WO2021006684A1 - Procédé de préparation d'un extrait de levure ultrasoniqué ayant une excellente activité inhibitrice contre le cancer de la peau et composition inhibant le cancer de la peau comprenant un extrait de levure ultrasoniqué préparé par le même procédé - Google Patents
Procédé de préparation d'un extrait de levure ultrasoniqué ayant une excellente activité inhibitrice contre le cancer de la peau et composition inhibant le cancer de la peau comprenant un extrait de levure ultrasoniqué préparé par le même procédé Download PDFInfo
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- WO2021006684A1 WO2021006684A1 PCT/KR2020/009065 KR2020009065W WO2021006684A1 WO 2021006684 A1 WO2021006684 A1 WO 2021006684A1 KR 2020009065 W KR2020009065 W KR 2020009065W WO 2021006684 A1 WO2021006684 A1 WO 2021006684A1
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- skin cancer
- ultrasonic
- yeast
- yeast extract
- extract
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/218—Yeast extracts
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2300/00—Processes
- A23V2300/48—Ultrasonic treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/82—Preparation or application process involves sonication or ultrasonication
Definitions
- the present invention relates to a composition for improving, preventing or treating skin cancer comprising an ultrasonic yeast extract.
- Skin cancer increases the chance of exposure to various harmful substances or ultraviolet rays due to changes in life patterns such as increased outdoor activities and the increase in the amount of ultraviolet rays due to the destruction of the ozone layer due to environmental pollution. As the aging population increases, the number of patients continues to increase worldwide.
- basal cell carcinoma accounts for about 80%
- squamous cell carcinoma BCC
- SCC squamous cell carcinoma
- melanoma which corresponds to about 4%
- Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are collectively referred to as nonmelanoma skin cancer (NMSC).
- Melanoma arises from melanocytes in the epidermis, most of which are metastatic cancers or carcinomas that lead to death.In 2000, 47,000 people were identified as new melanomas, of which 7,700 were reported to have died (RT Greenlee et al. al. Cancer J. Clin., 50: 7-33, 2000).
- melanoma may be caused by chronic exposure to ultraviolet rays, but is expected to occur due to intermittent exposure such as extreme sun tanning. Because melanoma has a worse prognosis than other skin cancers, recurrence is common even if detected early and can shorten life. Skin lesions appear as yellowish brown or black spots or nodules, and usually occur after middle age by sun exposure. Sometimes it occurs in the ends of the hands and toes, especially the thumb and toe, and black vertical lines may be seen on the nails. In this case, melanoma should be suspected and a thorough investigation should be conducted.
- An object of the present invention is to provide a cosmetic composition for preventing or improving skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- Another object of the present invention is to provide a food composition for preventing or improving skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- Another object of the present invention is to provide a pharmaceutical composition for preventing or treating skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- Another object of the present invention is to provide a method for preventing or treating skin cancer comprising administering a therapeutically effective amount of an ultrasonic yeast extract to an individual.
- Another object of the present invention is to provide the use of an ultrasonic yeast (yeast) extract to produce a pharmaceutical formulation having a preventive or therapeutic effect of skin cancer.
- yeast ultrasonic yeast
- Another object of the present invention is to provide a method for preparing an ultrasonic yeast extract comprising the step of adding an aqueous sodium hydroxide (NaOH) solution to yeast and treating ultrasonic waves.
- an aqueous sodium hydroxide (NaOH) solution to yeast and treating ultrasonic waves.
- the present invention provides a cosmetic composition for preventing or improving skin cancer comprising an ultrasonic yeast (yeast) extract as an active ingredient.
- yeast ultrasonic yeast
- the present invention provides a food composition for preventing or improving skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing or treating skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- the present invention provides a method for preventing or treating skin cancer comprising administering a therapeutically effective amount of an ultrasonic yeast extract to an individual.
- the present invention provides a method for preparing an ultrasonic yeast extract comprising the step of adding an aqueous sodium hydroxide (NaOH) solution to yeast and treating ultrasonic waves.
- aqueous sodium hydroxide (NaOH) solution to yeast and treating ultrasonic waves.
- the ultrasonic yeast extract according to the present invention has excellent activity of inhibiting the proliferation of skin cancer cells, and thus can be usefully used in the manufacture of cosmetics, functional foods and pharmaceuticals for the prevention, improvement or treatment of skin cancer.
- 1 is a result of analyzing the cell proliferation inhibitory ability of the yeast ultrasonic extract prepared according to each extraction condition for skin cancer cell lines.
- the present invention provides a composition for preventing, improving or treating skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- the yeast may be Saccharomyces cerevisiae .
- the skin cancer is composed of melanoma, papilloma, carcinoma, squamous cell carcinoma, basal cell carcinoma, and spindle cell carcinoma. It may be selected from the group, but is not limited thereto.
- the present invention provides a method for producing an ultrasonic yeast extract having an activity capable of effectively inhibiting the proliferation of skin cancer cells.
- the yeast ultrasonic extract is prepared by treating yeast with ultrasonic waves.
- the ultrasonic extract of yeast obtained by performing the treatment of aqueous sodium hydroxide (NaOH) and ultrasonic treatment together has excellent skin cancer inhibitory activity.
- aqueous sodium hydroxide (NaOH) solution was added and It was confirmed that the extract obtained by ultrasonic treatment at 95° C. for 1.5 to 2.5 hours has the best skin cancer inhibitory activity.
- the present invention can provide a method for preparing an ultrasonic yeast extract having skin cancer inhibitory activity, and preferably, the method comprises adding 0.1M to 0.2M sodium hydroxide (NaOH) aqueous solution to the yeast, and 85°C to 95°C It may include the step of ultrasonic treatment for 1.5 hours to 2.5 hours.
- the method comprises adding 0.1M to 0.2M sodium hydroxide (NaOH) aqueous solution to the yeast, and 85°C to 95°C It may include the step of ultrasonic treatment for 1.5 hours to 2.5 hours.
- 0.2M sodium hydroxide (NaOH) aqueous solution is added to the yeast and ultrasonicated at 90° C. for 2 hours to obtain an ultrasonic yeast extract having excellent skin cancer inhibitory activity.
- the concentration of sodium hydroxide (NaOH) is less than 0.1M, there is a problem that extraction of an extract containing a physiologically active substance having skin cancer inhibitory activity from yeast is insufficient, whereas it exceeds 0.2M.
- the concentration of sodium hydroxide (NaOH) should be used in the range of 0.1M to 0.2M, and most preferably, the concentration of 0.2M can be used.
- the extraction temperature is performed at less than 85°C during the ultrasonic extraction of the present invention, as confirmed in an embodiment of the present invention, there is a problem that the skin cancer inhibiting activity of the ultrasonic yeast extract is insufficient, and at a temperature exceeding 95°C If performed, the active ingredient may be destroyed or denatured, which may also cause a decrease in skin cancer inhibitory activity.
- the extraction time may be performed in 1.5 hours to 2.5 hours.
- the ultrasonic yeast extract obtained by the method of the present invention has excellent anticancer activity against skin cancer.
- the ability to inhibit cell proliferation of the melanoma cell line was analyzed, and 0.2M sodium hydroxide (NaOH) aqueous solution was used.
- NaOH sodium hydroxide
- the present inventors analyzed the protein expression changes of c-myc and cyclin D1 in cells according to the treatment of the ultrasonic yeast extract of the present invention in order to determine through which mechanism the skin cancer inhibitory activity of the ultrasonic yeast extract of the present invention occurs. I did.
- the expression of c-myc in the group treated with the ultrasonic yeast extract of the present invention did not show any change in the expression level compared to the group not treated with the extract, but the expression level of the cyclin D1 protein was significantly decreased.
- the present invention provides a cosmetic composition for preventing or improving skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- the composition may be prepared in a liquid or solid form using bases, auxiliary agents and additives commonly used in the cosmetic field.
- Cosmetics in a liquid or solid form may include, for example, but not limited to, a form such as a lotion, cream, lotion, and bath agent.
- the composition of the present invention may include not only an ultrasonic yeast extract, but also ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, pigments And conventional adjuvants such as fragrances, and carriers.
- ingredients commonly used in cosmetic compositions such as antioxidants, stabilizers, solubilizers, vitamins, pigments And conventional adjuvants such as fragrances, and carriers.
- the cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleaning, It may be formulated as an oil, powder foundation, emulsion foundation, wax foundation, and spray, but is not limited thereto. In more detail, it may be prepared in the form of a flexible lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
- the present invention provides a food composition for preventing or improving skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- a health food it can be prepared in the form of tea, juice, and drinks using the ultrasonic yeast extract of the present invention and consumed, or granulated, encapsulated, and powdered.
- it may be prepared in the form of a composition by mixing with known substances or active ingredients known to have an effect of preventing or improving skin cancer.
- functional foods include beverages (including alcoholic beverages), fruits and processed foods thereof (eg, canned fruit, canned food, jam, marmalade, etc.), fish, meat and processed foods thereof (eg, ham, sausage corn beef, etc.) ), breads and noodles (e.g. udon, soba, ramen, spaghetti, macaroni, etc.), fruit juice, various drinks, cookies, syrup, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine, vegetable protein, It can be prepared by adding the active ingredient of the present invention to retort foods, frozen foods, various seasonings (eg, miso, soy sauce, sauce, etc.).
- beverages including alcoholic beverages
- fruits and processed foods thereof eg, canned fruit, canned food, jam, marmalade, etc.
- fish e.g. ham, sausage corn beef, etc.
- breads and noodles e.g. udon, soba, ramen, spaghetti, macaroni, etc.
- fruit juice e
- the preferred content of the active ingredient of the present invention in the food composition of the present invention is not limited thereto, but may preferably be contained in a solid content of 0.01 to 50% by weight in the finally prepared food.
- the composition of the present invention may be prepared and used in the form of a powder or a concentrate.
- the present invention provides a pharmaceutical composition for preventing or treating skin cancer comprising an ultrasonic yeast extract as an active ingredient.
- the pharmaceutical composition is a tablet, capsule, pill, granule, powder, extract, suspension, emulsion, syrup, aerosol oral form, formulation, ointment, coating, or intravenous, intramuscular, subcutaneous, cerebrovascular It can be prepared in the form of a sterile injectable solution or suppository for administration.
- the pharmaceutical dosage form of the pharmaceutical composition of the present invention can be combined with an appropriate carrier that is generally acceptable for the manufacture of pharmaceutical compositions to be used in a conventional method. It can be formulated in various forms.
- Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include dextrose, lactose, sucrose, starch, sorbitol, mannitol, xylitol, gum acacia, calcium silicate, calcium phosphate, alginate, gelatin, cellulose , Methyl cellulose, microcrystalline cellulose, water, propylhydroxybenzoate, mineral oil, methylhydroxybenzoate, talc, magnesium stearate, and the like.
- it can be prepared by using diluents or excipients such as commonly used binders, disintegrants, fillers, extenders, surfactants, and wetting agents.
- Solid preparations for oral administration include tablets, capsules, pills, granules, powders, and the like, and these solid preparations contain at least one excipient, such as starch, sucrose or lactose, gelatin, etc. in the active ingredient of the present invention. It is prepared by mixing.
- Injections in the form of solutions or suspensions for parenteral administration may be administered subcutaneously, intravenously, intramuscularly, or intraperitoneally.
- the coating agent can be easily prepared in various forms such as cream, ointment, suspension, and emulsion according to a conventional manufacturing method.
- the active ingredient of the present invention is contained in a general water-in-water type or water-in-oil type base, and flavors, chelating agents, coloring agents, antioxidants, preservatives, etc. can be used as needed, and the purpose of improving physical properties Vitamins, proteins, minerals, etc. can be used in combination.
- the dosage of the active ingredient may be changed according to the weight of the patient, the severity of the disease, the drug formulation, the state of health, the route of administration, and the administration period. For a desirable effect, it is good to administer 0.001 to 10 g/kg per day, preferably 0.01 to 0.1 g/kg, but is not limited thereto. Administration can be administered once a day or divided into several times.
- the present invention provides a method for preventing or treating skin cancer comprising administering a therapeutically effective amount of an ultrasonic yeast extract to an individual.
- the therapeutically effective amount is a specific composition including the type and degree of the reaction to be achieved, whether or not other agents are used in some cases, the individual's age, weight, general health status, sex and diet, administration time, administration route and composition. It is preferable to apply differently depending on various factors including the secretion rate of the drug, the treatment period, drugs used with or concurrently with the specific composition, and similar factors well known in the medical field. Therefore, it is preferable to determine an effective amount of a composition suitable for the purposes of the present invention in consideration of the foregoing.
- the individual is applicable to any mammal, and the mammal includes humans and primates, as well as livestock such as cattle, pigs, sheep, horses, dogs and cats.
- the present invention provides the use of an ultrasonic yeast (yeast) extract to produce a pharmaceutical formulation having a preventive or therapeutic effect of skin cancer.
- yeast ultrasonic yeast
- the present inventors prepared an ultrasonic yeast extract by varying the following extraction conditions.
- an aqueous solution in which NaOH was dissolved in each concentration (0.15 and 0.2M) was added to yeast in powder form (Saccharomyces cerevisiae; purchased from Celltech Co., Ltd.) (10 times the amount of yeast (w/v)).
- yeast in powder form Sacharomyces cerevisiae; purchased from Celltech Co., Ltd.
- Addition) and hourly (1hr, 3hr, 5hr) ultrasonic treatment to prepare an ultrasonic extract, wherein the ultrasonic treatment conditions were 20 kHz, 80% amplitude, 750 W, pulse 20 s on/10 s off, and temperature was extracted by differently at 90°C, 70°C and 50°C, respectively.
- each yeast ultrasonic extract obtained in Example 1 was treated with each yeast ultrasonic extract, and then the degree of cell proliferation was analyzed.
- Each sample used in the cell proliferation analysis is shown in Table 1 below.
- B16F10 melanoma cell line was dispensed at 4 x 10 3 cells per well in a 96 well plate, and each ultrasonic extract was treated at various concentrations 3 hours after the cell dispensing, and then for 3 days under conditions of 37°C and 5% CO 2 During incubation. After incubation for 3 days, live cells were colored using Promega CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay (MTS) reagent to measure the degree of cell proliferation.
- MTS Non-Radioactive Cell Proliferation Assay
- the yeast ultrasonic extract (#2 ⁇ #13) obtained by ultrasonic treatment had a better inhibitory effect on the proliferation of melanoma cells compared to the control (control, #1) obtained by the alkaline extraction method without ultrasonic treatment.
- the yeast ultrasonic extracts (#10, #11) obtained by ultrasonic treatment at 90°C for 2 hours in 0.2M aqueous NaOH solution have a remarkable effect of inhibiting cell proliferation of melanoma cell lines compared to extracts obtained under other conditions. Confirmed (Fig. 1).
- the ultrasonic yeast extract of the present invention obtained under the above conditions was compared to the extract obtained using a 0.15M NaOH aqueous solution having a concentration lower than 0.2M and an extract obtained using a 0.5M NaOH aqueous solution having a concentration higher than 0.2M. It was confirmed that the cell proliferation inhibitory activity of skin cancer cell lines was remarkable.
- Example 2 From the results of Example 2, it was confirmed that the ultrasonic yeast extract has a remarkable effect on anticancer activity against skin cancer. Accordingly, the present inventors conducted an experiment to confirm the effect of the ultrasonic yeast extract on the intracellular mechanism on the inhibition of skin cancer.
- c-myc is known to be an oncogene
- Cyclin D1 is known to be overexpressed in cancer cells.
- the present inventors confirmed changes in the expression levels of c-myc and Cyclin D1 proteins in melanoma cell lines through Western blot when the yeast ultrasonic extract was treated.
- the ultrasonic yeast extract has the effect of remarkably suppressing the expression of the Cyclin D1 protein compared to the control (FIG. 2).
- the extract obtained by sonicating at 90°C for 2 hours in an aqueous NaOH solution of 0.15M and 0.2M concentration was obtained under different conditions (0.2M NaOH aqueous solution, 3 hours, ultrasonic treatment at 70°C; or 0.2M NaOH)
- Fig. 2 It was confirmed that there is an effect of remarkably suppressing the expression of Cyclin D1 protein compared to aqueous solution, 3 hours, sonication at 50°C)
- Fig. 2 there was no effect on the expression of c-myc (Fig. 2).
- the present inventors performed an experiment to analyze the tumor size and the expression level of Cyclin D1 in the tumor tissue by treating the ultrasonic yeast extract in an animal model. Briefly, 6 week old BALB/c-nu mice were used in the experiment, and mice were acclimated for 1 week after purchase. Thereafter, the B16F10 melanoma cell line (cell number: 5 ⁇ 10 5 cells) was injected into the dorsal skin tissue of each mouse. After confirming that tumors were formed in the dorsal skin tissue of the mouse, the yeast ultrasound extract (500 mg/kg body weight) was administered intraperitoneally once every 2 days. Tumor size was analyzed 0, 2, 4 and 6 days after administration of the yeast ultrasound extract, and changes in the expression of Cyclin D1 protein in the tumor tissue were measured by Western blot 6 days after administration of the yeast ultrasound extract.
- the present inventors confirmed that the ultrasonic yeast extract has a remarkable effect on anticancer activity even in an animal model of skin cancer.
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Abstract
La présente invention concerne: une composition comprenant un extrait de levure ultrasoniqué pour la prévention, le soulagement ou le traitement du cancer de la peau; et son procédé de préparation, l'extrait de levure ultrasoniqué ayant une activité inhibitrice remarquable contre la prolifération de cellules cancéreuses de la peau et pouvant être avantageusement utilisé dans les domaines cosmétiques, fonctionnels et médicinaux.
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WO1991007091A1 (fr) * | 1989-11-09 | 1991-05-30 | Donzis Byron A | Extrait de levure insoluble |
KR20040082060A (ko) * | 2003-03-18 | 2004-09-24 | 주식회사 바이오프로젠 | 효모변이주 아이에스투 유래 수용성 글루칸 올리고머를함유하는 면역활성용 또는 암질환 예방 및 치료용 조성물,및 이의 제조방법 |
KR20170055327A (ko) * | 2015-11-11 | 2017-05-19 | (주)엠앤씨생명과학 | 사카로미세스속 효모 추출물을 포함하는 천연 리포좀, 그 제조방법 및 이를 포함하는 식품 또는 약학 조성물 |
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KR101365735B1 (ko) | 2012-04-19 | 2014-02-21 | 부산대학교 산학협력단 | 효모로 발효된 마늘의 헥산 추출물을 포함하는 혈액종양의 예방 또는 치료용 의약 조성물 |
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WO1991007091A1 (fr) * | 1989-11-09 | 1991-05-30 | Donzis Byron A | Extrait de levure insoluble |
KR20040082060A (ko) * | 2003-03-18 | 2004-09-24 | 주식회사 바이오프로젠 | 효모변이주 아이에스투 유래 수용성 글루칸 올리고머를함유하는 면역활성용 또는 암질환 예방 및 치료용 조성물,및 이의 제조방법 |
KR20170055327A (ko) * | 2015-11-11 | 2017-05-19 | (주)엠앤씨생명과학 | 사카로미세스속 효모 추출물을 포함하는 천연 리포좀, 그 제조방법 및 이를 포함하는 식품 또는 약학 조성물 |
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DEJUAN, HUANG ET AL.: "The research for the extraction of yeast’s nucleic acid with [BMIM] BF4-H2O-KH2PO4 ionic liquid aqueous two-phase system", ADVANCED MATERIALS RESEARCH, vol. 455-456, 2012, pages 477 - 482 * |
ELWAKKAD AMANY, GHONEUM MAMDOOH, EL-SAWI MAMDOUH, MOHAMED SAADIA IBRAHIM, GAMAL EL DIN AMINA A., PAN DEYU, ELQATTAN GHADA MAHMOUD,: "Baker’s yeast induces apoptotic effects and histopathological changes on skin tumors in mice", COGENT MEDICINE, vol. 5, no. 1, 1 January 2018 (2018-01-01), pages 1437673, XP055772404, DOI: 10.1080/2331205X.2018.1437673 * |
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