on fermented placenta was excellent.

The composition according to the present invention is fermented placenta; And when all fucoidan, coenzyme Q10 and snail extract are included as active ingredients, the weight ratio of the fermented placenta, fucoidan, coenzyme Q10 and snail extract is 100: 0.1 to 5: 0.1 to 5: 0.1 to 5 (fermented placenta: fucoidan: Coenzyme Q10: snail extract), preferably 100: 0.5 to 3: 0.5 to 3: 0.5 to 3. If the contents of fucoidan, coenzyme Q10, and snail extract are lower than the above ratio, physiological activity may not be achieved as desired, and the functional level is insignificant compared to fermented placenta alone. In addition, if the ratio is higher than the above ratio, the quality of the composition may be adversely affected due to odor, moisture absorption or discoloration of the raw material itself.

In the cosmetic composition, pharmaceutical composition and health functional food composition according to the present invention, the content of the active ingredient is preferably 0.00001 to 100% by weight based on the total weight of the cosmetic composition, pharmaceutical composition and health food.

According to one embodiment of the present invention, the present invention is a mammalian fermented placenta; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10) and any one selected from the group consisting of snail extract, or two or more of them as an active ingredient It provides a cosmetic composition for anti-inflammatory and / or anti-oxidation.

Cosmetics prepared by containing the composition as an active ingredient as a cosmetic composition may be prepared in the form of general emulsified formulations and solubilized formulations. For example, lotion such as softening lotion or nourishing lotion, emulsion such as facial lotion, body lotion, etc., cream such as nourishing cream, moisture cream, eye cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, liquid It may have formulations such as foundation, powder, cleansing cream, cleansing lotion, makeup remover such as cleansing oil, cleanser such as cleansing foam, soap, body wash, etc., such as type, solid type or spray type, but is not limited thereto.

The composition may contain a relatively high concentration of the composition of the present invention in the case of wash-off type cosmetics, such as makeup removers and detergents, in which active ingredients stay on the skin for a short period of time when commercialized as cosmetics. will be. On the other hand, in the case of leave-on type cosmetics such as lotion, lotion, cream, essence, etc., in which active ingredients stay on the skin for a long time, the composition of the present invention is contained at a lower concentration than wash-off type cosmetics. It will be fine even if you do.

In addition, the cosmetic may include, in addition to the composition of the present invention, a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, Ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any commonly used in cosmetics It may contain adjuvants commonly used in the field of cosmetology, such as other ingredients of

In addition, the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers formulated in general skin cosmetics.

Cosmetically acceptable carriers included in the cosmetic composition of the present invention vary depending on the formulation. When the formulation of the present invention is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these may be used.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and especially in the case of a spray, chloro propellants such as fluorohydrocarbons, propane/butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3 -There is butyl glycol oil, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

When the dosage form of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, a micro Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier components. can

The present invention also provides a method for skin whitening, enhancing skin elasticity, improving skin wrinkles, or moisturizing the skin, comprising the step of applying the composition to the skin of a subject. The subject includes, without limitation, mammals including mice, livestock, humans, and the like.

In addition, according to one embodiment of the present invention, the present invention is a mammalian fermented placenta; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10) and any one selected from the group consisting of snail extract, or two or more of them as an active ingredient It provides a pharmaceutical composition for anti-inflammatory and / or antioxidant use.

The composition is a solution, gel, emulsion, suspension, micro-emulsion, micro-capsule, liposome, cream, lotion, ointment, aerosol ( aerosol), spray, paste, and patch.

The pharmaceutical composition of the present invention can be used as a single formulation, or can be prepared and used as a combination formulation by further including a drug known to have a recognized anti-inflammatory or antioxidant effect, formulated using a pharmaceutically acceptable carrier or excipient. By doing so, it can be prepared in unit dose form or prepared by inserting it into a multi-dose container.

As used herein, the term "pharmaceutically acceptable carrier" may refer to a carrier or diluent that does not inhibit the biological activity and properties of the injected compound without irritating living organisms. The type of the carrier that can be used in the present invention is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable can be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and the like. These may be used alone or in combination of two or more. The carrier may include a non-naturally occurring carrier.

In addition, if necessary, other conventional additives such as antioxidants, buffers, and/or bacteriostatic agents may be added and used, and diluents, dispersants, surfactants, binders, lubricants, etc. may be additionally added to form main solutions such as aqueous solutions, suspensions, and emulsions. It may be formulated into a dosage form, pill, capsule, granule or tablet for use.

In addition, the pharmaceutical composition of the present invention is a mammalian fermented placenta in a pharmaceutically effective amount; And it may include any one selected from the group consisting of fucoidan, coenzyme Q10, and snail extract, or two or more of them. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to induce an anti-inflammatory or antioxidant effect at a reasonable benefit / risk ratio applicable to medical treatment, generally in an amount of 0.001 to 1000 mg / kg, Preferably, an amount of 0.05 to 200 mg/kg, more preferably 0.1 to 100 mg/kg may be divided and administered once or several times a day. However, for purposes of the present invention, a specific therapeutically effective amount for a particular patient is determined by the type and extent of the response to be achieved, the specific composition, including whether other agents are used as the case may be, the patient's age, weight, general state of health, It is preferable to apply differently according to various factors including gender and diet, administration time, administration route and secretion rate of the composition, treatment period, drugs used together with or concurrently used with a specific composition, and similar factors well known in the medical field.

In another embodiment of the present invention, fermented mammalian placenta; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10) (coenzyme Q10), and any one selected from the group consisting of snail extract, or anti-inflammatory and / or antioxidant function comprising the step of administering to the subject a composition containing two or more of them as an active ingredient Provides a method of enhancement.

As used herein, the term "subject" includes, but is not limited to, all mammals, including mammals that require or may need anti-inflammatory or antioxidant functions, preferably humans. The mammal may be not only humans but also mammals such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, and cats that require enhancement of anti-inflammatory and/or antioxidant functions, but are not limited thereto.

Specifically, the anti-inflammatory and/or antioxidant function enhancing method of the present invention may include administering the composition to a subject in a pharmaceutically effective amount.

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a patient by any suitable method, and the route of administration of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. Orally, it can be administered through various routes.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without causing side effects in consideration of all of the above factors, and can be easily determined by a person skilled in the art.

The administration method of the pharmaceutical composition according to the present invention is not particularly limited, and may follow a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered by oral administration or parenteral administration. The pharmaceutical composition according to the present invention may be prepared in various formulations depending on the desired administration method.

The frequency of administration of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times by dividing the dose.

The present invention also relates to mammalian fermented placentas; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10), and provides a quasi-drug composition comprising any one selected from the group consisting of snail extract or two or more of them as an active ingredient.

As used herein, the term “quasi-drugs” refers to textiles, rubber products, or similar products used for the purpose of treating, alleviating, treating, or preventing diseases of humans or animals, devices that have weak effects on the human body or do not directly act on the human body, and devices or non-machines and similar items, products falling under one of the agents used for sterilization, insecticidal, and similar purposes to prevent infectious diseases, for the purpose of diagnosing, treating, mitigating, treating, or preventing human or animal diseases It may refer to items other than instruments, machines or devices among items used and items other than instruments, machines or devices among items used for the purpose of pharmacologically affecting the structure and function of humans or animals. In addition, the quasi-drugs may include external skin preparations and personal hygiene products. Preferably, it may be a disinfectant cleaner, shower foam, gargreen, wet tissue, detergent soap, hand wash, or ointment, but is not limited thereto.

When the composition according to the present invention is used as a quasi-drug additive, the composition may be added as it is or used together with other quasi-drugs or quasi-drug ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use.

In addition, according to one embodiment of the present invention, the present invention is a mammalian fermented placenta; And fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10), and any one selected from the group consisting of snail extract, or two or more of them as an active ingredient for anti-inflammatory and / or antioxidant health functional food composition It provides.

As used herein, the term "health functional food" refers to the fermented placenta of the mammal; And any one selected from the group consisting of fucoidan, coenzyme Q10, and snail extract, or two or more of them are added to food materials such as beverages, teas, spices, gum, confectionery, etc., or encapsulated or powdered. It is a food prepared as a suspension, etc., which means that it brings a specific effect on health when ingested, but unlike general drugs, it has the advantage of not having side effects that can occur when taking a drug for a long period of time using food as a raw material. Since the health food of the present invention obtained in this way can be consumed on a daily basis, excellent anti-inflammatory and/or antioxidant effects can be expected, and is very useful.

The health functional food composition of the present invention may further include a food-acceptable carrier.

The type of food to which the composition of the present invention can be added is not particularly limited, and for example, there are various beverages, chewing gum, tea, vitamin complexes, health supplements, and the like. Other ingredients that do not interfere with the anti-inflammatory or antioxidant effect may be added to the food composition, and the type is not particularly limited. For example, it may contain various herbal extracts, food-acceptable food additives, or natural carbohydrates as additional ingredients, like conventional foods.

The food additives may be appropriately selected and used by those skilled in the art as being added to prepare health functional foods of each formulation. For example, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators , stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. are included, but the types are not limited by the above examples.

In general, when preparing food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. . There is no particular limitation on the type of food. Examples of foods to which the substance can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages, vitamin complexes, etc., and includes all health functional foods in a conventional sense.

If the food is a beverage, it may be included in a ratio of 1 to 30 g, preferably 3 to 20 g, based on 100 ml. In addition, the composition may include additional ingredients that are commonly used in food compositions to improve odor, taste, and visual properties. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu) may be included. In addition, amino acids such as lysine, tryptophan, cysteine, and valine may be included. In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene ( BHT), etc.), coloring agents (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG (sodium glutamate), etc.), sweeteners (dulcin, cyclemate, saccharin, sodium Food additives (e.g.), flavorings (vanillin, lactones, etc.), expanding agents (alum, D-potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (thickeners), coating agents, gumicides, foam inhibitors, solvents, improvers, etc. food additives) may be added. The additive is selected according to the type of food and used in an appropriate amount. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

The health functional food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the preparation. In addition, unlike general medicines, there is an advantage in that there is no side effect that may occur when taking medicines for a long time by using food as a raw material, and it can be excellent in portability.

The composition according to the present invention reduces the excessive secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and prostaglandin E2 (PGE2), thereby exhibiting an anti-inflammatory effect, and the composition according to the present invention inhibits high ORAC activity and DPPH free radical activity, thereby exhibiting an antioxidant effect.

1 shows the anti-inflammatory effect by inhibiting excessive secretion of interleukin-1β (IL-1β) according to Examples and Comparative Examples of the present invention.
Figure 2 shows the anti-inflammatory effect by suppression of excessive secretion of interleukin-6 (IL-6) according to Examples and Comparative Examples of the present invention.
Figure 3 shows the anti-inflammatory effect by inhibiting excessive secretion of prostaglandin E2 (PGE2) according to Examples and Comparative Examples of the present invention.
Figure 4 shows the antioxidant effect by ORAC (Oxygen Radical Absorbance Capacity) activity according to Examples and Comparative Examples of the present invention.
Figure 5 shows the antioxidant effect by DPPH free radical scavenging activity according to Examples and Comparative Examples of the present invention.

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

manufacturing example 1: Preparation of composite composition ( comparative example 1 to 4; Example 1 to 5)

Non-fermented normal pig placenta and fermented pig placenta were purchased and used from Horus Co., Ltd., Japan, and were used as fucoidan powder. Q10 (Kaneka Nutrients Co, USA) and snail extract (Iris Trade, INC., USA) were commercially available, and a composite composition was prepared in the following ratio.

composition ratio common
money placenta fermentation
money placenta fucoidan
powder coenzyme
Q10 snail
extract Purified water total Comparative Example 1 - - 1.5 - - 102 103.5 Comparative Example 2 - - - One - 102.5 103.5 Remark example 3 - - - - One 102.5 103.5 Comparative Example 4 100 - - - - 3.5 103.5 Example 1 - 100 - - - 3.5 103.5 Example 2 - 100 1.5 - - 2 103.5 Example 3 - 100 - One - 2.5 103.5 Example 4 - 100 - - One 2.5 103.5 Example 5 - 100 1.5 One One - 103.5

Experimental example 1: Interleukin- by complex composition 1β (IL-1β) Excess secretion inhibitory effect

Cytokines are proteins secreted mainly by monocytes, lymphocytes, T cells, B cells, natural killer cells, and fibroblasts during an inflammatory response. Like neurotransmitters, they are receptors on cell membranes. Acts on cells or, like hormones, acts on intracellular receptors to transmit information between cells. Representative examples include interleukin (IL), interferon (IFN), chemokine, tumor necrosis factor (TNF), and transforming growth factor (TGF), among which promote inflammation (pro-inflammatory) cytokines include interleukin-1β, -2, -6 (IL-1β, -2, -6), IFN-γ, TNF-α, etc., and anti-inflammatory cytokines Examples include IL-4, IL-10, IL-11, IL-13, and TGF-β. Inflammation-promoting cytokines activate cyclo-oxygenase-2 (COX-2) to increase prostaglandine E2 (hereinafter referred to as PGE2) and activate inflammatory cells to induce an inflammatory process (Song Hu-lim et al., Journal of the Korean Society of Psychopharmacology 2013 24:5-10). In the present invention, the anti-inflammatory effect was evaluated through inhibition of the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), which are proteins that promote inflammation, but the types are not limited.

First, in order to measure interleukin-1β (IL-1β), mouse macrophage RAW 264.7 Mouse macrophage cell line (KCLB no 40071, Korean Cell Line Bank, Seoul, Korea) was purchased and 2.5×10 ⁶ cells/ml was used. At the cell concentration, 100 μl was dispensed into a 96-well microplate. The medium was DMEM (GibcoBRL, Grand Island, NY, USA) supplemented with 10% FBS (GibcoBRL, Grand Island, NY, USA) and 1% penicillin/streptomycin (Thermo Scientific Hyclone, Waltham, MA, USA). , 5% CO2, cultured in a 37 ℃ environment. The cell culture medium in which the RAW 264.7 cells were dispensed was treated with 1 μg/ml of Lipopolysaccharide (LPS) (Sigma, St. Louis, MO, US) to induce inflammation, and 10 μg of the sample prepared according to Preparation Example 1 was added to the culture medium. /ml concentration. Thereafter, the cells were cultured for 24 hours, and after centrifugation at 900 rpm and 4° C. for 5 minutes, the cell culture medium was recovered to confirm interleukin-1β (IL-1β) produced in the culture medium. Interleukin-1β (IL-1β) was measured using a commercially available IL-1β ELISA kit (Thermo Scientific Co., Waltham, MA, USA) according to the manufacturer's instructions.

As a result, as shown in FIG. 1, interleukin-1β (IL-1β) was found to be significantly increased in macrophages inflamed with LPS than in non-inflamed cells, but decreased again in cells treated with the sample. did The amount of cytokine secretion promoting inflammation was more reduced in cells treated with fermented pig placenta (Example 1) than in normal pig placenta (Comparative Example 4), and compared to single compositions (Comparative Examples 1 to 4, Example 1), the complex composition (Example 2 to 5) the amount of secretion decreased in the treated cells. In particular, it was confirmed that the cells treated with the composite composition (Example 5) containing all of the fermented pig placenta, fucoidan, coenzyme Q10, and snail extract recovered to a normal level.

Experimental example 2: Inhibitory effect of excessive secretion of interleukin-6 (IL-6) by the complex composition

First, the secretion amount of interleukin-6 (IL-6) in the cell culture medium obtained by treating the same sample as in Preparation Example 1 in the same manner as in Experimental Example 1 was confirmed. Interleukin-6 (IL-6) was measured using a commercially available IL-6 ELISA kit (Thermo Scientific Co., Waltham, MA, USA) according to the manufacturer's instructions.

As a result, as shown in FIG. 2, interleukin-6 (IL-6) was found to be significantly increased in macrophages inflamed with LPS than in non-inflamed cells, but decreased again in cells treated with the sample. did The amount of cytokine secretion promoting inflammation was more reduced in cells treated with fermented pig placenta (Example 1) than in normal pig placenta (Comparative Example 4), and compared to single compositions (Comparative Examples 1 to 4, Example 1), the complex composition (Example 2 to 5) The amount of secretion was decreased in the treated cells. In particular, it was confirmed that the cells treated with the complex composition (Example 5) containing all of fermented pig placenta, fucoidan, coenzyme Q10, and snail extract recovered to normal levels.

Experimental example 3: by composite composition Prostaglandin E2 (PGE2) Excess secretion inhibitory effect

First, the secretion amount of prostaglandin E2 (PGE2) in the cell culture medium obtained by treating the same sample as in Preparation Example 1 in the same manner as in Experimental Example 1 was confirmed. Prostaglandin E2 (PGE2) was measured using a commercially available PGE2 ELISA kit (MyBioSource Co., Ltd., San Diego, CA, USA) according to the manufacturer's instructions.

As a result, as shown in FIG. 3, prostaglandin E2 (PGE2) was found to be significantly increased in macrophages inflamed with LPS than in non-inflamed cells, but decreased again in the cells treated with the sample. The amount of cytokine secretion promoting inflammation was more reduced in cells treated with fermented pig placenta (Example 1) than in normal pig placenta (Comparative Example 4), and compared to single compositions (Comparative Examples 1 to 4, Example 1), the complex composition (Example 2 to 5) The amount of secretion was decreased in the treated cells. In particular, it was confirmed that the cells treated with the composite composition (Example 5) containing all of fermented pig placenta, fucoidan, coenzyme Q10, and snail extract recovered to normal levels.

As can be seen from the results of Experimental Examples 1 to 3, interleukin-1β (IL-1β), interleukin-6 (IL-1β) and interleukin-6 (IL-1β) in which the composite composition containing fermented pig placenta promotes inflammation in macrophages where inflammation is induced. 6), effective anti-inflammatory effect was confirmed by inhibiting the secretion of prostaglandin E2 (PGE2).

Experimental example 4: by composite composition ORAC (Oxygen Radical Absorbance Capacity) active

ORAC activity was evaluated by ROO (peroxyl radical) generated by the decomposition of AAPH (2,2'-azobis-2-methyl-propanimidamide, dihydrochloride). This oxidizes a fluorescent substance (fluorescein, 3',6'-dihydroxy-spiro[isobenzofuran-1[3H],9'[9H]-xanthen]-3-one) to a non-fluorescent substance, and the added antioxidant ability It is a method proposed by the US Department of Agriculture and the National Institute on Aging in 1996 as a method of measuring the degree of decrease in fluorescence by a sample with The higher the ORAC activity level, the higher the antioxidant capacity.

ORAC activity was measured using a commercially available ORAC assay kit (Cell Biolabs, Inc., San Diego, CA, USA) according to the manufacturer's instructions. As a standard, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) was used.

As a result, as shown in FIG. 4, the ORAC activity increased 5 times in the fermented pig placenta (Example 1) sample than in the normal pig placenta (Comparative Example 4), and a single composition (Comparative Examples 1 to 4, Example 1) Compared to the composite composition (Examples 2 to 5) increased in the sample. In particular, it was confirmed that the activity greatly increased in the sample of the composite composition (Example 5) containing all of the fermented pig placenta, fucoidan, coenzyme Q10, and snail extract.

Experimental example 5: by composite composition DPPH free radical scavenging activity

DPPH (2,2-Diphenyl-1-picrylhydrazyl) is a purple stable free radical that reacts with antioxidants to receive hydrogen and be reduced to decolorize. By comparing the DPPH free radical scavenging activity of samples using the same principle, their antioxidant ability can be evaluated. It can be interpreted that the higher the free radical scavenging activity (%), the higher the antioxidant capacity of the sample.

For DPPH (1,1-Diphenyl-2-picryl-hydrazyl) free radical scavenging activity, first, 4 mg of DPPH was dissolved in 100 ml of methanol to make a DPPH solution, and the composition of Preparation Example 1 was diluted in ethanol at a concentration of 100 μg/ml. 1 ml of ethanol containing the composite composition and 1 ml of DPPH solution were mixed well, and then allowed to stand at 37° C. for 30 minutes, and then absorbance was measured at 516 nm. Ethanol was used as a control.

The antioxidant capacity by the DPPH free radical scavenging activity method was obtained by Equation 1 below.

[Equation 1]

DPPH free radical scavenging activity = 100 - (absorbance of sample/absorbance of control) × 100

As a result, as shown in FIG. 5, the ORAC activity increased 5 times in the fermented pig placenta (Example 1) sample than in the normal pig placenta (Comparative Example 4), and a single composition (Comparative Examples 1 to 4, Example 1) Compared to the composite composition (Examples 2 to 5) increased in the sample. In particular, it was confirmed that the activity greatly increased in the sample of the composite composition (Example 5) containing all of the fermented pig placenta, fucoidan, coenzyme Q10, and snail extract.

As can be seen from the results of Experimental Examples 4 to 5, it was confirmed that the composite composition containing the fermented pig placenta exhibited highly inflammatory ORAC activity and DPPH free radical scavenging activity, and thus could be used as an effective antioxidant functional material.

Claims (8)

mammalian fermented placenta; and
Fucoidan (fucoidan), coenzyme Q10 (coenzyme Q10) and any one selected from the group consisting of snail extract, or an anti-inflammatory or antioxidant composition containing two or more of them as an active ingredient. According to claim 1,
The composition is a mammalian fermented placenta; and
An anti-inflammatory or antioxidant composition comprising fucoidan, coenzyme Q10 and snail extract as active ingredients. According to claim 2,
The weight ratio of the fermented placenta, fucoidan, coenzyme Q10 and snail extract is 100: 0.1 to 5: 0.1 to 5: 0.1 to 5 (fermented placenta: fucoidan: coenzyme Q10: snail extract), characterized in that anti-inflammatory or antioxidant composition . According to claim 1,
The fucoidan is an anti-inflammatory or antioxidant composition, characterized in that contained 0.1 to 5 parts by weight relative to 100 parts by weight of the fermented placenta. According to claim 1,
The coenzyme Q10 is an anti-inflammatory or antioxidant composition, characterized in that contained in 0.1 to 5 parts by weight relative to 100 parts by weight of the fermented placenta. According to claim 1,
The snail extract is an anti-inflammatory or antioxidant composition, characterized in that contained in 0.1 to 5 parts by weight relative to 100 parts by weight of fermented placenta. According to claim 1,
The mammal is an anti-inflammatory or antioxidant composition, characterized in that the pig. According to any one of claims 1 to 7,
The composition is anti-inflammatory or antioxidant composition, characterized in that used as a health functional food composition.