KR20170014332A - Composition for preventing and treatment of osteoporosis - Google Patents
Composition for preventing and treatment of osteoporosis Download PDFInfo
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- KR20170014332A KR20170014332A KR1020150107475A KR20150107475A KR20170014332A KR 20170014332 A KR20170014332 A KR 20170014332A KR 1020150107475 A KR1020150107475 A KR 1020150107475A KR 20150107475 A KR20150107475 A KR 20150107475A KR 20170014332 A KR20170014332 A KR 20170014332A
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- Prior art keywords
- citron
- alcohol
- extract
- powder
- osteoporosis
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical compound O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
Abstract
The present invention relates to a pharmaceutical composition and a health functional food for preventing or treating osteoporosis containing an alcohol extract of citron as an active ingredient. The present invention also relates to a method for extracting citrus algae which is optimized for preventing and treating osteoporosis without destroying the active ingredients of osteoporosis prevention and treatment efficacy as much as possible.
Description
The present invention relates to a pharmaceutical composition for preventing or treating osteoporosis.
Osteoporosis is a disease caused by collapse of the balance between osteoblast and osteoclast, and bone resorption is higher than osteogenesis. In the onset of osteoporosis, the lime of the bone tissue is reduced, and the density of the bone becomes thinner, thereby widening the bone marrow. As the condition progresses, the bones become weaker, so that even a small impact is liable to fracture. It is known that osteoporosis is caused by aging, lack of exercise, low body weight, smoking, low calcium diet, menopause, and ovarian resection.
Most osteoporosis medicines currently on the market are estrogenic substances, which cause side effects such as cancer, gallstones and thrombosis when administered over a long period of time. Osteoporosis is a disease that can not be treated only by short-term administration of a drug, and long-term administration of the drug is indispensable. Therefore, it is necessary to develop a new drug having a drug efficacy sufficient to replace estrogen without the side effects mentioned above even when the drug is administered for a long time.
Most conventional osteoporosis medicines focus on the regulation of the imbalance between osteoclasts and osteoblasts. However, it is known that osteoporosis is greatly affected by bone marrow-derived adipocytes as well as bone-related cells, and prevention and treatment of osteoporosis by inhibiting adipocyte formation or developing drugs capable of converting existing adipocytes into osteoblasts It is attracting attention as a new goal. This is based on the fact that osteoblasts and adipocytes have the same precursors and that the differentiation of osteoblast cells from mesenchymal stem cells is reduced and the differentiation into adipocytes is increased as the aging progresses.
On the other hand, citron is a kind of citrus produced in Korea, China, Japan and Northeast Asia. The Korean is the most fragrant and the skin is thick. The main production areas in Korea are Goheung, Jeolla, Jeollanamdo, etc.
Vitamin C is the main ingredient of citron, which is 3 times more than lemon. It is good for cold and skin beauty, and contains many organic acids to prevent aging and fatigue. In addition, vitamin B, carbohydrates, proteins and other citrus fruits, more than the capillaries to protect the flavonoids that contain the blood vessels and block the airflow obstruction. In addition, drainage and excretion work out the waste that is accumulated in the body is sent out.
Regarding the efficacy of such citron, Korean Patent No. 854,403 discloses a process for producing citron extract, which comprises extracting citron seeds with ethanol and drying the citron seed extract, which is a dry powder obtained by ethanol extraction, Discloses a food exhibiting an obesity-suppressing effect comprising a composition wherein the leaf extract powder is comprised between 3: 7 and 6: 4 (w / w). Korean Patent No. 1,492,470 discloses a method for producing yuza seed oil having enhanced atherosclerotic potential and Korean Patent No. 1,383,145 discloses a composition for prevention and treatment of benign prostatic hyperplasia including citron extract. .
However, the efficacy of citrus juice for osteoporosis has not yet been elucidated.
It is an object of the present invention to provide a pharmaceutical composition and a health functional food which are excellent in osteoporosis prevention and treatment efficacy and have little side effects even when taken for a long time. In particular, we have developed a technique that can reduce differentiation from mesenchymal stem cells into adipocytes and promote osteoblast differentiation and activity.
The present invention relates to a pharmaceutical composition for preventing or treating osteoporosis, which contains an alcohol extract of citron as an active ingredient.
The composition may be one that promotes osteoblast differentiation and activity.
The alcohol may preferably be ethanol.
The extract can be obtained by mixing 0.1 to 20 g of citron peel powder with 100 ml of alcohol and extracting at a temperature of 20 to 60 ° C for 12 to 36 hours.
The composition may be formulated in the form of powders, granules, tablets, hard capsules, soft capsules or injections.
The composition may further comprise one or more pharmaceutically acceptable carriers selected from the group consisting of diluents, excipients, disintegrants, binders and glidants.
In another aspect, the present invention relates to a health functional food for preventing or improving osteoporosis containing an alcohol extract of citron as an active ingredient.
The composition may be one that promotes osteoblast differentiation and activity.
The alcohol may preferably be ethanol.
The extract can be obtained by mixing 0.1 to 20 g of citron peel powder with 100 ml of alcohol and extracting at a temperature of 20 to 60 ° C for 12 to 36 hours.
In another aspect, the present invention provides a process for preparing a fermented beverage comprising: (a) lyophilizing the peel of citron to obtain a powder, and then mixing 0.1 to 20 g of citron powder per 100 ml of alcohol; (b) agitating the mixture at a temperature of 20 to 60 DEG C for 12 to 36 hours to elute the active ingredient; And (c) removing the solid content from the extraction solution, concentrating only the supernatant, and concentrating the extract.
The average particle size of the citron powder mixed in the alcohol in the step (a) is preferably 0.1 to 0.5 占 퐉.
The extraction temperature in step (b) is preferably 20 to 30 ° C.
The step (c) may further comprise lyophilizing the concentrated liquid to obtain a powder.
The composition may be one that promotes osteoblast differentiation and activity.
The alcohol may preferably be ethanol.
The pharmaceutical composition and the health functional food containing the citrus peel extract of the present invention as an active ingredient are useful for reducing osteoblastic differentiation from mesenchymal stem cells and promoting osteoblast differentiation and activity, It has the advantage of less side effects even when taken.
Also, the present invention relates to a method for extracting citron citron extracts, which is excellent in prevention and treatment of osteoporosis without destroying the active ingredients of osteoporosis prevention and treatment efficacy as much as possible.
Fig. 1 shows experimental results of Example 1 in which the effect of the citron extract of the present invention on osteoblast differentiation activity was evaluated.
FIG. 2 and FIG. 3 show the results of the experiment according to Example 2, which evaluated the effect of the citron extract of the present invention on bone formation of osteoporosis-induced rats.
FIG. 4 shows the results of the experiment according to Example 3 in which the citron extract of the present invention was evaluated for the influence of osteoporosis-induced rats on lipid formation.
Hereinafter, the present invention will be described in detail.
Pharmaceutical composition for preventing or treating osteoporosis
In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating osteoporosis containing an alcohol extract of citron as an active ingredient.
The alcoholic extract of citron reduces the differentiation from mesenchymal stem cells into adipocytes and promotes osteoblast differentiation and activity, and thus can be usefully used as a pharmaceutical composition for the prevention or treatment of osteoporosis.
The solvent used for the extraction of the alcoholic extract of citron may be ethanol. Specifically, 0.1 to 20 g of citrus peel powder is mixed with 100 ml of alcohol, and extraction is carried out at a temperature of 20 to 60 ° C for 12 to 36 hours . ≪ / RTI > A preferred method for producing the alcoholic extract of citrus peel used in the present invention will be described in more detail below.
As used herein, the term osteoporosis refers to a state in which the amount of bone is reduced and the strength of the bone is weakened due to a qualitative change, and the prevention, improvement and treatment of osteoporosis includes all kinds of diseases caused by decreased bone density and bone loss .
The pharmaceutical composition according to the present invention can be administered orally or parenterally at the time of clinical administration and can be used in the form of a general pharmaceutical preparation. Each can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppository sterilized injection solutions, pre-filled injection solutions or lyophilized form But is not limited thereto.
In the case of formulation, it may be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.
Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, gelatin, . In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. may be included in addition to water and liquid paraffin which are simple diluents commonly used have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
The composition of the present invention may contain at least one active ingredient which exhibits the same or similar function in addition to the above extract.
The preferred dosage of the pharmaceutical composition of the present invention can be appropriately selected depending on the condition and the weight of the patient, the degree of symptoms, the drug form, the administration route and the period. It is preferable for the composition of the present invention to allow the active ingredient to be administered at 0.2 mg / kg to 200 mg / kg per day for optimal efficacy. The administration may be carried out once a day or divided into several doses, but is not limited thereto.
Health functional food for preventing or improving osteoporosis
In another aspect, the present invention relates to a health functional food for preventing or improving osteoporosis containing an alcohol extract of citron as an active ingredient.
The alcoholic extract of citron reduces the differentiation from mesenchymal stem cells into adipocytes and promotes osteoblast differentiation and activity, and thus can be usefully used as a health functional food for preventing or improving osteoporosis.
The solvent used for the extraction of the alcoholic extract of citron may be ethanol. Specifically, 0.1 to 20 g of citrus peel powder is mixed with 100 ml of alcohol, and extraction is carried out at a temperature of 20 to 60 ° C for 12 to 36 hours . ≪ / RTI > A preferred method for producing the alcoholic extract of citrus peel used in the present invention will be described in more detail below.
The health functional food of the present invention can be manufactured in various forms such as, but not limited to, various drinks, gum, tea, confectionery, vitamin complex, health supplement and the like.
In addition, the health functional food of the present invention includes a case where it is added to a health food for the purpose of improving osteoporosis, and there is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.
The preferred intake amount of the health functional food of the present invention varies depending on the condition and body weight of the recipient, the degree of symptoms, the type of food, and the period of consumption, and can be appropriately selected. It is preferable for the health functional food of the present invention that the active ingredient is ingested at 0.2 mg / kg to 200 mg / kg per day for optimal effect.
Process for the production of citron extract for the prevention or treatment of osteoporosis
In another aspect, the present invention provides a process for preparing a fermented beverage comprising: (a) lyophilizing the peel of citron to obtain a powder, and then mixing 0.1 to 20 g of citron powder per 100 ml of alcohol; (b) agitating the mixture at a temperature of 20 to 60 DEG C for 12 to 36 hours to elute the active ingredient; And (c) removing the solid content from the extraction solution, concentrating only the supernatant, and concentrating the extract. The process for producing the citron extract according to the present invention will be described step by step.
First, (a) the peel of citron is lyophilized to obtain a powder, and 0.1 to 20 g of citron powder per 100 ml of alcohol are mixed.
The citron powder is obtained by lyophilization of citron peel. The average particle size of citron powder mixed with alcohol is preferably 0.1 to 0.5 mu m, more preferably 0.25 mu m or less. When citron powder having an average particle size of 0.1 to 0.5 탆 is used, there is an advantage that the effective ingredient can be effectively extracted even at a low temperature for a short time while minimizing destruction of the effective ingredient for prevention of osteoporosis. On the other hand, in order to control the particle size of the obtained citron powder by lyophilization, the powder may be pulverized by a pulverizer or the citron powder may be passed through a sieve to select only particles of a desired size.
Alcohols used as extraction solvents include, but are not limited to, lower alcohols of 1 to 4 or polyhydric alcohols, or mixtures thereof. Preferably the alcohol is ethanol. When ethanol is used as the extraction solvent, it can extract the active ingredient more effectively, reduce the complexity of the extracted compound, have low cost, low toxicity, and easy to remove.
The ratio of the extraction solvent to the citron powder is preferably 0.1 to 20 g of citron powder per 100 ml of alcohol, more preferably 5 to 15 g, particularly preferably about 10 g per citron of 100 ml of alcohol.
Next, (b) the active ingredient for osteoporosis treatment is eluted from the citron while stirring the mixture of the extraction solvent and the citron powder at a temperature of 20 to 60 DEG C for 12 to 36 hours. In this case, the extraction temperature is more preferably 20 to 30 ° C, and most preferably, it is extracted at about room temperature of about 25 ° C. If the extraction temperature is higher than the above range, the active ingredient may be destroyed. If the extraction temperature is low, the extraction time becomes longer and the economical efficiency is lowered. The extraction time may vary depending on the extraction temperature, but most preferably about 24 hours.
When the extraction is completed, (c) the solid content is removed from the extraction solution, and only the supernatant is collected and concentrated. Separation of the solids and the supernatant may be carried out, for example, using a filter paper, or by centrifugation. In addition, (d) lyophilization of the concentrate of step (c) may include the step of obtaining a powder.
Hereinafter, the process for producing the citrus juice extract of the present invention, its pharmaceutical composition and its application as a health functional food will be described in more detail with reference to the following Preparation Examples and Preparation Examples. However, the following Preparation Examples and Preparation Examples are for the purpose of specifying the content of the present invention, but the present invention is not limited by Examples.
< Manufacturing example >
Manufacturing example 1. Preparation of citron extract
Citrus peel was dried and then pulverized using a crusher. At this time, the average particle size of the citron powder is 0.1 to 0.5 占 퐉. To 100 g of the citron powder was added 500 ml of an aqueous 70 vol.% Ethanol solution. The mixture was extracted with stirring at 25 DEG C for 24 hours, and then the solid content was removed at 8,000 DEG C for 30 minutes using a centrifuge (Beckman, USA). The centrifuged supernatant was collected, concentrated under reduced pressure, and lyophilized to give a powder.
< Formulation example >
Formulation example One: Sanje Produce
Citron powder (Preparation Example 1) - 300 mg
Lactose ------------------------------ 100 mg
Talc ------------------------------ 10 mg
The above components are mixed and filled in airtight bags to prepare powders.
Formulation example 2: Preparation of tablets
Citron powder (Preparation Example 1) - 50 mg
Corn starch ------------------------------ 100 mg
Lactose ------------------------------ 100 mg
Magnesium stearate ----------------------------- 2 mg
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
Formulation example 3: Preparation of capsules
Citron powder (Preparation Example 1) - 50 mg
* Corn starch ------------------------------ 100 mg
Lactose ------------------------------ 100 mg
Magnesium stearate ----------------------------- 2 mg
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
Formulation example 4: Preparation of injection
Citron powder (Preparation Example 1) - 50 mg
Sterile sterilized distilled water for injection ---------------------------
pH adjusting agent -----------------------------
(2 ml) per 1 ampoule according to the usual injection preparation method.
Formulation example 5: Liquid Produce
Citron powder (Preparation Example 1) - 100 mg
Isomer ------------------------------ 10 g
Mannitol ------------------------------ 5 g
Purified water ------------------------------
Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.
Formulation example 6: Of health food Produce
Citron powder (Preparation Example 1) - 1000 mg
Vitamin mixture ------------------------------
Vitamin A Acetate -------------------------- 70 g
Vitamin E ------------------------------ 1.0 mg
Vitamin B1 ------------------------------ 0.13 mg
Vitamin B2 ------------------------------- 0.15 mg
Vitamin B6 ------------------------------ 0.5 mg
Vitamin B12 ------------------------------ 0.2 g
Vitamin C ------------------------------ 10 mg
Biotin ------------------------------- 10 μg
Nicotinic amide ------------------------------ 1.7 mg
Folic acid ---------------------------------- 50 μg
Calcium pantothenate ------------------------------ 0.5 mg
Inorganic mixture -------------------------------
Ferrous sulfate ------------------------------ 1.75 mg
Zinc oxide ------------------------------ 0.82 mg
Magnesium carbonate ------------------------------ 25.3 mg
Potassium phosphate monohydrate 15 mg
Secondary phosphate knife ------------------------ 55 mg
Potassium citrate -------------------------- 90 mg
Calcium carbonate -------------------------------- 100 mg
Magnesium Chloride ------------------------------- 24.8 mg
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
Formulation example 7: Manufacture of health drinks
Citron powder (Preparation Example 1) - 1000 mg
Citric acid ------------------------------ 1000 mg
oligosaccharide ---------------------------- 100 g
Plum concentrate ----------------------------- 2 g
Taurine ------------------------------ 1 g
Purified water was added to the whole to 900 ml
The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, ≪ / RTI > Although the composition ratio is relatively mixed with a component suitable for a favorite beverage as a preferred embodiment, the blending ratio may be arbitrarily varied depending on the regional or national preference such as the demand class, the demanding country, and the usability.
Hereinafter, the effects of the alcohol extract of citron according to the present invention on osteoporosis treatment and prevention activity will be described in more detail with reference to the following examples.
< Example >
Example 1. Measurement of effect on osteoblast differentiation activity
(1) Survival rate
To measure the effect of citron extract on the survival of osteoblasts, citron extracts of 50 μg / ml, 100 μg / ml, 200 μg / ml and 400 μg / ml were added to mouse-derived MC3T3-E1 cells And the survival rate was measured after 48 hours. As a result, the cell growth rate was increased in all the groups to which citron extract was added, and the cell growth rate was remarkably increased in the group to which 100 μg / ml or more citron extract was added (see FIG. 1A).
(2) ALP activity effect
The effect of citron extract on osteoblastic activity was investigated by measuring ALP (alkaline phosphate) activity. First, to induce osteoblast differentiation Cells were seeded in a 24-well plate at 5 × 10 4 cells per well and cultured for 2 days. Then, the cells were cultured in a differentiation induction medium (50 μg / mL L-ascorbic acid and 10 mM β-glycerophosphate). When the medium was changed every 3 days, the differentiation inducing agent and the citron extract were treated at the same concentration.
After induction of differentiation, the cells were washed twice with PBS, and lysed by adding 80 μl / well of 0.2% Triton-X-100 lysis buffer (kit product). After stirring for 10 minutes at 4 ° C, the supernatant was separated by centrifugation at 2500 × g for 10 minutes.
20 μl of supernatant was added to a 96-well plate and 20 μl of pNPP solution (kit product) was added to the supernatant. After incubation at 37 ° C for 30 min, the reaction was stopped by adding 15 μl of stop solution. The absorbance was measured at 405 nm and the amount converted to p-nitrophenol by ALP enzyme was calculated. Since ALP activity may be affected by the number of cells, the amount of total protein was measured to adjust the ALP activity.
As a result, when 50 μg / m, 100 μg / ml and 200 μg / ml of citron extract were added to MC3T3-E1 cells, the ALP activity was increased in all concentrations in a concentration-dependent manner, ml, it was confirmed that the ALP activity was superior to that of the positive control (treated with 100 nM estrogen) (see Fig. 1B) . ALP is a biomarker expressed in the differentiation of osteoblast, and it was confirmed that citron extract promotes osteoblast differentiation.
(3) Calcification Formability
Differentiation-induced cells were fixed with 4% formalin at room temperature for 10-30 minutes or overnight at 4 ° C, and then washed 2-3 times with distilled water. A solution of Alizarin Red (0.4 g / 20 mL, pH 4.6) was added to each well and stained for 5 minutes. After washing several times with distilled water, 1 mL of 10% acetylchloride dissolved in 1 mM sodium phosphate was added and shaken in a shaker for 20 minutes to dissolve the Alizarin Red staining. The absorbance was measured at 562 nm.
The results showed that Alizarin staining and absorbance were increased in proportion to the concentration of citron extract. Since calcitization ability is a biomarker important for osteoblast differentiation, Alizarin is stained in the matrix of mineralized cells, and thus the calcified amount and the degree of staining are in proportion to each other. As a result, it is confirmed that osteoblast is calcified in the extract of citron of the present invention (See Figs. 1C and 1D).
Example 2. Measure the effect on osteoporosis
In order to investigate the effect of citron extract on osteogenesis of osteoporosis-induced rats, 2-month-old female rats were divided into normal group (SHAM), ovariectomized group (OVX), female hormone (17-beta-estradiol ), Ovariectomized group (OVX + Es) injected with ovariectomized group (OVX + Es) injected with 5% / kg d 1 et / Were prepared, and the following experiment was carried out.
(One) Weight, intake and uterine weight change in osteoporosis-induced rats
The changes in body weight, the intake and the intake efficiency, the liver weight, the fat weight and the uterine weight of the four groups of rats were measured after 10 weeks, and the results are shown in Table 1.
(FER,%)
2) OVX: ovariectomized group
3) OVX + ES: ovariectomized group injected with female hormone (17-beta-estradiol)
4) OVX + citron: ovariectomized group injected with citron extract
# p < 0.05, ### p < 0.001 OVX vs.. SHAM; * p < 0.05, * * p < 0.01, *** p < 0.001, OVX + Es, OVX + OVX.
As shown in Table 1, in the group injected with citron extract (OVX + citron) according to the present invention, an increase in body weight was observed compared with that in the ovariectomized group (OVX). In addition, the weight of uterus decreased in ovariectomized group was significantly restored in the group treated with citron extract.
Therefore, it was confirmed that the citron extract according to the present invention can be effectively used for prevention or treatment of osteoporosis by reducing the body weight of osteoporosis-induced rats and restoring the smaller uterus.
(2) ALP changes in osteoporosis-induced rats
ALP and osteocalcin are used as bone formation markers. Total plasma ALP, bone specific ALP, and osteocalcin concentrations were measured for the four groups of rats. The results showed that the total blood ALP and bone specific ALP levels increased significantly in the ovariectomized group (OVX) and the ovariectomized group (ovariectomized group) OVX + Es) (Fig. 2A and Fig. 2B) .
From these experimental results, it was confirmed that citron extract can be useful for preventing or treating osteoporosis by increasing bone formation.
(3) microCT Changes in bone mineral density and bone microstructure through measurement
To investigate the effect of the citron extract according to the present invention on the recovery of bone, microcontrast of the bones was examined by using a tibia on the rats of the four groups and bone mineral density (bone mineral (BMD), bone volume / total volume (BV / TV), trabecular space (Tb.Sp) and trabecular number (Tb.N) were measured.
As a result of the experiment, it was confirmed that the microstructure of the bony bone shown in the ovariectomized group (OVX) was dense in the group injected with citron extract (OVX + citron) ( see FIG. 3A), and the lowered BMD (See FIG. 3B) . (BV / TV) (Fig. 3C) and the interval between the bone elements (Tb.Sp) was significantly higher than that of the ovariectomized group (OVX + (See Figure 3D), and the number of bone trabeculae (Tb.N) increased (see Figure 3D).
Therefore, the citron extract according to the present invention can restore osteoporosis by increasing the bone mineral density and the microstructure of the bones weakened by osteoporosis.
Example 3. Measurement of the effect on lipid formation
Total-cholesterol (TG), total-cholesterol (HDL-C), and total cholesterol were measured for the four groups of rats prepared in Example 2 to examine the effect of citron extract on the lipidogenesis of osteoporosis-induced rats. LDL-C was measured. The results showed that TG, total-C, and LDL-C values were decreased in the group injected with citron extract (OVX + citron) compared to the ovariectomized group (OVX) (see FIGS. 4A, 4B, C was increased (see Fig. 4C) . That is, it was confirmed that the citron extract according to the present invention has an effect on osteoporosis by reducing blood lipid.
Claims (16)
(b) agitating the mixture at a temperature of 20 to 60 DEG C for 12 to 36 hours to elute the active ingredient; And
(c) removing the solid content from the extraction solution, concentrating only the supernatant, and concentrating the concentrate, thereby producing an oat extract for preventing or treating osteoporosis.
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