WO2021096098A1 - Composition contenant un extrait de melon d'hiver en tant que principe actif pour augmenter la santé osseuse - Google Patents

Composition contenant un extrait de melon d'hiver en tant que principe actif pour augmenter la santé osseuse Download PDF

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Publication number
WO2021096098A1
WO2021096098A1 PCT/KR2020/014640 KR2020014640W WO2021096098A1 WO 2021096098 A1 WO2021096098 A1 WO 2021096098A1 KR 2020014640 W KR2020014640 W KR 2020014640W WO 2021096098 A1 WO2021096098 A1 WO 2021096098A1
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Prior art keywords
bone
extract
active ingredient
copper
fruit extract
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PCT/KR2020/014640
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English (en)
Korean (ko)
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조주현
강준철
조현덕
이다영
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주식회사 하람
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Publication of WO2021096098A1 publication Critical patent/WO2021096098A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
    • A23L5/20—Removal of unwanted matter, e.g. deodorisation or detoxification
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • 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
    • A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention

Definitions

  • the present invention relates to a composition for improving bone health comprising a copper fruit extract as an active ingredient, and can be used as a variety of uses, such as pharmaceuticals and foods.
  • Food contains substances necessary to maintain human life phenomena, and humans maintain life by ingesting food, digesting it in the digestive system, absorbing it, and supplying it to the tissue cells in the body.
  • Nutrition directly and indirectly causes diseases, and is known to be involved in the prevention and treatment of diseases.
  • the lack of nutrients caused by poorly balanced intake of nutrients necessary for the human body is a problem, and excessive intake is also a serious problem. , This can cause various diseases.
  • Health promotion is aimed at increasing resistance to diseases, especially chronic degenerative diseases or infections, continuous stress, and increasing daily activity. To this end, improving nutrition, strengthening immune function, proper exercise and rest, and mental activity. Management that affects the overall lifestyle, such as sustainability, is required.
  • growth is defined in a broad sense, it can be said that it includes not only an increase in height but also an increase in the size and function of each organ in the body.
  • the increase in kidney is achieved through skeletal metabolism, including the synthesis of cartilage tissue, skeletal length growth, and extensive proliferation of skeletal tissue by various factors such as nutrition and growth hormone.
  • Bone ( ⁇ ) tissue is a specially differentiated form of connective tissue, which is a connective tissue composed of several types of cells such as mesenchymal cells, chondrocytes, osteoblasts, osteoclasts, and bone marrow cells.
  • a balance is maintained between the amount of bone resorption by osteoclasts and the amount of bone formation by osteoblasts.
  • the bone formation ability by the osteoblasts reaches its peak and the amount of bone formation far exceeds the amount of bone resorption, so bone growth is achieved.
  • growth hormone therapy which was used for poor growth in a pathological condition in the past, has been applied to growing children and adolescents with normal height as interest in height growth has increased in recent years.
  • the administration of the growth hormone formulation has excellent effects in the case of people who are deficient in growth hormone, but in the majority of people with normal hormone secretion, various side effects such as acromegaly, positive growth hormone antibody, systemic allergic reaction, hypothyroidism, etc. There is a problem that can cause.
  • the copper fruit extract can help improve bone health by promoting the differentiation of osteoblasts involved in bone formation.
  • the present invention is to solve the problems of the prior art described above, an object of the present invention is to provide a functional food drug derived from a natural plant excellent in biosafety.
  • a food composition for improving bone health comprising a copper fruit extract as an active ingredient.
  • the extract may be extracted with water, alcohol, ethyl acetate, acetone, nucleic acid, dichloromethane, or a mixed solvent thereof.
  • a food composition for promoting growth comprising a copper fruit extract as an active ingredient.
  • a food composition for preventing or improving bone disease comprising a copper fruit extract as an active ingredient.
  • the bone disease may be one or more selected from the group consisting of osteoporosis, bone insufficiency, osteomalacia, bone mass reduction, fracture, bone defect, and hip joint reduction.
  • a pharmaceutical composition for promoting growth or improving bone health comprising a copper fruit extract as an active ingredient.
  • a pharmaceutical composition for preventing or treating bone diseases comprising a copper fruit extract as an active ingredient.
  • the bone disease may be one or more selected from the group consisting of osteoporosis, bone insufficiency, osteomalacia, bone mass reduction, fracture, bone defect, and hip joint reduction.
  • composition according to an aspect of the present invention includes a natural extract as an active ingredient, so that it is not only excellent in biosafety, but also has excellent bone health improvement effects, so it can be usefully used as a health functional food as well as a bone disease treatment.
  • Figure 2 is a result of evaluating the osteoblast differentiation promoting activity of the copper fruit extract according to an embodiment of the present invention.
  • (A) is a copper and hot water extract
  • (B) is a copper and ethanol extract.
  • FIG. 3 and 4 are results of evaluating the ALP activity of the copper fruit extract according to an embodiment of the present invention.
  • (A) is a copper and hot water extract
  • (B) is a copper and ethanol extract.
  • the numerical range includes the numerical values defined in the above range. All maximum numerical limits given throughout this specification include all lower numerical limits as if the lower numerical limits were expressly written. All minimum numerical limits given throughout this specification include all higher numerical limits as if the higher numerical limits were expressly written. All numerical limits given throughout this specification will include all better numerical ranges within the wider numerical range, as if the narrower numerical limits were expressly written.
  • a food composition for preventing or improving bone disease comprising a copper fruit extract as an active ingredient.
  • the "winter melon" is an annual vine plant of the gourd family and is also called Dong-A or Fairy Tale, and its scientific name is Benincasa hispida , Benincasa cerifera , Benincasa cerifera Savi Etc.
  • the bone disease refers to a condition or disease in which an increase in bone mass is required or required through promoting the activity of osteoblasts or inhibiting the activity of osteoclasts, and may be, for example, a metabolic bone disease or an orthopedic bone disease. .
  • the “metabolic bone disease” refers to a condition or disease that appears due to excessive production or activity of osteoclasts, and may include a bone mass-lowering disease.
  • the bone mass-lowering disease refers to a condition or disease in which bone mass decreases accompanied by symptoms such as a decrease in bone density and softening of bone tissue.
  • the bone disease may be one or more selected from the group consisting of osteoporosis, bone insufficiency, osteomalacia, bone mass loss, fracture, bone defect, and hip joint loss, but is not limited thereto.
  • the "contained as an active ingredient” means containing an amount sufficient to provide a therapeutic or prophylactic effect to the individual to be administered, and the copper fruit extract is excellent in biosafety, so those skilled in the art can appropriately set the upper limit of the quantity. Can be adjusted.
  • extract refers to a solvent in which the active ingredient contained in the raw material for extraction is transferred by contacting the solvent with the raw material for extraction under specific conditions. You can include all regardless. For example, it may include extracting a component soluble in a solvent from a natural product using water or an organic solvent, and extracting a specific component of a natural product, such as extracting only a specific component such as an oil.
  • the extract can be obtained by drying and powdering the copper fruit, or by various extraction methods known in the art such as hot water extraction and ethanol extraction.
  • the extract may be extracted with water, alcohol, ethyl acetate, acetone, nucleic acid, dichloromethane, or a mixed solvent thereof, and preferably may be extracted with ethanol at a concentration of 60 to 90% (w/w).
  • the extraction ratio of the active ingredient contained in the raw material may be different depending on the polarity of the solvent, it may be varied in consideration of the selectivity of the physiologically active substance according to the solvent.
  • the extract is extracted by conventional methods such as reflux extraction, pressure extraction, ultrasonic extraction, etc. for about 1 to 24 hours with a solvent having a volume of 8 to 12 times the weight of the raw material by washing the extraction raw material with water, drying and grinding, and It can be prepared by filtration.
  • the extract can be obtained in powder form by an additional process such as distillation under reduced pressure or freeze drying.
  • the extract may also include an extract that has undergone a conventional purification process.
  • the extract may be subjected to various additional purification methods, such as separation using an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatography (one prepared for separation according to size, charge, hydrophobicity, or affinity). It may contain a fraction obtained through.
  • the food composition may be used for promoting growth or improving bone health.
  • the “growth” may mean not only an increase in height, but also an increase in the anatomical and morphological size and function of each organ of the body, that is, the development of functions and differentiation into organs.
  • the food composition including copper fruit extract, can grow bone length, promote the metabolism of growth plate cartilage cells, and so forth, without side effects, and can bring about excellent growth promoting effect, so that it can be particularly useful as a food material for promoting children's growth.
  • the “bone health” refers to normal bone decomposition and remodeling, and bone-related diseases such as osteoporosis and osteoarthritis may occur if the balance of bone decomposition and remodeling is broken due to insufficient calcium in the body or due to various external factors. .
  • the food composition can effectively maintain joint and bone health by affecting the differentiation of osteoblasts and promoting bone regeneration.
  • the food composition can be used as a health functional food related to bone health improvement, growth promotion, and bone disease.
  • the health functional food refers to a food manufactured and processed using raw materials or ingredients that have useful functionality for the human body according to the Health Functional Food Act, and the functionality is to control nutrients for the structure and function of the human body or It may mean ingestion for the purpose of obtaining a useful effect for health purposes such as action.
  • the food composition may contain ordinary food additives, and the food additives are subject to the standards and standards for the relevant item according to the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. Whether it is appropriate or not can be determined.
  • the items described in the food additive code include, for example, ketones, glycine, potassium citrate, nicotinic acid, cinnamic acid, and other chemical compounds, dyestuffs, licorice extract, crystalline cellulose, high-volume pigments, natural additives such as guar gum, sodium L-glutamate preparations, and noodles.
  • Mixed preparations such as an added alkali agent, a preservative preparation, and a tar color preparation, are mentioned.
  • the food composition may be variously used in foods and beverages for enhancing immunity or improving bone disease, and for example, it may be used in various foods, beverages, gum, tea, vitamin complexes, health functional supplements, food additives, and the like. .
  • the health functional food may be manufactured and processed into any one formulation selected from the group consisting of tablets, granules, powders, capsules, liquid solutions, and pills for the purpose of enhancing immunity or improving bone disease.
  • a mixture of copper fruit extract, excipients, binders, disintegrants and other additives is granulated in a conventional manner, and then compression molded by putting a lubricant or the like, or directly compressing the mixture. It can be manufactured by molding.
  • the health functional food in the form of a tablet may contain a mating agent or the like, if necessary, and may be coated with a suitable coating agent if necessary.
  • hard capsules can be prepared by filling a conventional hard capsule with a mixture of additives such as copper fruit extract and excipients, granules thereof, or coated granules, and soft capsules are copper fruit extracts. And a mixture with an additive such as an excipient may be filled in a capsule base such as gelatin.
  • the soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
  • the ring-shaped health functional food can be prepared by molding a mixture of copper fruit extract, excipient, binder, and disintegrant by an appropriate method. Substances can also be used to create a pleasing feeling.
  • the granular health functional food may be prepared in a granular form of a mixture of copper fruit extract, excipients, binders, disintegrants, and the like by a suitable method, and may contain flavoring agents, flavoring agents, and the like, if necessary.
  • a pharmaceutical composition for preventing or treating bone diseases comprising a copper fruit extract as an active ingredient.
  • prevention refers to any action that reduces the frequency or severity of pathological symptoms. Prevention can be complete or partial. In this case, it may mean a phenomenon in which symptoms caused by inflammation in the individual decrease compared to the case where the composition is not used.
  • treatment refers to any action that clinically intervenes in order to change the natural process of a target or cell to be treated, and may be performed while a clinical pathology is in progress or to prevent it.
  • the desired therapeutic effect is to prevent the occurrence or recurrence of the disease, alleviate symptoms, reduce all direct or indirect pathological consequences of the disease, prevent metastasis, reduce the rate of disease progression, or It may include alleviating or temporarily alleviating the condition, or improving the prognosis.
  • the composition may be administered in the form of oral delivery or parenteral delivery.
  • the composition may be administered systemically or locally, and the administration may include oral administration and parenteral administration.
  • the composition may be formulated with a suitable amount of a pharmaceutically acceptable vehicle or carrier to provide an appropriate dosage form.
  • the composition may further include a carrier, an excipient, and a diluent used in the preparation of a pharmaceutical composition.
  • the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil, but are not limited thereto.
  • composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injectable solutions.
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injectable solutions.
  • Solid preparations for oral administration may include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient, such as starch, calcium carbonate, and sucrose, in the copper fruit extract and its fractions. , Lactose, or gelatin may be mixed and prepared. In addition, in addition to the excipients, lubricants such as magnesium stearate and talc may be used.
  • Liquid preparations for oral administration may include suspensions, liquid solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., may be used in addition to simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration may be sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories.
  • aqueous solutions non-aqueous solutions
  • suspensions emulsions
  • lyophilized formulations emulsions
  • suppositories emulsions
  • suppositories propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate
  • injectable ester such as ethyl oleate
  • witepsol macrogol, tween 61, cacao butter, laurin paper, and glycerogelatin may be used.
  • the pharmaceutical composition may be administered to a subject in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of disease, severity, drug activity, drug Sensitivity, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field.
  • the pharmaceutical composition may be administered as an individual therapeutic agent or administered in combination with another therapeutic agent, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is preferable to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all of the above factors, and this can be easily determined by a person skilled in the art.
  • the composition may be used for one or more materials selected from the group consisting of artificial bones, artificial joints, bone fixation materials, bone substitutes, bone repair materials, bone fillers, and bone graft materials.
  • the composition for promoting bone formation may be used for the prevention and treatment of bone disease or periodontal disease, and may be prepared in a form that is easy to be applied to artificial bone, bone fixation material, bone substitute, bone repair material, bone filler, or bone graft material. .
  • the bone graft material or bone substitute may be used to fill a space in bone tissue in a narrow way, and may be used in a broad sense to replace part of a bone or tooth. Therefore, the composition for promoting bone formation can be used in the form of putty, paste, moldable strips, blocks, chips, etc. using methods such as compression, compression, pressure contact, packing, compression, and hardening, and chemical additives are used. Thus, it may be formulated and used in the form of gels, granules, pastes, tablets, pellets, etc., and may also be used in powder form.
  • the obtained liquid extract was concentrated (20 brix) with a rotary vacuum concentrator, and then a copper fruit extract was obtained using a freeze dryer.
  • the yield of the extract obtained by powdering was 51.6% compared to the dried product.
  • the obtained liquid extract was concentrated (20 brix) with a rotary vacuum concentrator, and then a copper fruit extract was obtained using a freeze dryer.
  • the yield of the extract obtained by powdering was 53.5% compared to the dried product.
  • the cell line RAW264.7 macrophage cell was purchased and used from the American Type Culture Collection (ATCC, Manassas. USA).
  • DMEM Dulbecco's modified of Eagle's medium, Hyclone, USA
  • FBS Fetal Bovin Serum
  • penicillin/Streptoycin 100 units/mL penicillin/Streptoycin (Hyclone, USA) was used, 37 C. Incubated in an incubator (Thermo, Forma, Germany) in the presence of 5% CO 2.
  • Cell viability was measured by measuring the concentration of the produced formazan with a spectrophotometer using the change from Tetrazolium salt (WST-1) to formazan by mitochondrial dehydrogenase in living cells.
  • MTT assay was performed according to the protocol using Ez-cytox (Dozen, Korea).
  • Raw264.7 cells were dispensed into 96 wells at 5 ⁇ 10 3 cells/100 ⁇ L and incubated for 24 hours in a 37°C, 5% CO 2 incubator.
  • Toxicity evaluation based on cell viability for each sample was measured by repeating three times, and the mean value and standard deviation were calculated.
  • the copper fruit extract (Preparation Example 1), and the copper fruit ethanol extract (Preparation Example 2) showed no cytotoxicity in all concentrations (10, 100, 1000 ⁇ g/mL) range.
  • osteoblasts (MC3T3-E1) were dispensed into 96 wells at 5x10 3 cells/100 ⁇ L and stabilized for 24 hours.
  • Samples were treated by concentration and incubated in a CO 2 incubator for 48 hours. After incubation, MTT (EZ-cytox, Daillab) solution was treated and CO 2 was incubated for 2 hours, and then analyzed with a microplate reader (Epoch, Biotek) at 450 nm wavelength.
  • MTT EZ-cytox, Daillab
  • the osteoblast differentiation amount increased by 24% compared to the control at 100 ⁇ g/mL, and about 49% increased compared to the control at 1000 ⁇ g/mL.
  • the osteoblast differentiation amount increased by about 21% compared to the control at 100 ⁇ g/mL, and about 41% compared to the control at 1000 ⁇ g/mL.
  • ALP alkaline phosphatase
  • MC3T3-E1 (osteocyte) was dispensed into 48 wells at 5x10 3 cells/250 ⁇ L and stabilized for 24 hours.
  • Samples were treated by concentration and incubated in a CO 2 incubator for 7 days. After washing with PBS, lysis buffer was added to dissolve, and centrifuged at 12,000 rpm for 15 minutes.
  • the supernatant was collected by precipitating cell membrane components, and the ALP activity in the supernatant was quantified using an ALP assay kit.
  • the copper and hot water extract (Preparation Example 1) increased by 32% compared to the control at 100 ⁇ g/mL, and increased by 105% at 1000 ⁇ g/mL.
  • Protein concentration was normalized using bovine serum albumin (BSA). The lysate was separated by 30 ⁇ g 10% gel SDS-PAGE and transferred to the PVDF membrane for 120 V for 90 minutes.
  • BSA bovine serum albumin
  • Membrane blocking was performed for 1 hour in a TBS-T solution containing 5% skim milk.
  • the primary antibody (1:100 ⁇ 1000) was incubated at 4°C for one hour and then washed three times with TBS-T the next day.
  • HRP horse radish peroxidase
  • the copper and hot water extract (Preparation Example 1) increased by about 62% compared to the control at 100 ⁇ g/mL, and about 118% at 1000 ⁇ g/mL.
  • mice with a skull defect were treated with copper fruit extract, BMP-2 or a control group, and then micro-CT ( ⁇ CT) and histological analysis were performed.
  • ⁇ CT micro-CT
  • micro-CT micro-CT
  • the measurement method is a method for observing normal bone metabolism and uses a phenomenon in which a fluorescent factor is deposited on the bone through a chelate bond with calcium.
  • the administered fluorescent factor When a fluorescent factor is administered during the growth period in which bone formation is most active, the administered fluorescent factor most often deposits in the bone neoplasm under the bone growth plate to form a line. Was observed with a fluorescence microscope to measure the grown length.
  • the collected section was placed on a slide glass, dried, and the length between the growth plate and the line formed by the deposition of fluorescent factors in the bone tissue was measured using a fluorescence microscope to measure the degree of growth of the ilium of the rat.

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Abstract

La présente invention concerne un produit alimentaire et une composition pharmaceutique contenant un extrait de melon d'hiver en tant que principe actif pour augmenter la santé osseuse.
PCT/KR2020/014640 2019-11-15 2020-10-26 Composition contenant un extrait de melon d'hiver en tant que principe actif pour augmenter la santé osseuse WO2021096098A1 (fr)

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KR1020190146668A KR102312736B1 (ko) 2019-11-15 2019-11-15 동과 추출물을 유효성분으로 함유하는 뼈 건강 개선용 조성물

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102764336A (zh) * 2012-08-10 2012-11-07 冯德义 一种治疗骨外伤的中药
CN105213793A (zh) * 2015-10-15 2016-01-06 李涛 主治骨质疏松的中药组合物及制法
KR20170001491A (ko) * 2015-06-26 2017-01-04 이승현 동과를 이용한 음료의 제조방법

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102764336A (zh) * 2012-08-10 2012-11-07 冯德义 一种治疗骨外伤的中药
KR20170001491A (ko) * 2015-06-26 2017-01-04 이승현 동과를 이용한 음료의 제조방법
CN105213793A (zh) * 2015-10-15 2016-01-06 李涛 主治骨质疏松的中药组合物及制法

Non-Patent Citations (2)

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Title
LISA SHARMIN AKTER, ALAMGIR KABIR, AZMAL HOSSAIN, SELINA KHAN: "Nutritional value of some indigenous Cucurbitaceae oil seeds and physicochemical properties of their oils", JOURNAL OF CHEMICAL, BIOLOGICAL AND PHYSICAL SCIENCES, vol. 9, no. 1, 1 January 2019 (2019-01-01), XP055811947, DOI: 10.24214/jcbps.B.9.1.00109 *
UNE HEMANT DEVIDAS, DOSHI GAURAV MAHESH: "Carissa congesta Wight and Benincasa hispida (Thunb.) Cogn. as budding immunomodulatory agents", INDIAN J EXP BIOL., vol. 54, 1 October 2016 (2016-10-01), pages 650 - 658, XP055811944 *

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