KR20220045274A - Composition for preventing or treating cell senescence associated diseases comprising Silybum marianum flower extract - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating, and treating cellular senescence-related diseases, containing a Silybum marianum flower extract. The composition of the present invention, through selective removal and restoration to young cells, can prevent, alleviate or treat skin damage, obesity and diabetes, neurodegenerative diseases, osteoarthritis, atherosclerosis, geriatric eye diseases, tissue fibrosis diseases, and skin aging according to the accumulation of senescent cells, so that it is possible to be usefully used as a cosmetic and pharmaceutical composition for the same.

Description

Composition for preventing or treating cell aging-related diseases comprising milk thistle flower extract {Composition for preventing or treating cell senescence associated diseases comprising Silybum marianum flower extract}

The present invention relates to a composition for preventing, treating, or ameliorating cellular aging-related diseases containing milk thistle flower extract as an active ingredient. It relates to a composition for effectively preventing, treating, or improving a disease or disorder caused by cellular aging by means of a milk thistle flower extract exhibiting a senomorphic effect to restore cell function and morphology.

About 45% of the elderly over the age of 85 experience a weakened state in which they cannot properly respond to physical dysfunction and stress, which is due to the accumulation of senescent cells in the tissues and organs of the individual. Accumulation of senescent cells not only decreases physical function, but also weakens the functions of surrounding tissues and organs, acting as the etiology of various age-related diseases such as cancer, degenerative brain disease, osteoarthritis, senile eye disease, diabetes, cardiovascular disease, and skin aging. . In particular, the senescence-associated secretory phenotype (SASP) secreted by senescent cells includes proteolytic enzymes such as cytokines and chemokines and proteolytic enzymes such as MMPs (Matrix Metalloproteinase). Contributes to the pathogenesis and progression of this disease (Nat Rev Mol Cell Biol 15(7), 482-496).

Therefore, studies that can delay or overcome aging are being conducted targeting senescent cells, and these studies are called senotherapeutics. Seno Therapeutics is divided into senolytics, which selectively removes only senescent cells, and senomorphics, which restores the function or shape of senescent cells like young cells. is being reported Senolytics exhibits selective apoptosis efficacy on senescent cells, and acts through BCR-ABL, Bcl, p53, HSP90 inhibitory pathways, etc. Substances showing efficacy include dasatinib and quercetin , ABT263, ABT737, FOXO4-DRI, 17-DMAG, etc. have been reported. These senolytics target substances are generally developed through a fibroblast replicative aging model that has a direct correlation with the maximum lifespan of an individual (Physiol Rev 73(3), 617-38; Exp Gerontol 37(10-11), 1165-74). When senolytics, which showed an effect in the actual replicative aging fibroblast model, were applied to the individual, results of improving aging diseases were reported. When a senolytic agent that showed efficacy in human fibroblasts was administered to aged mice, results of improving osteoarthritis, atherosclerosis, heart load, and pulmonary elasticity reduction were reported (International Patent Publication No. WO 2015/0116740), When the CD9 antibody showing senolytic efficacy in human fibroblasts and vascular endothelial cells was administered to LDLR or ApoE-deficient mice, results of improving atherosclerosis have also been reported (Korean Patent Publication No. 10-2016-0017603). In addition, when ganciclovir, which showed efficacy in mouse embryonic fibroblasts, was administered to aged mice, inflammation, bone marrow suppression and cardiac dysfunction were improved, and when Dasatinib and Quercetin complex were administered to aged mice It has been reported that daily hematopoietic stem cell function recovery, cardiovascular function and osteoporosis improvement, and exercise ability are improved. These research results provide evidence that cellular aging is the actual cause of individual aging, and that aging of individuals can be delayed or overcome through improvement of cellular aging. When senescent cells expressing p16 were selectively killed in mice, the results of improving age-related diseases such as lipodystrophy, glomerrulosclerosis, heart hypertropy, and cataract were more direct. is supported by To date, studies on substances that selectively kill senescent cells have focused on anticancer drugs and single compounds, and few studies have been done on natural products (Cancer Discov 7(2),165-176; Aging Cell 14). (4), 644-58).

On the other hand, milk thistle (milk thistle) is a perennial plant of the genus Asteraceae of the genus Asteraceae, an annual or biennial plant, and the leaves have clear white stripes. The genus name 'Silybum' comes from the Greek name Dioscorides gave to a plant similar to a certain thistle, and it is well known as milk thistle because a milky sap comes out when the leaf breaks. Bioactivity studies using milk thistle have been mainly conducted using silymarin, a component extracted from milk thistle seeds. In particular, it is known to exhibit great efficacy in hepatocytes. The antioxidant effect of silymarin on the liver is about 10 times that of vitamin E, and it prevents liver damage by removing free radicals by increasing the concentration of superoxide dismutase and glutathione, which are antioxidants in the body. and strengthen liver function. Korean Patent Application Laid-Open No. 10-2016-0140417 discloses that when milk thistle extract, post-fermented tea extract, and chitooligosaccharide are used together, there is an effect of improving liver function. In addition, silymarin acts to control blood sugar, so it shows good efficacy in improving diabetes. The hypoglycemic action of silymarin is due to its strong antioxidant action. In this regard, US Patent Publication No. 2011-0045066 discloses that silymarin increases the level of glutathione in the blood and reduces the elevated blood sugar by preventing the rise of free radicals in pancreatic beta cells.

As such, studies on physiological activity using milk thistle have been mainly conducted on silymarin extracted from milk thistle seeds. There is no known disease prevention and treatment effect (Exp Toxicol Pathol 63(6), 569-74; World J Hepatol 6(3), 144-149).

Milk thistle flowers from which seeds have been removed have been thrown away as by-products of crops. If these physiological activities can be studied and used as active ingredients according to physiological activities, it is expected that high added value can be given through recycling of waste resources.

As the rapid increase in the proportion of the elderly population, centered on developed countries such as Japan, Europe, and Korea, is emerging as a social problem as well as health and medical aspects, the development of materials that can improve aging and aging-related diseases is urgently needed.

Accordingly, the present inventors have been researching natural materials that can effectively remove senescent cells or restore the function and shape of senescent cells with little stimulation to fundamentally solve cell aging-related diseases. The present invention was completed by confirming that milk thistle flower extract induces apoptosis of senescent cells, reduces aging-related factors due to cellular aging, and has excellent human safety due to no skin irritation.

One object of the present invention is to selectively kill senescent cells or restore the function and shape of senescent cells using a composition comprising a milk thistle flower extract to prevent, improve or treat cellular aging-related diseases or disorders is to provide

Another object of the present invention is to provide a cosmetic composition for preventing or improving cellular aging-related diseases or disorders, comprising a milk thistle flower extract.

Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cell aging-related diseases or disorders comprising a milk thistle flower extract.

Another object of the present invention is to provide a food composition for preventing or improving cellular aging-related diseases or disorders, comprising a milk thistle flower extract.

The present invention relates to a composition for preventing, improving, and treating cell aging-related diseases or disorders, comprising a milk thistle flower extract as an active ingredient. More particularly, it relates to a senolytics and senomorphix composition containing a milk thistle flower extract as an active ingredient, and to a pharmaceutical composition, a cosmetic composition, and a food composition comprising the milk thistle flower extract as an active ingredient. , The composition has excellent human safety without skin irritation and cytotoxicity, while selectively killing senescent cells and restoring the function or shape of senescent cells like young cells. In addition, in the present invention, the composition comprising milk thistle flower extract as an active ingredient may be provided as a composition for improving aging or extending life. (Life-extending composition is an ambiguous term

In one aspect, the present invention provides a composition for preventing, treating, or improving cell aging-related diseases or disorders, comprising a milk thistle flower extract as an active ingredient.

Milk thistle (milk thistle) of the present invention is a perennial plant belonging to the genus Asteraceae White-patterned genus, Silybum marianum ( Silybum marianum ) and Silybum eburneum ( Silybum eburneum ). Silybum marianum means blessed milk thistle, and it is found throughout Europe, Asia, North Africa, China, Australia, etc., and Silybum eburneum is a silver milk seed. Commonly called silver milk thistle or elephant thistle, it is native to Algeria, Morocco, and Spain. All parts of milk thistle are edible, and leaves, stems, roots, and seeds are mainly used.

In the present invention, the term "extract" refers to a liquid component obtained by immersing a material including a target plant in various solvents, and then extracting and fractionating it for a certain period of time at room temperature or a warm state, and a solvent from the liquid component. It means a result such as solid content obtained by removing it. In addition, in addition to the result, it can be comprehensively interpreted as including all of the dilutions of the results, their concentrates, their preparations, and their purified products.

In the present invention, the “milk thistle flower extract” is extracted from milk thistle flowers, preferably from flowers from which milk thistle seeds have been removed.

The milk thistle flower extract of the present invention may be extracted using a conventional solvent known in the art, and the extracted liquid may be used in liquid form or may be used after concentration and/or drying. In this case, as the solvent, water, an anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), a mixed solvent of the lower alcohol and water, acetone, ethyl acetate, chloroform, or 1,3- Any one solvent of butylene glycol may be used. Preferably, extraction may be performed using methanol, ethanol or butanol. However, it is not particularly limited thereto, and since the degree of extraction and loss of the active ingredient of the extract may be different depending on the organic solvent to be extracted, it is preferable to select and use an appropriate organic solvent.

The extraction method is not particularly limited thereto, but includes cold extraction extraction, ultrasonic extraction, or reflux cooling extraction method, and it is preferably carried out by the ultrasonic extraction method.

In addition, the milk thistle flower extract can be obtained through a conventional purification process in addition to the extraction method using the extraction solvent. For example, separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. Through various purification methods additionally performed Milk thistle flower extract can also be obtained through the obtained fraction.

According to one specific embodiment of the present invention, after grinding the milk thistle flower in the shade, 0.5 to 20 times the weight of the dried sample, preferably 1 to 15 times the amount of C1 to water, ethanol, methanol, etc. An extraction method such as stirring extraction, hot water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction for about 20 to 70 hours, preferably 40 to 50 hours at room temperature using a C4 lower alcohol or a mixed solvent of water and ethanol Preferably, the extract obtained after ultrasonic extraction is filtered, concentrated under reduced pressure, or dried to obtain a milk thistle flower extract.

The milk thistle flower extract of the present invention may be all extracts, fractions, purified products, dilutions, concentrates, or dried products obtained in each step of extraction, fractionation, or purification.

The composition for preventing or treating cell aging-related diseases comprising the milk thistle flower extract of the present invention as an active ingredient contains 0.0001 to 20.0% by weight of the milk thistle flower extract, preferably 0.001 to 10.0, based on the total weight of the composition. % by weight. When the content of the milk thistle flower extract is less than 0.0001% by weight, the effect of removing senescent cells cannot be expected. Difficulties arise in preparing the formulation.

In the present invention, the cells include all cells that are present in the subject (in vivo) or cultured outside the subject (in vitro). The cells can be variously classified according to the shape and location of the cells, for example, skin cells (epidermal, dermal, dermal papilla, melanin, etc.), fibroblasts, adipocytes, stem cells, vascular cells, etc. .

In the present invention, the senescent cells refer to cells that are in a state in which they can no longer divide because the generation period is old or cell division is stopped in the case of cells existing in vivo. In the case of cells existing in vitro), it refers to cells in a state in which their function is stopped by drug treatment or subculture.

In the present invention, the “cell aging-related disease or disorder” refers to a disease or disorder caused by cellular aging, and refers to a disease or disorder caused by a decrease in cell function or a change in the morphology of cells due to cellular aging.

These senescence-related diseases or disorders may vary depending on the aged cells, but examples thereof include neurodegenerative diseases or disorders; cardiovascular disease or disorder; metabolic disease or disorder; lung disease or disorder; inflammatory or autoimmune diseases or disorders; transplant related disease or disorder; eye disease or disorder; proliferative disease or disorder; chemotherapy and radiotherapy side effects; geriatric diseases or disorders; fibrotic disease or disorder; skin disease or disorder; Or there is a disease or disorder according to the aging of stem cells.

As a specific example, when the cell aging is the aging of fibroblasts, chronic skin damage (dryness, eczema, wrinkles, birthmarks, scars, keloids, etc.), skin atrophy, obesity. Diabetes mellitus, neurodegenerative disease, osteoarthritis, osteoporosis, atherosclerosis, geriatric eye disease (eg, cataract, glaucoma, presbyopia, macular degeneration, etc.) or fibrosis (pulmonary fibrosis, cystic fibrosis, renal fibrosis, liver fibrosis, oral submucosal fibrosis, heart fibrosis, pancreatic fibrosis, etc.).

Examples of the neurodegenerative disease or disorder include cognitive impairment, Alzheimer's disease/dementia, Parkinson's disease, motor neuron dysfunction, Huntington's disease, and the like.

Examples of the cardiovascular disease or disorder include atherosclerosis, diastolic dysfunction, aortic aneurysm, cerebral aneurysm, angina pectoris, arrhythmia, cardiomyopathy, congestive heart failure, coronary artery disease, myocardial infarction, endocarditis, hypertension, carotid artery disease, peripheral arterial disease , heart load resistance, cardiac fibrosis, heart attack (coronary thrombosis), dyslipidemia (hypertriglyceridemia/hyperlipidemia, cholesterolemia), mitral valve prolapse, stroke, and cerebrovascular disease.

Examples of the metabolic disease or disorder include diabetes, dyslipidemia, obesity, metabolic syndrome, diabetic ulcer, insulin resistance, hepatic steatosis (steatohepatitis), and the like.

Examples of the lung disease or disorder include chronic obstructive pulmonary disease, pulmonary fibrosis, idiopathic pulmonary fibrosis, emphysema, bronchiolitis obliterans, asthma, cystic fibrosis, bronchiectasis, and the like.

Examples of the inflammatory or autoimmune disease or disorder include osteoarthritis and degenerative joint disease, rheumatoid arthritis, inflammatory bowel disease, mucositis (oral mucositis), and the like.

Examples of the eye disease or disorder include macular degeneration, cataract, glaucoma, visual impairment, presbyopia, and the like.

Examples of the proliferative disease or disorder include various cancers and metastasis of cancer, benign prostatic hyperplasia, and the like.

Examples of the side effects of chemotherapy and radiation therapy include fatigue / malaise / low physical activity, gastrointestinal toxicity, peripheral neuropathy, hematological toxicity, hepatotoxicity, cardiotoxicity, hair loss, pain, mucositis, fluid retention, dermatological toxicity, etc. .

Examples of the geriatric disease or disorder include osteoporosis, kyphosis, tremor, intervertebral disc herniation, liver disorder, renal dysfunction (renal failure, glomerulosclerosis, glomerulonephritis), weakness, urinary incontinence, gait disorder, alopecia, hearing loss, muscle fatigue, skin conditions, skin nevus, sarcopenia, skin wound healing, and other geriatric diseases induced by aging (eg, diseases/disorders resulting from smoking, high-fat/sugar diet, and environmental factors), and the like.

Examples of the fibrotic disease or disorder include pulmonary fibrosis, cystic fibrosis, renal fibrosis, liver fibrosis, oral submucosal fibrosis, cardiac fibrosis and pancreatic fibrosis, and the like.

Examples of the above skin diseases or disorders include psoriasis, eczema, wrinkles, loss of elasticity, pruritus, sensory disturbance, papular dystonia, erythroderma, lichen planus, lichenoid dermatosis, nevus, rash, urticaria, atopic dermatitis, eosinophilic dermatosis, Reactive neutrophil dermatosis, pemphigus, pemphigus, immune bullous dermatosis, dermal fibrous histiocytosis, dermal lymphoma, cutaneous lupus, hyperpigmentation, scar, keloid, strawberry nose, vitiligo, ichthyosis, dermatomyositis, age spots, blemishes, freckles, Melasma, actinic keratosis, etc.

In one specific implementation, it was confirmed that the milk thistle flower extract according to the present invention had excellent senolytic effects. Specifically, the milk thistle flower extract of the present invention reduces the cell viability of senescent cells but does not reduce the cell viability of young cells (see FIG. 1A ), and the milk of the present invention in co-cultured senescent cells and young cells. It was confirmed that the thistle flower extract had the effect of decreasing the proportion of senescent cells but increasing the proportion of young cells (see Fig. 1b). In addition, the milk thistle flower extract of the present invention was tested for senescent cells through apoptosis induction experiment. Although the expression rate and apoptosis of the apoptosis-related protein increased, the expression rate and apoptosis of the apoptosis-related protein of young cells did not increase (see FIGS. 2 and 3).

In another specific implementation, it was confirmed that the milk thistle flower extract according to the present invention had excellent senomolytic effects. Specifically, the milk thistle flower extract of the present invention reduced the increased SA-β-gal activity in senescent cells (see FIG. 4), and MMP-1, p-H2AX, p21, known as senescence-related indicators in senescent cells, The production of IL-6 and TNF-α was significantly reduced (see FIGS. 5 and 6).

Accordingly, the composition comprising the extract of milk thistle flower of the present invention has an effect of preventing, treating, or improving cellular aging-related diseases or disorders caused by senolytics and cenomoritox on senescent cells.

The senolytics means selectively exhibiting apoptosis efficacy on senescent cells, and the senomoritox means restoring the function or shape of senescent cells to normal cells.

In the present invention, the term "prevention" or "improvement" refers to changes in the function and structure of tissues and/or organs due to the accumulation of aged cells in an individual by administration of the composition according to the present invention, increased aging-related factors, etc. It means any action that inhibits or delays the onset of senescent cell-related diseases or disorders caused by, and "treatment" refers to the function of tissues and/or organs due to the accumulation of senescent cells by administration of the composition according to the present invention and Structural changes, increased senescence-related factors, etc. Suspected senescent cell-related diseases or disorders, and all actions that improve or beneficially change the symptoms of the affected individual.

In the present invention, the term "administration" means introducing the composition of the present invention to an individual by any suitable method, and the administration route of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. It can be administered through

The administration method of the 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. Preferably, parenteral administration, more preferably, it may be applied in the form of topical application by application or invasiveness.

In the present invention, the term "individual" refers to the onset or possibility of senescent cell-related diseases or disorders caused by changes in the function and structure of tissues and/or organs due to the accumulation of senescent cells, increased senescence-related factors, etc. It can mean any animal, including humans. The animal may be a mammal, such as a cow, a horse, a sheep, a pig, a goat, a camel, an antelope, a dog, or a cat, in need of treatment for symptoms similar to those of a human as well as humans, but is not limited thereto.

On the other hand, the milk thistle flower extract of the present invention is a natural material, harmless to the human body, and has almost no toxicity and side effects, so it can be safely used even for long-term use, so it can be safely applied to pharmaceutical, cosmetic and food compositions containing it. .

In one specific embodiment, the composition comprising the extract of milk thistle flower of the present invention is provided as a pharmaceutical composition for preventing or treating cellular aging-related diseases or disorders.

The milk thistle flower extract of the present invention and its preventive or therapeutic effect on cellular aging-related diseases or disorders are as described above.

The pharmaceutical composition of the present invention may further include a carrier generally acceptable to the pharmaceutical composition in addition to the milk thistle flower extract as an active ingredient.

Carriers commonly acceptable for the pharmaceutical composition are those commonly used in the formulation, and include carbohydrate compounds (eg, lactose, amylose, dextrose, sucrose, sorbitol, mannitol, starch, cellulose, etc.), acacia gum, phosphoric acid. Calcium, Alginate, Gelatin, Calcium Silicate, Microcrystalline Cellulose, Polyvinylpyrrolidone, Cellulose, Water, Syrup, Salt Solution, Alcohol, Gum Arabic, Vegetable Oil (e.g. Corn Oil, Cottonseed Oil, Soy Milk, Olive Oil, coconut oil), polyethylene glycol, methyl cellulose, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, and mineral oil.

The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components. Suitable pharmaceutically acceptable carriers and agents are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be applied to mammals such as rats, mice, livestock, and humans by oral or parenteral administration, preferably parenteral administration, more preferably topical administration by application or invasive application) can be applied.

A suitable dosage of the pharmaceutical composition may be variously prescribed depending on factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient. there is. The oral dosage of the pharmaceutical composition of the present invention is within the range of 0.001-300 mg/kg (body weight) for adults. In addition, in the case of an external preparation, it is recommended to apply it once to 5 times a day in an amount of 1.0 to 3.0 ml based on an adult and continue it for at least 1 month. However, the dosage does not limit the scope of the present invention.

In another specific embodiment, the composition comprising the extract of milk thistle flower of the present invention is provided as a cosmetic composition for preventing or improving cell aging-related diseases or disorders.

More specifically, the composition comprising the extract of milk thistle flower of the present invention is provided as a cosmetic composition for preventing or improving cell aging-related skin diseases or disorders.

The effect of preventing or improving the milk thistle flower extract of the present invention and its cellular aging-related diseases or disorders is as described above.

The cosmetic composition of the present invention is particularly suitable for the prevention or improvement of cellular aging-related skin diseases or disorders. The cellular aging-related skin disease or disorder is not necessarily limited thereto, but psoriasis, eczema, wrinkles, loss of elasticity, pruritus, sensory disturbance, papular tongue disorder, erythrodermatosis, lichen planus, lichen planus, nevus, rash, urticaria , atopic dermatitis, eosinophil dermatosis, reactive neutrophil dermatosis, pemphigus, pemphigoid, immune bullous dermatosis, dermal fibrous histiocytosis, dermal lymphoma, dermal lupus, hyperpigmentation, scar, keloid, strawberry nose, vitiligo, ichthyosis, skin Any one or more may be selected from the group consisting of myositis, age spots, blemishes, freckles, melasma, and actinic keratosis.

The cosmetic composition may additionally include ingredients commonly used in the cosmetic composition in addition to the milk thistle flower extract. For example, it may contain conventional adjuvants and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances.

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

When the formulation of the cosmetic composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. can be used

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

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

When the formulation of the cosmetic composition is a suspension, as a carrier component, 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; Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.

When the formulation of the cosmetic composition is surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid as carrier components Amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters can be used.

The cosmetic composition comprising the milk thistle flower extract of the present invention as an active ingredient contains 0.0001 to 20.0 wt%, preferably 0.001 to 10.0 wt%, of the milk thistle flower extract based on the total weight of the composition. When the content of the milk thistle flower extract is less than 0.0001% by weight, the effect of removing senescent cells and restoring the function or shape of senescent cells like young cells to prevent and improve cellular senescence-related diseases cannot be expected, and 20.0% by weight If it is exceeded, the amount of increase in the effect according to the increase in the content is insignificant, and difficulties occur in manufacturing the cosmetic formulation.

As another specific embodiment, the composition comprising the extract of milk thistle flower of the present invention is provided as a food composition for preventing or improving cell aging-related diseases or disorders.

The effect of preventing or improving the milk thistle flower extract of the present invention and its cellular aging-related diseases or disorders is as described above.

When the food composition is used as a food additive, the milk thistle flower extract may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment), and may further include a food pharmaceutically acceptable food supplement additive. The composition of the present invention is not only a material derived from a natural product, but also has confirmed its stability from a human safety test, so there is no great limitation on the amount of mixing.

The food composition of the present invention may include all foods in a conventional sense, and may be used interchangeably with terms known in the art, such as functional food and health functional food.

As used herein, the term "functional food" refers to food manufactured and processed using raw materials or ingredients useful for the human body according to Health Functional Food Act No. 6727, and "functionality" refers to the structure of the human body. And it means ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients for function or physiological action.

In addition, the term "health functional food" as used in the present invention refers to a food manufactured and processed using a specific ingredient as a raw material or by extracting, concentrating, refining, or mixing a specific ingredient contained in the food raw material for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., by the above ingredients, and the composition for health food is used for prevention of diseases and prevention of diseases. It can perform functions related to recovery, etc.

There is no limitation on the type of food in which the composition of the present invention can be used for the prevention or improvement of cellular aging-related diseases or disorders. In addition, the composition comprising the extract of milk thistle flower of the present invention as an active ingredient can be prepared by mixing other suitable auxiliary ingredients that may be contained in food and known additives according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and There are vitamin complexes and the like, and it can be prepared by adding the extract according to the present invention or a fraction thereof as a main component to juice, tea, jelly, juice, and the like.

In addition, foods that can be applied to the present invention include, for example, special nutritional foods (eg, formula milk, infant food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), health supplements , Seasoned foods (eg soy sauce, soybean paste, red pepper paste, mixed soy sauce, etc.), sauces, sweets (eg snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.) ), beverages (eg, fruit, vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).

The food composition comprising the milk thistle flower extract of the present invention as an active ingredient contains 0.0001 to 70.0 wt%, preferably 0.001 to 50.0 wt%, of the milk thistle flower extract based on the total weight of the composition. When the content of the milk thistle flower extract is less than 0.0001% by weight, the effect of removing senescent cells and restoring the function or shape of senescent cells like young cells to prevent and improve cell aging-related diseases cannot be expected, and 50.0% by weight If it is exceeded, the increase in the effect according to the content increase is insignificant, resulting in a problem in that the manufacturing cost increases.

When the food composition of the present invention is used in the form of a beverage, it may contain various sweetening agents, flavoring agents, natural carbohydrates, etc. as an additional component like a conventional beverage. In addition to the above, the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol , a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage.

In another aspect, the present invention provides a method for preventing, treating, or treating a cell aging-related disease or disorder, comprising administering a composition for preventing, treating, or ameliorating a cell aging-related disease or disorder comprising a milk thistle flower extract; or how to improve it.

The prevention, treatment, and improvement effects of the milk thistle flower extract and its cellular aging-related diseases or disorders are as described above. In addition, the "subject", "prevention", "treatment", and "improvement" are the same as described above.

The prevention, treatment, or improvement method of the present invention is specifically directed to the onset of senescent cell-related diseases or disorders caused by changes in the function and structure of tissues and/or organs due to the accumulation of senescent cells, increased senescence-related factors, etc. It may include administering the composition in an amount effective pharmaceutically, cosmetically, or foodologically to an individual who has been or is likely to develop the disease. The method of administration is the same as described above.

The composition comprising the milk thistle flower extract is the same as described above.

A suitable dosage of the composition of the present invention may vary depending on the patient's condition and weight, the degree of disease, drug form, and time, but may be appropriately selected by those skilled in the art.

The active ingredient of the present invention, milk thistle flower extract, has no skin irritation and is excellent in human safety, while cellular aging through the senolytic effect that selectively removes senescent cells and the senomorphic effect that restores the function and shape of senescent cells. It can be usefully used as a pharmaceutical composition, a cosmetic composition, and a food composition for the prevention, improvement, and treatment of related diseases. In particular, the composition comprising the extract of milk thistle flower of the present invention can prevent, treat, and improve chronic skin damage, obesity and diabetes, degenerative neurological disease, osteoarthritis, atherosclerosis, senile eye disease, tissue fibrosis disease, and skin aging. can be effectively applied for this purpose.

1 is a result showing the selective killing effect of senescent cells in a fibroblast replication senescence model by a milk thistle flower extract according to an embodiment of the present invention.
FIG. 2 is a diagram showing that milk thistle flower extract significantly increased apoptosis of senescent cells but did not induce apoptosis of young cells in a human fibroblast replicating aging model according to an embodiment of the present invention.
3 is a diagram showing that milk thistle flower extract has the effect of significantly increasing the expression of cleaved caspase-3 and cleaved PARP, which are apoptosis-related proteins, in a human fibroblast replication senescence model according to an embodiment of the present invention.
4 is a result of confirming the senomorphic action of milk thistle flower extract in aged human fibroblasts according to an embodiment of the present invention through SA-β-Gal activity staining. It is a figure showing the effect of reducing the increased SA-β-gal activity.
5 is a result of confirming the senomorphic action of the milk thistle flower extract in aged human fibroblasts according to an embodiment of the present invention by inhibiting the generation of MMP-1, an aging-related index, and the milk thistle flower extract is replicated. It is a figure showing the effect of inhibiting the production of MMP-1 in senescent cells.
6 is a result of confirming the senomorphic action of milk thistle flower extract in aged human fibroblasts according to an embodiment of the present invention by inhibiting the production of p-H2AX, p21, IL-6, and TNF-α. , A diagram showing that milk thistle flower extract has the effect of inhibiting the production of p-H2AX, p21, IL-6, and TNF-α in replicative senescent cells.

Hereinafter, examples and the like will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

Example 1: Preparation of Milk Thistle Flower Extract

After the milk thistle flowers from which the seeds were removed were thoroughly washed, dried in the shade at 20°C to 35°C, and then pulverized to a particle size of 1 mm or less. Then, 100 g of pulverized milk thistle flower powder was immersed in 70% ethanol solvent and ultrasonically extracted for 48 hours, and then the resulting extract was filtered using filter paper (Advantec, No. 2). The filtrate was concentrated under reduced pressure to prepare a milk thistle flower extract.

Example 2: Preparation of cloned senescent cells

In order to induce replication senescence, human dermal fibroblasts (HDFs) were purchased from ATCC (American Tissue Culture Collection, USA). After culturing human fibroblasts in DMEM medium supplemented with 10% FBS (fetal bovine serum), inoculated with 4 × 10 ⁵ cells in a 100 mm culture dish, and incubated with 5% CO ₂ in an incubator. Incubated at 37 °C conditions. When the cells grow to about 80-90% in the culture dish, the cells are removed by treatment with trypsin-EDTA, the number of cells is measured, and the cell population doubling time (DT) is measured according to Equation 1 below to confirm the degree of cell growth. did By successively subculturing the cells in the same manner as above, replication senescence was induced. The DT of young fibroblasts was 1.7 days, and the DT of replication-senescent fibroblasts was 9.7 days. The degree of cellular senescence was confirmed by senescence-associated beta-galactosidase staining or senescence-related markers (SASP) of MMP-1, p-H2AX, p21, IL-6, and TNF-α by ELISA and immunostaining.

[Equation 1]

DT= (TT ₀ ) / 3.32 × (logN-logN ₀ )

(N = number of cells grown in the culture dish, N ₀ = number of first seeded cells, T - T ₀ = number of days of cell culture)

Example 3: Confirmation of senolytic effect of milk thistle flower extract on human fibroblasts

In order to investigate the senolytic effect of milk thistle flower extract on human fibroblasts, the following experiment was conducted. Specifically, young cells or cloned senescent cells were treated with milk thistle flower extract at 50, 100, and 200 µg/mL, ABT737 at 10 µM concentration, and after culturing for 3 days, MTT reagent was added to each well at a concentration of 0.1 mg/mL. After 3 hours of incubation in an incubator, absorbance was measured at 570 nm using a microplate reader to confirm the degree of cell viability. The cell viability level was expressed as a relative value with the absorbance of the untreated control group being 100%.

In addition, the degree of increase in the young cell ratio of milk thistle flower extract by co-culturing young cells and cloned senescent cells was compared by labeling each cell so that it could be distinguished using Sigma-Aldrich's PKH Fluorescent Cell Linker. Specifically, fluorescently labeled cells were inoculated in a 6-well plate with young cells and cloned senescent cells in a ratio of 1 × 10 ⁴ : 1 × 10 ⁵ , and then in a 5% CO ₂ incubator at 37° C. for 24 hours. cultured. After that, milk thistle flower extract and ABT737 were treated at each concentration, and then cultured for 3 days at 37° C. in a 5% CO ₂ incubator. Thereafter, the cells were washed with 1x phosphate buffer and fixed with a 3.7% (v/v) paraformaldehyde solution. After nuclei were stained with Hoechst 33342 to confirm the total number of cells, the ratio of each cell was observed under a fluorescence microscope. ABT737 was used as a positive control as senolytics that selectively kill senescent cells. The results are shown in FIG. 1 .

As shown in Fig. 1a, cell viability of both substances was significantly reduced when ABT737 and milk thistle flower extract were treated compared to the control group in cloned senescent cells, but in young cells, when treated with milk thistle flower extract, the cytotoxicity was lower than that of ABT737. was found to be less.

In addition, as shown in Figure 1b, when young cells and cloned senescent cells were co-cultured with ABT737 and milk thistle flower extract, the milk thistle flower extract reduced cloned senescent cells, compared to the positive control ABT737, and It was confirmed that the percentage of young cells among the total cells was increased by maintaining the cells.

From the above results, it was confirmed that milk thistle flower extract acts as a senolytic agent that selectively kills by inducing specific apoptosis of replicative senescent cells in human fibroblasts.

Example 4: Selective apoptosis effect of milk thistle flower extract on senescent cells

As it has been reported that the senolytic effect is related to killing senescent cells through induction of apoptosis, the apoptosis-inducing effect of milk thistle flower extract in human fibroblasts was confirmed. First, in order to confirm the apoptosis-inducing effect of milk thistle flower extract, the degree of induction of Annexin V expression was checked. Specifically, young cells or senescent cells were inoculated at 1 × 10 ⁵ per well in a 6-well plate, and then cultured for 24 hours at 37° C. in a 5% CO ₂ incubator. Milk thistle flower extract was treated at 50, 100, and 200 μg/mL concentrations, and ABT737 was treated at 10 μM concentration, and then incubated at 37° C. in a 5% CO ₂ incubator for 3 days. Thereafter, the cells were washed with 1× phosphate buffer solution, and Annexin V staining solution containing 1 μg/mL PI was added, followed by reaction at room temperature for 15 minutes. After staining, Annexin V fluorescence was confirmed using a flow cytometer.

In addition, the expression levels of cleaved caspase-3 and cleaved PARP were confirmed through immunostaining to confirm the degree of influence of the milk thistle flower extract on the expression of apoptosis-related proteins. Specifically, young cells or cloned senescent cells were inoculated at 2 × 10 ⁴ per well in a 24-well plate, and then cultured for 24 hours at 37° C. in a 5% CO ₂ incubator. Thereafter, the cells were washed with 1x phosphate buffer and fixed with a 3.7% (v/v) paraformaldehyde solution. The fixed cells were treated with 5% Tween20 solution at room temperature for 1 hour, replaced with an antibody diluted solution containing cleaved caspase-3 and cleaved PARP primary antibody, and reacted at 4°C for 24 hours. Cells treated with primary antibody were washed 3 times with 1× phosphate buffer solution, treated with secondary antibody and reacted for 2 hours, washed 3 times with 1× phosphate buffer solution, and expression of cleaved caspase-3 and cleaved PARP The degree was confirmed with a fluorescence microscope. The results are shown in FIGS. 2 and 3 .

As shown in FIG. 2 , apoptosis was significantly increased in cloned senescent cells when treated with milk thistle flower extract and ABT737 compared to the control group, but in young cells, apoptosis was increased by ABT737 treatment, whereas milk thistle flower extract had no effect on apoptosis. It was confirmed that it was not given. In addition, as shown in FIG. 3 , it was confirmed that the milk thistle flower extract significantly increased the expression of apoptosis-related proteins, cleaved caspase-3 and cleaved PARP, in replication-senescent human fibroblasts compared to the control group, ABT737, a positive control. It was confirmed that the expression of apoptosis-related proteins increased more than

From the above results, it was confirmed that milk thistle flower extract acts as a senolytic agent that induces apoptosis in replicating senescent cells in human fibroblasts and increases the expression of related proteins to induce specific apoptosis of senescent cells.

Example 5: Confirmation of senomorphic effect of milk thistle flower extract on human fibroblasts

In order to investigate the senomorphic effect of milk thistle flower extract on human fibroblasts, the following experiment was conducted. Young cells or cloned senescent cells were treated with milk thistle flower extract at 50, 100, and 200 μg/mL and ABT737 at 10 μM and cultured for 3 days. 6, the degree of senescence of cells was confirmed by ELISA analysis or immunostaining of senescence-related indicators (SASP) such as p-H2AX, p21, and TNF-α. Specifically, young cells or senescent cells were inoculated into a 6-well plate at 1 × 105 cells per well, and then cultured for 24 hours at 37° C. in a CO2 incubator at a concentration of 5%. After treatment with each concentration of milk thistle flower extract and ABT737, cultured at 5% CO2 and 37°C for 3 days. Thereafter, the cells were washed with 1x phosphate buffer and fixed with a 3.7% (v/v) paraformaldehyde solution. After adding a staining solution containing 1 mg/ml X-gal, and reacting at 37° C. for 18 hours, cells with blue cytoplasm were identified using an optical microscope. In addition, the medium cultured for 3 days was centrifuged to remove by-products, the supernatant was removed, and the concentrations of MMP-1, p-H2AX, p21, IL-6, and TNF-α in the cell culture medium were checked through ELISA. The results are shown in FIGS. 4 to 6 .

As shown in FIG. 4 , it was confirmed that milk thistle flower extract and ABT737 reduced the increased SA-β-gal activity in replicative senescent cells. In addition, as shown in FIGS. 5 and 6, it was confirmed that the production of MMP-1, p-H2AX, p21, IL-6, and TNF-α, which are known as senescence-related indicators, was significantly reduced in replicative senescent cells.

From the above results, it was confirmed that milk thistle flower extract acts as a senomorphix capable of changing the function and shape of senescent cells into young cells in human fibroblasts.

Example 6: Safety Confirmation Experiment of Milk Thistle Flower Extract on Human Skin

In order to confirm that the milk thistle flower extract, which has been found to be excellent in the effect of removing senescent cells or changing the function and shape of senescent cells into young cells according to the present invention, is safe for human skin, skin containing milk thistle flower extract An external preparation was prepared and a skin safety verification experiment was performed by this.

An external preparation for skin containing 1% milk thistle flower extract of Example 1 was prepared with the component content shown in Table 1 below. To prepare an external preparation for skin, purified water, glycerin, and butylene glycol were mixed and dissolved at 70 ° C. (aqueous part), and the remaining components except for the three components and trimethanolamine were dissolved at 70 ° C (oil phase part). The oil part was added to the water phase part, and the mixture was first emulsified by stirring with a homomixer (Tokushu Kika, Japan), and trimethanolamine was finally added thereto. After removing the bubbles generated in the mixed solution, the mixture was cooled to room temperature to prepare an external preparation for skin.

ingredient content(%) control test group Purified water 72 71 glycerin 8.0 8.0 butylene glycol 4.0 4.0 Milk Thistle Flower Extract 0 1.0 Caprylic Capri Triglyceride 8.0 8.0 squalane 5.0 5.0 Cetearyl Glucuside 1.5 1.5 Sorbitan Stearate 0.4 0.4 cetearyl alcohol 1.0 1.0 trimethanolamine 0.1 0.1 gross weight 100 100

Measure whether or not the milk thistle flower extract stimulates the skin by applying a total of 9 24 hour cumulative patches every other day on the upper forearm to 30 healthy adults using each of the skin external preparations prepared as described above. did

The patching method used a pin chamber (Finn chamber, Epitest Ltd, Finland). After 15 μl of each of the above external skin preparations was dripped into the chamber, patching was performed. The degree of the reaction shown on the skin each time was scored using the following empirical formula 2, and the results are shown in Table 2 below.

[Empirical Formula 1]

Average reactivity = [[response index × reactivity / total number of subjects × highest score (4 points)] × 100] ÷ number of tests (9 times)

At this time, in the reactivity, ± is given a score of 1 point, + is 2 points, and ++ is 4 points, and when the average reactivity is less than 3, it was judged as a safe composition.

exam
matter Number of subjects who responded Average
reactivity 1 week 2 weeks 3 weeks Primary Secondary tertiary 4th 5th 6th 7th 8th 9th ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ control - - - - - - - - - - - - - - - - - - - - - - - - - - - 0.00 test group One - - One - - - - - - - - - - - - - - - - - - - - - - - 0.19 blood sword
personnel 30 30 30 30 30 30 30 30 30

In the case of the test group in Table 2, the number of persons corresponding to ±, +, and ++ was 1, 0, and 0, respectively, and the rest did not respond. When calculated according to the formula described above, [[(2 × 1)/(30 × 4)] × 100] ÷ 9 = 0.19, with an average reactivity of 0.19, so it is 3 or less, and skin including milk thistle flower extract (test group) Since the external application did not show a distinct cumulative irritation pattern like the control external application for skin, it was judged to be a safe material for human skin.

Preparation Example 1: Cosmetic formulation

Preparation Example 1-1: Softening lotion

As shown in Table 3 below, a softening lotion containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

ingredient weight% Milk Thistle Flower Extract 0.01 glycerin 3.0 butylene glycol 2.0 propylene glycol 2.0 carboxyvinyl polymer 0.1 ethanol 10.0 trimethanolamine 0.1 Preservatives, trace colors, trace fragrances and trace purified water 82.79 sum 100.0

Preparation Example 1-2: Nutrient lotion

Nutrient lotion containing milk thistle flower extract as an active ingredient as shown in Table 4 below was prepared according to a conventional method.

ingredient weight% Milk Thistle Flower Extract 0.01 beeswax 4.0 Polysrobate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 5.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 3.0 butylene glycol 3.0 propylene glycol 3.0 carboxyvinyl polymer 0.1 trimethanolamine 0.2 Preservatives, trace colors, trace fragrances and trace purified water 69.69 Total 0.0 100.0

Preparation Example 1-3: Nourishing Cream

As shown in Table 5 below, a nourishing cream containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

ingredient weight% Milk Thistle Flower Extract 0.01 beeswax 10.0 Polysrobate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 10.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 trimethanolamine 0.2 Preservatives, trace colors, trace fragrances and trace purified water 56.79 Total 0.0 100.0

Preparation Example 1-4: Massage Cream

As shown in Table 6 below, a nutritional cream containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

ingredient weight% Milk Thistle Flower Extract 0.01 beeswax 10.0 Polysrobate 60 1.5 Sorbitan sesquioleate 0.8 liquid paraffin 40.0 squalane 5.0 Caprylic/Capric Triglycerides 4.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 trimethanolamine 0.2 Preservatives, trace colors, trace fragrances and trace purified water 27.49 Total 0.0 100.0

Preparation Example 1-5: Pack

As shown in Table 7 below, a pack containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

ingredient weight% Milk Thistle Flower Extract 0.01 polyvinyl alcohol 13.0 Sodium Carboxymethylcellulose 0.2 allatoin 0.1 ethanol 5.0 nonylphenyl ether 0.3 Preservatives, trace colors, trace fragrances and trace purified water 81.39 Total 0.0 100.0

Preparation Example 2: Pharmaceutical formulation

Preparation Example 2-1: Preparation of powder

ingredient content (g) Milk Thistle Flower Extract 2 lactose One

The above ingredients were mixed and filled in an airtight cloth to prepare a powder.

Preparation Example 2-2: Preparation of tablets

ingredient Content (mg) Milk Thistle Flower Extract 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the ingredients in Table 9, tablets were prepared by tableting according to a conventional method for manufacturing tablets.

Preparation 2-3: Preparation of capsules

ingredient Content (mg) Milk Thistle Flower Extract 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the ingredients in Table 10, the capsules were prepared by filling in gelatin capsules according to a conventional manufacturing method of capsules.

Preparation Example 2-4: Preparation of gel

ingredient weight% Milk Thistle Flower Extract 1.00 Butylene Glycol 2.00 glycerin 1.00 Disodium EDT 0.02 PEG-60-Hydrogenated Castor Oil 1.00 Cocamidopropyl Betaine 4.00 Lauryl Glucoside 6.00 Flosorbate 20 1.00 Sodium Benzoate 0.40 caprylic glycol 0.20 sodium lactate 0.50 Hydroxyethyl Cellulose 0.7 Purified water 82.18 sum 100.0

After mixing the ingredients in Table 11, a gel containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

Preparation Example 2-5: Preparation of ointment

ingredient weight% Milk Thistle Flower Extract 1.0 diethanolamine 1.5 polyvinyl prorolidone 5.0 propylene glycol 30.0 Purified water 62.5 sum 100.0

After mixing the ingredients in Table 12, an ointment containing milk thistle flower extract as an active ingredient was prepared according to a conventional method.

Preparation Example 3: Preparation of food

Preparation Example 3-1: Preparation of wheat flour food

0.5 to 5.0 parts by weight of the milk thistle flower extract of the present invention was added to wheat flour, and bread, cakes, cookies, crackers and noodles were prepared using this mixture.

Preparation Example 3-2: Preparation of soups and gravies

By adding 0.1 to 5.0 parts by weight of the milk thistle flower extract of the present invention to soup and broth, processed meat products for health promotion, soup and broth of noodles were prepared.

Preparation 3-3: Preparation of ground beef

Ground beef for health promotion was prepared by adding 10 parts by weight of the milk thistle flower extract of the present invention to ground beef.

Preparation 3-4: Preparation of dairy products

5-10 parts by weight of the milk thistle flower extract of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

Preparation 3-5: Preparation of sausage

A sausage food composition comprising the milk thistle flower extract of the present invention was prepared as follows. 65.18% by weight of pork, 25% by weight of chicken meat, 3.5% by weight of starch, 1.7% by weight of soybean protein, 1.62% by weight of salt, 1.4% by weight of glucose, 1.5% by weight of glycerin, and 0.1% by weight of milk thistle flower extract by a conventional method sausage was prepared.

Preparation Example 3-6: Preparation of health drinks

Additive ingredients such as high fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), and water (75%) and 5 g of the milk thistle flower extract of the present invention are homogeneously mixed for instantaneous After sterilization, it was prepared by packaging it in a small packaging container such as a glass bottle or a plastic bottle.

Preparation Example 3-7: Preparation of vegetable juice

Vegetable juice was prepared by adding 5 g of the milk thistle flower extract of the present invention to 1,000 ml of tomato or carrot juice.

Preparation Example 3-8: Preparation of fruit juice

Fruit juice was prepared by adding 1 g of the milk thistle flower extract of the present invention to 1,000 ml of apple or grape juice.

Claims (9)

A pharmaceutical composition for preventing or treating cell aging-related diseases or disorders, comprising a milk thistle flower extract as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the prevention or treatment of the cellular aging-related disease or disorder is by senolytics that selectively removes senescent cells and senomorphix that restores the function and shape of senescent cells. .
According to claim 1, wherein the cell aging-related disease or disorder is a neurodegenerative disease or disorder; cardiovascular disease or disorder; metabolic disease or disorder; lung disease or disorder; inflammatory or autoimmune diseases or disorders; transplant related disease or disorder; eye disease or disorder; proliferative disease or disorder; chemotherapy and radiotherapy side effects; geriatric diseases or disorders; fibrotic disease or disorder; skin disease or disorder; And a disease or disorder according to the aging of stem cells; Pharmaceutical composition, characterized in that any one or more selected from the group consisting of.
A cosmetic composition for preventing or improving cell aging-related skin diseases or disorders, comprising a milk thistle flower extract as an active ingredient.
The cosmetic composition according to claim 4, wherein the prevention or improvement of the cellular aging-related skin disease or disorder is by senolytics that selectively removes senescent cells and senomorphix that restores the function and shape of senescent cells. .
5. The method of claim 4, wherein the cell aging-related skin disease or disorder is psoriasis, eczema, wrinkles, loss of elasticity, pruritus, sensory disturbance, papular dystonia, erythroderma, lichen planus, lichenoid dermatosis, nevus, rash, urticaria, Atopic dermatitis, eosinophilic dermatosis, reactive neutrophil dermatosis, pemphigus, pemphigoid, immune bullous dermatosis, dermal fibrous histiocytosis, dermatolymphoma, dermal lupus, hyperpigmentation, scar, keloid, strawberry nose, vitiligo, ichthyosis, dermatomyositis , age spots, blemishes, freckles, spots, and cosmetic composition, characterized in that any one or more selected from the group consisting of actinic keratosis.
A food composition for preventing or improving cell aging-related diseases or disorders, comprising a milk thistle flower extract as an active ingredient.
The food composition according to claim 7, wherein the prevention or improvement of the cell aging-related disease or disorder is by senolytics that selectively removes senescent cells and senomorphix that restores the function and shape of senescent cells.
The method of claim 7, wherein the cell aging-related disease or disorder is a neurodegenerative disease or disorder; cardiovascular disease or disorder; metabolic disease or disorder; lung disease or disorder; inflammatory or autoimmune diseases or disorders; transplant related disease or disorder; eye disease or disorder; proliferative disease or disorder; chemotherapy and radiotherapy side effects; geriatric diseases or disorders; fibrotic disease or disorder; skin disease or disorder; And a disease or disorder according to the aging of stem cells; Food composition, characterized in that any one or more selected from the group consisting of.

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