KR101577732B1 - Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease - Google Patents
Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease Download PDFInfo
- Publication number
- KR101577732B1 KR101577732B1 KR1020130082407A KR20130082407A KR101577732B1 KR 101577732 B1 KR101577732 B1 KR 101577732B1 KR 1020130082407 A KR1020130082407 A KR 1020130082407A KR 20130082407 A KR20130082407 A KR 20130082407A KR 101577732 B1 KR101577732 B1 KR 101577732B1
- Authority
- KR
- South Korea
- Prior art keywords
- disease
- fermented product
- menopausal
- fermented
- yellowish white
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- 239000004480 active ingredient Substances 0.000 title claims abstract description 11
- 230000002265 prevention Effects 0.000 title claims abstract description 9
- 208000029725 Metabolic bone disease Diseases 0.000 title abstract description 31
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 title abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 15
- 201000010099 disease Diseases 0.000 title abstract description 13
- 241000972672 Phellodendron Species 0.000 title description 2
- 208000017657 Menopausal disease Diseases 0.000 claims abstract description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 16
- 235000013376 functional food Nutrition 0.000 claims abstract description 14
- 230000036541 health Effects 0.000 claims abstract description 14
- 206010046764 Uterine atrophy Diseases 0.000 claims abstract description 12
- 231100001042 uterine atrophy Toxicity 0.000 claims abstract description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 64
- 239000004310 lactic acid Substances 0.000 claims description 32
- 235000014655 lactic acid Nutrition 0.000 claims description 32
- 239000000284 extract Substances 0.000 claims description 31
- 241000894006 Bacteria Species 0.000 claims description 28
- 244000199866 Lactobacillus casei Species 0.000 claims description 11
- 235000013958 Lactobacillus casei Nutrition 0.000 claims description 11
- 229940017800 lactobacillus casei Drugs 0.000 claims description 11
- 244000005700 microbiome Species 0.000 claims description 8
- 229940011871 estrogen Drugs 0.000 claims description 6
- 239000000262 estrogen Substances 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 5
- 208000004611 Abdominal Obesity Diseases 0.000 claims description 4
- 206010065941 Central obesity Diseases 0.000 claims description 4
- 241000194036 Lactococcus Species 0.000 claims description 4
- 241000194017 Streptococcus Species 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 241000186610 Lactobacillus sp. Species 0.000 claims description 3
- 241000131482 Bifidobacterium sp. Species 0.000 claims description 2
- 241000178948 Lactococcus sp. Species 0.000 claims description 2
- 241001627205 Leuconostoc sp. Species 0.000 claims description 2
- 241000604136 Pediococcus sp. Species 0.000 claims description 2
- 241000194022 Streptococcus sp. Species 0.000 claims description 2
- 230000002611 ovarian Effects 0.000 claims description 2
- 240000001046 Lactobacillus acidophilus Species 0.000 claims 3
- 230000003247 decreasing effect Effects 0.000 claims 2
- 210000002997 osteoclast Anatomy 0.000 abstract description 35
- 210000000988 bone and bone Anatomy 0.000 abstract description 31
- 230000004069 differentiation Effects 0.000 abstract description 14
- 210000000579 abdominal fat Anatomy 0.000 abstract description 11
- 239000000047 product Substances 0.000 description 57
- 238000000855 fermentation Methods 0.000 description 24
- 230000004151 fermentation Effects 0.000 description 24
- 230000000694 effects Effects 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 16
- 241000186660 Lactobacillus Species 0.000 description 12
- 229940039696 lactobacillus Drugs 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 10
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 10
- 239000003814 drug Substances 0.000 description 9
- 230000007423 decrease Effects 0.000 description 8
- 235000013305 food Nutrition 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 208000001132 Osteoporosis Diseases 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 210000000963 osteoblast Anatomy 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000011164 ossification Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 244000144725 Amygdalus communis Species 0.000 description 4
- 235000011437 Amygdalus communis Nutrition 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 235000020224 almond Nutrition 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000000689 upper leg Anatomy 0.000 description 4
- 238000001061 Dunnett's test Methods 0.000 description 3
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 210000004979 bone marrow derived macrophage Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000010603 microCT Methods 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 238000009806 oophorectomy Methods 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 241000186000 Bifidobacterium Species 0.000 description 2
- 206010068975 Bone atrophy Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 206010016825 Flushing Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000037147 Hypercalcaemia Diseases 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010027304 Menopausal symptoms Diseases 0.000 description 2
- 206010030247 Oestrogen deficiency Diseases 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000003076 Osteolysis Diseases 0.000 description 2
- 206010049088 Osteopenia Diseases 0.000 description 2
- 102000008108 Osteoprotegerin Human genes 0.000 description 2
- 108010035042 Osteoprotegerin Proteins 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- 241000192001 Pediococcus Species 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 201000010103 fibrous dysplasia Diseases 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 230000000148 hypercalcaemia Effects 0.000 description 2
- 208000030915 hypercalcemia disease Diseases 0.000 description 2
- 230000037315 hyperhidrosis Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000009245 menopause Effects 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 2
- -1 olive oil Chemical compound 0.000 description 2
- 230000000010 osteolytic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000036299 sexual function Effects 0.000 description 2
- 230000009759 skin aging Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 238000004260 weight control Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- SARKXLKWFKNUMR-UHFFFAOYSA-N 4-benzamido-5-chloro-2-methylbenzenediazonium;chloride Chemical compound [Cl-].C1=C([N+]#N)C(C)=CC(NC(=O)C=2C=CC=CC=2)=C1Cl SARKXLKWFKNUMR-UHFFFAOYSA-N 0.000 description 1
- 241000227585 Alstonia constricta Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000555682 Forsythia x intermedia Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 241000192132 Leuconostoc Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 244000028344 Primula vulgaris Species 0.000 description 1
- 235000016311 Primula vulgaris Nutrition 0.000 description 1
- 240000006831 Rubus chamaemorus Species 0.000 description 1
- 235000016554 Rubus chamaemorus Nutrition 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 244000250129 Trigonella foenum graecum Species 0.000 description 1
- 235000001484 Trigonella foenum graecum Nutrition 0.000 description 1
- 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 description 1
- 101710178436 Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 235000012206 bottled water Nutrition 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012907 medicinal substance Substances 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 208000015124 ovarian disease Diseases 0.000 description 1
- 201000004535 ovarian dysfunction Diseases 0.000 description 1
- 231100000543 ovarian dysfunction Toxicity 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000001019 trigonella foenum-graecum Nutrition 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 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)
- A61K36/756—Phellodendron, e.g. corktree
-
- 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
- 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
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
-
- 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
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
본 발명은 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물, 상기 발효물을 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 개선용 건강기능식품 및 상기 발효물을 이용한 개체의 대사성 골질환 또는 갱년기 질환을 예방 또는 치료하는 방법에 관한 것이다.
본 발명에 따른 황백 발효물은 파골세포 분화를 억제하고, 골량을 증가시키며, 복부지방을 감소시키고, 자궁위축을 저해하는 효과를 나타내므로, 약학적 조성물 또는 건강기능식품의 형태로 제조되어 대사성 골질환 또는 갱년기 질환의 예방 또는 치료에 널리 활용될 수 있을 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of metabolic bone disease or menopausal disease which comprises a yellowish white fermented product as an active ingredient, a health functional food for preventing or ameliorating metabolic bone disease or menopausal disease, And a method for preventing or treating metabolic bone disease or menopausal disease of an individual using water.
The fermented product according to the present invention inhibits osteoclast differentiation, increases bone mass, reduces abdominal fat, and inhibits uterine atrophy. Thus, the fermented product is produced in the form of a pharmaceutical composition or a health functional food, Diseases or menopausal diseases.
Description
본 발명은 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물, 상기 발효물을 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 개선용 건강기능식품 및 상기 발효물을 이용한 개체의 대사성 골질환 또는 갱년기 질환을 예방 또는 치료하는 방법에 관한 것이다.
The present invention relates to a pharmaceutical composition for the prevention or treatment of metabolic bone disease or menopausal disease which comprises a yellowish white fermented product as an active ingredient, a health functional food for preventing or ameliorating metabolic bone disease or menopausal disease, And a method for preventing or treating metabolic bone disease or menopausal disease of an individual using water.
대사성 골질환은 신체 내에서 뼈를 생성하는 역할을 하는 조골세포 (osteoblast)와 뼈를 파괴하는 역할을 하는 파골세포(osteoclast) 간의 활성에 조화가 깨어지게 되면서 초래된다. 파골세포(osteoclast)는 뼈가 성장하는 과정에서 불필요하게 된 뼈조직을 파괴 또는 흡수하는 대형의 다핵세포이다. 성숙된 파골세포는 다핵세포이며 조혈모세포에서 기원된다. 중간엽 간세포에서 분화된 조골세포는 약 34개월간 생존하여 활성화된 파골세포가 낡은 뼈를 분해시킨 자리에서 새로운 뼈를 만든다. 수많은 조골세포가 골기질을 만들고 점차 기질이 무기질화 되면서 골형성이 마무리된다. 이후 조골세포의 약 70% 이상은 사멸되고 일부는 골세포(osteocyte) 및 골표면세포(bone lining cell)로 분화되어 생존한다. 뼈의 양은 파골세포와 조골세포의 균형에 의해 유지되므로 파골세포에 대해 중요한 역할을 하는 분자들을 표적으로 한 치료제 개발이 중요하다. 즉, 뼈를 흡수하는 파골세포의 활성이 증가하게 되면, 뼈의 분해가 촉진, 뼈가 얇아지고 쉽게 부러지는 골다공증과 같은 질병이 일어나게 되므로, 파골세포의 활성을 조절할 수 있는 인자들이 골 질환의 치료제로서 연구되고 있다.Metabolic bone disease is caused by the breakdown of the activity between osteoblasts, which play a role in bone formation in the body, and osteoclasts, which play a role in bone destruction. Osteoclast is a large polynuclear cell that destroys or absorbs bone tissue that has become unnecessary in the process of bone growth. The mature osteoclasts are polynuclear cells and originate from hematopoietic stem cells. The osteoblasts differentiated from the mesenchymal stem cells survive for about 34 months, and the activated osteoclasts break down the old bone, creating a new bone. A number of osteoblasts produce bone matrix and gradually become mineralized to complete bone formation. Approximately 70% of osteoblast cells are killed and some osteocytes and bone lining cells survive. Since the amount of bone is maintained by the balance between osteoclasts and osteoblasts, it is important to develop therapeutic agents that target molecules that play an important role in osteoclasts. In other words, as the activity of osteoclast-absorbing osteoclasts increases, diseases such as osteoporosis that is easily broken and bone thinning are promoted, factors that can control the activity of osteoclasts are treated as a treatment for bone diseases .
예컨대, 골감소증(osteopenia)은 골다공증의 전단계를 지칭하며 발생원인은 과도한 파골세포의 흡수(resorption) 및 형성에 기인한다고 알려져 있다. 류마티스에서 나타나는 골위축증(bone atrophy) 또한 과도한 파골세포의 흡수와 관련이 있다. 섬유성골이형성증(fibrous dysplasia)은 파골세포작용이 활발하여 나타난다. 파제트병(Paget disease)과 고칼슘혈증(hypercalcemia)은 파골세포 기능 억제를 통한 치료제가 이용되고 있다. 과도한 파골세포의 생성 및/또는 활성을 억제하면 뼈의 종양성 파괴(neoplastic bone destruction)를 억제할 수 있으며, 골용해(osteolysis)와 골관절염(osteoarthritis)은 파골세포의 흡수 증가 또는 파골세포의 분화 증가에 의해 발생한다.For example, osteopenia refers to the pre-stage of osteoporosis and is believed to be caused by excessive osteoclast resorption and formation. Bone atrophy in rheumatism is also associated with excessive osteoclast resorption. Fibrous dysplasia is manifested by osteoclastic activity. Paget disease and hypercalcemia have been used for treating osteoclast function. Inhibition of excessive bone cell production and / or activity may inhibit neoplastic bone destruction, and osteolysis and osteoarthritis may increase osteoclast uptake or osteoclast differentiation Lt; / RTI >
한편, 뼈로 들어온 암세포들은 뼈 주위의 미세환경에서 증식하여 파골세포나 조골세포 활성을 자극함으로써 골용해성 골전이로 진행될지 골조성 골전이로 진행될지를 결정하는 것으로 알려져 있다. 혈관을 따라 돌다가 뼈에 정착한 암 세포들은 PTHrP(parathyroid hormonerelatedprotein), 인터루킨(interleukin;IL)-1, IL-6, IL-8 그리고 IL-11와 같은 골용해인자(osteolytic factors)를 분비한다. 분비된 인자들은 조골세포에서 OPG(osteoprotegerin)의 발현을 줄이고 RANKL(receptor activator of NF-kB ligand)의 발현을 증가시킨다. 증가된 RANKL은 파골 전구 세포의 RANK와 결합하여 많은 수의 파골 전구 세포를 성숙화 시키고 결국에는 과다한 골 흡수에 의한 골 파괴를 야기시킨다.On the other hand, cancer cells entering the bone are known to proliferate in the microenvironment around the bone to stimulate osteoclast or osteoclast activity, thereby determining whether osteolytic bone formation proceeds to bone formation bone formation. Cancer cells that line the blood vessels and settle in the bone secrete osteolytic factors such as parathyroid hormone protein (PTHrP), interleukin (IL) -1, IL-6, IL-8 and IL-11 . Secreted factors reduce the expression of OPG (osteoprotegerin) in osteoblasts and increase the expression of RANKL (receptor activator of NF-kB ligand). Increased RANKL binds to RANK of osteoclast precursor cells to mature a large number of osteoclast precursor cells and eventually causes bone destruction due to excessive bone resorption.
또한, 갱년기 질환은 갱년기 즉, 50세를 전후하여 여성 성기능을 유지할 뿐만 아니라 혈액순환, 체중조절, 뼈관리를 돕는 등의 다양한 기능을 하는 여성호르몬인 에스트로겐의 분비가 저하되면서 발병하는 질환으로 갱년기가 아니더라도 난소 절제, 난소 기능저하 등 다른 원인에 의한 에스트로겐 결핍 환자에서도 동일한 증상이 나타난다. 이러한 갱년기 질환은 갱년기성 골다공증, 안면홍조, 복부비만, 자궁위축, 인지장애, 알츠하이머, 혈류장애, 다한증 및 피부 노화 등의 신체적인 변화뿐만 아니라 우울증, 집중력저하, 불면, 두통, 이명, 신경과민 등의 정신신경계통에서 증상을 나타내므로 삶의 질을 저하시키는 중요한 원인이 된다. 상기 갱년기 질환이 심각한 경우에는 호르몬요법 등을 사용하기도 하나 이러한 호르몬 요법은 다양한 부작용을 수반할 수 있으므로 세심한 주의를 필요로 한다.
In addition, menopausal disease, that is, around the age of 50 to maintain female sexual function, as well as blood circulation, weight control, bone management and a variety of functions such as helping to reduce the secretion of estrogen, Even if estrogen deficiency is caused by other causes, such as ovariectomy and ovarian dysfunction, the same symptoms appear. These menopausal symptoms are not only physical changes such as menopausal osteoporosis, facial flushing, abdominal obesity, uterine atrophy, cognitive disorders, Alzheimer's disease, blood flow disorders, hyperhidrosis and skin aging, but also depression, concentration loss, insomnia, headache, tinnitus, Of the psychiatric nervous system, which is a major cause of depression in the quality of life. If the menopausal symptoms are severe, hormone therapy may be used. However, such hormone therapy may be accompanied by various side effects, so careful attention is required.
이에 본 발명자들은 대사성 골질환 또는 갱년기 질환을 예방 및 치료할 수 있는 물질을 찾고자 많은 연구를 수행하였으며, 그 결과로 황백 추출물의 발효물이 효과적으로 파골세포 분화를 억제하고 골량을 증가시키며, 복부지방 감소 및 자궁위축 저해 효과를 나타내어, 상기 발효물을 이용하여 대사성 골질환 또는 갱년기 질환을 예방 또는 치료할 수 있음을 확인하고, 본 발명을 완성하였다.
Accordingly, the present inventors have conducted extensive research to find substances capable of preventing or treating metabolic bone diseases or menopausal diseases. As a result, it has been found that the fermented product of the yellow rice extract effectively inhibits osteoclast differentiation, increases bone mass, The present inventors have found that the above fermented product can be used to prevent or treat metabolic bone disease or menopausal disease, thereby completing the present invention.
본 발명의 하나의 목적은 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating metabolic bone disease or menopausal disease which comprises a fermented yellowish white as an active ingredient.
본 발명의 다른 목적은 황백 발효물을 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 개선용 건강기능식품을 제공하는 것이다.Another object of the present invention is to provide a health functional food for preventing or ameliorating a metabolic bone disease or menopausal disease including a yellowish white fermented product.
본 발명의 또 다른 목적은 황백 발효물을 이용하여 대사성 골질환 또는 갱년기 질환을 예방 또는 치료하는 방법을 제공하는 것이다.
It is still another object of the present invention to provide a method for preventing or treating metabolic bone disease or menopausal disease using a fermented yellow fermented product.
상기 목적을 달성하기 위한 하나의 실시양태로서, 본 발명은 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물을 제공한다.
As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating metabolic bone disease or menopausal disease, which comprises a yellowish white fermented product as an active ingredient.
본 발명에서 용어 "황백(Phellodendron amurensis)"이란, 운향과의 갈잎큰키나무로, 다른 이름으로는 황벽나무, 벽목, 황벽, 벽피, 황파라, 황백률, 황피수, 회피백, 화황백, 자멱, 소벽, 단환, 황경피나무, 황경나무라고도 부른다. 주로 깊은 산에서 자라며, 나무껍질은 흑회색에서 연한 회색이며 코르크가 발달하여 깊이 갈라진다. 쓴맛이 나는 속껍질의 색깔이 선명한 개나리 꽃잎보다도 더 노란빛을 띠어 황벽나무라는 이름이 붙여졌다. 동아시아에 약 9종이 있으며, 한국에는 황벽나무(황경나무, 황경피나무), 넓은잎 황벽나무(큰황경나무, 북황경나무), 섬황경나무(섬황벽), 털황경피나무(털황벽)가 자라고 있다. 약재로서, 황백은 일반적으로 상기 황경피나무의 껍질을 말린 것을 지칭하기도 한다. 봄부터 여름 사이에 껍질을 벗겨 겉껍질은 벗겨 버리고 햇빛에 말린다. 맛은 쓰고 성질은 차며, 항균 및 소염작용 등을 나타내는 것으로 알려져 있다. 열매의 정유성분은 만성기관지염으로 인한 진해, 거담, 천식을 가라앉히는 효과가 탁월하다고 보고된 바 있다. 탕약, 산제, 환약의 형태로 복용하며, 외용약으로 쓸 때는 가루로 내어 기초제에 개어서 바른다.
The term "Phellodendron amurensis " in the present invention refers to a black-faced black-faced tree with an almond tree, and in other names, an almond tree, an almond tree, an almond tree, , Sidewall, monoclinia, fenugreek forest, and yellow tree. It grows mainly in deep mountains, the bark is black gray to light gray and the cork develops deeply. The color of the bitter bitter bark is more yellowish than the vigorous forsythia petals, and it is named " There are about nine species in East Asia, and in Korea there are eight species of primrose trees (broadleaved trees, broadleaf trees), broad-leaved trees (large yellowish trees, northerly trees), islanded yellow trees have. As a medicinal substance, yellowish white generally refers to drying the husks of the above-mentioned yellow-berry trees. Peel off the skin from spring to summer and dry in the sun. It is known that it is used for flavor, coldness, antibacterial and anti-inflammatory action. The essential oil component of the fruit has been reported to exert an excellent effect of quenching chinhae, genomes and asthma caused by chronic bronchitis. Take it in the form of hot water, powders, or pills. When you use it as an external medicine, take it out with powder and apply it to the foundation.
한편, 상기 황백 추출물을 발효시키기 위해서 유산균을 사용하는 것이 바람직하며, 상기 유산균으로는 분리균주 또는 시판중인 다양한 유산균을 제한없이 사용할 수 있다. 특별히 이에 제한되지 않으나, 락토바실루스 속(Lactobacillus sp.), 스트렙토코커스 속(Streptococcus sp.), 비피도박테리움 속(Bifidobacterium sp.), 락토코커스 속(Lactococcus sp.), 페디오코커스 속(Pediococcus sp.), 또는 류코노스톡속(Leuconostoc sp.)의 미생물 등을 사용할 수 있고, 바람직하게는 락토바실루스 속 미생물을 사용할 수 있으며, 보다 바람직하게는 락토바실루스 카제이 균주를 사용할 수 있으며, 가장 바람직하게는 락토바실루스 카제이 KFRI 127(Lactobacillus casei KFRI 127)을 사용할 수 있다.On the other hand, it is preferable to use lactic acid bacteria to ferment the yellowish white extract. As the lactic acid bacteria, isolated strains or various commercially available lactic acid bacteria may be used without limitation. But are not limited to, the genus Lactobacillus sp.), in Streptococcus (Streptococcus sp .), the genus Bifidobacterium sp.), in Lactococcus (Lactococcus sp .), the genus Pediococcus sp .), or leuconostoc ( Leuconostoc sp.), and of the like microorganism, preferably a Lactobacillus may be used in micro-organisms, more preferably Lactobacillus can be used for Bacillus casei strain, and most preferably Lactobacillus casei KFRI 127 (Lactobacillus casei KFRI 127) can be used.
본 발명에서 용어 "발효"는 미생물이나 균류 등을 이용해 유기물을 분해하여 인간에게 유용한 물질을 얻어내는 과정을 의미하며, 상기 발효과정에 의해 생성된 물질을 "발효물"이라고 한다. 상기 발효에 사용하는 미생물이나 균류의 종류에 따라, 젖산 발효(젖산균), 알콜 발효(효모), 프로피온산 발효(프로피온산균), 메탄 발효(메탄세균), 유산균 발효(유산균) 등으로 구분될 수 있다.In the present invention, the term "fermentation" means a process of decomposing organic matter using microorganisms or fungi to obtain a substance useful to humans, and the substance produced by the fermentation process is called "fermentation product ". Fermentation (lactic acid bacteria), alcohol fermentation (yeast), propionic acid fermentation (propionic acid bacteria), methane fermentation (methane bacteria), lactic acid fermentation (lactic acid bacteria), and the like depending on the kinds of microorganisms or fungi used for the fermentation .
본 발명에서 용어 "유산균 발효물"이란, 유산균이 성장할 수 있는 배지에 유산균을 접종하고 배양한 배양물로부터 수득한 배양결과물을 의미한다. 본 발명에서 는 황백 열수추출물에 유산균을 접종하여 배양한 배양물로부터 수득한 배양상등액 또는 배양상등액의 건조물을 의미한다.The term "lactobacillus fermented product " in the present invention means a cultured product obtained from a culture obtained by inoculating lactic acid bacterium into a medium in which lactic acid bacteria can grow. The term " culture supernatant " or " culture supernatant solution "
바람직하게, 본 발명의 조성물은 파골세포 분화를 억제하고, 골량을 증가시키며, 복부지방을 감소시키고, 자궁위축을 저해하는 효과를 나타내므로 특히, 난소기능 저하 또는 에스트로겐 분비 감소로 인해 유발되는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료에 사용될 수 있다.Preferably, the composition of the present invention inhibits osteoclast differentiation, increases bone mass, decreases abdominal fat, and inhibits uterine atrophy. Therefore, the composition of the present invention is particularly useful as a metabolic bone Can be used for the prevention or treatment of diseases or menopausal diseases.
본 발명에서 용어 "대사성 골질환"이란, 파골세포의 과다한 생성 및/또는 활성으로 인해 나타나는 상태 또는 질병을 의미하는 것으로, 골량 저하 질환을 포함한다. 상기 골량 저하 질환이란 골밀도의 저하, 골조직의 연화 등의 증상을 수반하는 골량의 저하가 나타나는 상태 또는 질환을 의미한다. 상기 대사성 골질환의 비제한적인 예로는 골다공증(osteoporosis), 골연화증(osteomalacia), 골감소증(osteopenia), 골위축(bone atrophy), 섬유성골이형성증(fibrous dysplasia), 파제트병(Paget's disease), 고칼슘혈증(hypercalcemia), 뼈의 종양성 파괴(neoplastic bone destruction), 암 관련 골재흡수 질병, 골용해(osteolysis), 골관절염(osteoarthritis), 치주질환, 골성장장애 및 류마티스관절염 등이 있다.The term "metabolic bone disease" in the present invention means a condition or disease caused by excessive production and / or activity of osteoclasts, and includes diseases with lowered bone mass. The term "lowering bone disease" refers to a condition or disease in which a decrease in bone mass accompanying symptoms such as a decrease in bone density and softening of bone tissue occurs. Non-limiting examples of the metabolic bone disease include osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrous dysplasia, Paget's disease, hypercalcemia, neoplastic bone destruction, cancer-associated aggregate absorption disease, osteolysis, osteoarthritis, periodontal disease, osteoarthritis, and rheumatoid arthritis.
또한 본 발명에서 용어 "갱년기 질환"이란, 갱년기 즉, 50세를 전후하여 여성호르몬인 에스트로겐의 분비가 저하되면서 발병하는 질환을 의미한다. 에스트로겐은 여성 성기능을 유지할 뿐만 아니라 혈액순환, 체중조절, 뼈관리를 돕는 등의 다양한 기능을 한다. 따라서, 갱년기가 되어 에스트로겐 분비가 감소하면 이로 인한 여러가지 신체 변화를 수반된다. 상기 갱년기 질환의 주된 원인은 에스트로겐 분비 저하로 난소 절제, 난소 기능저하 등 다른 원인에 의한 에스트로겐 결핍에서 오는 질환도 본 발명의 갱년기 질환에 포함된다. 상기 갱년기 질환의 비제한적인 예로는 갱년기성 골다공증, 안면홍조, 복부비만, 자궁위축, 인지장애, 알츠하이머, 혈류장애, 다한증 및 피부 노화 등이 있다.The term "menopausal disease" in the present invention means a disease caused by a decrease in the secretion of estrogen, which is a female hormone, in menopause, that is, around 50 years old. Estrogen not only maintains female sexual function, but also has various functions such as blood circulation, weight control, and bone management. Therefore, when estrogen secretion decreases as it becomes a menopause, it causes various body changes. The main causes of the menopausal disease include osteoporosis due to lowering of estrogen secretion, diseases caused by estrogen deficiency due to other causes such as ovarian function deterioration, and the like. Non-limiting examples of such menopausal diseases include menopausal osteoporosis, facial flushing, abdominal obesity, uterine atrophy, cognitive disorders, Alzheimer's disease, blood flow disorders, hyperhidrosis and skin aging.
본 발명에서 용어 "예방"이란 본 발명에 따른 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물의 투여로 대사성 골질환 또는 갱년기 질환의 발병을 저해 또는 지연시키는 모든 행위를 의미한다.The term "prevention" in the present invention refers to the administration of a pharmaceutical composition for preventing or treating metabolic bone disease or menopausal disease comprising the yellowish white fermented product according to the present invention as an active ingredient to inhibit or delay the onset of metabolic bone disease or menopausal disease It means all the acts that you do.
본 발명에서 용어 "치료"란 본 발명에 따른 황백 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물의 투여로 대사성 골질환 또는 갱년기 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.
The term "treatment" in the present invention means the administration of a pharmaceutical composition for the prevention or treatment of metabolic bone disease or menopausal disease comprising the fermented yellowish white matter according to the present invention as an active ingredient to improve or ameliorate symptoms of metabolic bone disease or menopausal disease Means any action that is changed.
본 발명의 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물의 유효성분으로, 바람직하게는 황백 열수추출물에 유산균을 접종하여 발효시킨 결과로서 얻어진 유산균 발효물을 포함할 수 있고, 이때 사용된 유산균은 락토바실루스 속, 스트렙토코커스 속, 비피도박테리움 속, 락토코커스 속, 페디오코커스 속, 류코노스톡 속 등의 미생물 등일 수 있으며, 바람직하게는 락토바실루스 속 미생물 일 수 있으며, 보다 바람직하게는 락토바실루스 카제이 균주이며, 가장 바람직하게는 락토바실루스 카제이 KFRI 127이 될 수 있다.
The active ingredient of the pharmaceutical composition for preventing or treating metabolic bone disease or menopausal disease of the present invention may preferably include fermented lactic acid bacteria obtained as a result of inoculating lactic acid bacteria into fermented Hwangyong hot-water extract, The lactic acid bacteria may be microorganisms such as Lactobacillus, Streptococcus, Bifidobacterium, Lactococcus, Pediococcus, and Leuconostoch, preferably microorganisms of the genus Lactobacillus, Is a lactobacillus casei strain, and most preferably Lactobacillus casei can be KFRI127.
본 발명의 일 실시예에 의하면, 황백 열수추출물에 락토바실루스 카제이 KFRI 127을 접종하여 발효시킨 유산균 발효물이 RANKL에 의해 유도된 TRAP(tartrate-resistant acid phosphatase) 활성 및 이에 의한 파골세포의 분화를 억제하는 효과를 나타내고(도 1), 발효시키지 않은 황백 추출물보다 우수한 골조직 회복 효과가 있으며(도 3), 복부지방의 증가를 억제하고 자궁위축을 현저히 완화하는 효과를 나타냄을 확인하였다(도 4).According to one embodiment of the present invention, fermented lactic acid bacteria fermented by inoculation of Lactobacillus casei KFRI 127 into a hydrothermal extract of HwangByong can inhibit RANKL-induced TRAP (tartrate-resistant acid phosphatase) activity and osteoclast differentiation (Fig. 1). It was found that the extract had better bone restoration effect than the non-fermented yellowish white extract (Fig. 3), and suppressed the increase of abdominal fat and significantly alleviated uterine atrophy (Fig. 4) .
따라서, 이와 같은 결과를 근거로 락토바실루스 카제이 KFRI 127을 이용한 발효물을 유효성분으로 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물이 발효시키지 않은 황백 추출물 원시료 보다 대사성 골질환 또는 갱년기 질환의 예방 또는 치료에 유용하게 사용될 수 있을 뿐만 아니라, 이에 의해 유발되는 증상 또는 합병증을 예방 또는 치료할 수 있을 것으로 기대된다.Therefore, based on these results, a pharmaceutical composition for the prevention or treatment of metabolic bone disease or menopausal disease comprising fermentation product of Lactobacillus casei KFRI 127 as an active ingredient is more preferable than a fermented raw material of yellowish white extract, Or menopausal disease, as well as to prevent or treat the symptoms or complications caused thereby.
본 발명의 대사성 골질환 또는 갱년기 질환의 예방 또는 치료용 약학적 조성물은 추가로 약학적으로 허용가능한 담체, 부형제 또는 희석제를 포함할 수 있다.The pharmaceutical composition for the prevention or treatment of metabolic bone disease or menopausal disease of the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.
본 발명의 치료용 조성물에 사용될 수 있는 약학적으로 허용가능한 담체, 부형제 및 희석제의 예로는 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 칼슘 카보네이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시 벤조에이트, 프로필하이드록시 벤조에이트, 탈크, 마그네슘 스테아레이트, 광물유 등을 들 수 있다.Examples of pharmaceutically acceptable carriers, excipients and diluents that can be used in the therapeutic composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, Gelatin, calcium phosphate, calcium silicate, calcium carbonate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
본 발명의 약학적 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 제형화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 치료용 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트, 수크로즈 또는 락토즈, 젤라틴 등을 혼합하여 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.
The pharmaceutical composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method . In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like which are generally used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
또 하나의 양태로서, 본 발명은 상기 발효물을 제조하는 방법을 제공한다.In another aspect, the present invention provides a method of producing the fermented product.
구체적으로 본 발명의 황백 발효물을 제조하는 방법은 황백 추출물에 유산균을 접종하여 발효시키는 단계를 포함한다. 상기 황백 추출물은 열수추출물 또는 C1 내지 C6 알콜추출물 일 수 있다. 이때, 유산균은 특별히 이에 제한되지 않으나, 락토바실루스 속, 스트렙토코커스 속, 비피도박테리움 속, 락토코커스 속, 페디오코커스 속, 류코노스톡 속 등의 미생물을 사용할 수 있고, 바람직하게는 락토바실루스 속 미생물, 보다 바람직하게는 락토바실루스 카제이 균주, 가장 바람직하게는 락토바실러스 카제이 KFRI 127을 사용할 수 있다. 유산균의 발효조건은 특별히 이에 제한되지 않으나, 4 내지 45 ℃의 온도 및 1일 내지 2년 동안 수행함이 바람직하다. 보다 바람직하게는, 황백 추출물에 유산균을 접종하여 35 내지 45 ℃의 온도 및 1 내지 3일 동안 배양할 수 있다. 보다 바람직하게는, 황백 추출물에 유산균을 접종하여 37℃에서 48시간 배양할 수 있다.Specifically, the method for producing the yellowish white fermented product of the present invention includes a step of inoculating the yellowish white extract with lactic acid bacteria and fermenting the same. The yellowish white extract may be a hot water extract or a C 1 to C 6 alcohol extract. The lactic acid bacteria are not particularly limited, but microorganisms such as lactobacillus, Streptococcus, Bifidobacterium, Lactococcus, Pediococcus, and Leuconostoch can be used, and preferably lactobacillus More preferably Lactobacillus casei strain, and most preferably Lactobacillus casei KFRI 127 can be used. The fermentation conditions of the lactic acid bacteria are not particularly limited, but it is preferable that the fermentation is carried out at a temperature of 4 to 45 DEG C and for 1 to 2 years. More preferably, the yellowish white extract may be inoculated with the lactic acid bacteria and incubated at a temperature of 35 to 45 DEG C for 1 to 3 days. More preferably, the yellowish white extract can be inoculated with lactic acid bacteria and cultured at 37 DEG C for 48 hours.
본 발명의 일 실시예에서는, 본 발명에 따른 황백 발효물을 제조하기 위해 황백의 열수추출물에, 1%(v/v)에 해당하는 양의 유산균 즉, 1 내지 5×106 CFU/㎖ 농도의 락토바실루스 카제이 KFRI 127을 접종하여 37 ℃에서 48시간 배양하여 발효시켜 배양물을 수득하고, 동결건조하여 발효물을 제조하였다.
In one embodiment of the present invention, in order to prepare the fermented yellowish white fermented product according to the present invention, the yellowish white hot-water extract is mixed with 1% (v / v) lactic acid bacteria in an amount of 1 to 5 × 10 6 CFU / Of Lactobacillus casei KFRI 127 was inoculated and cultured at 37 占 폚 for 48 hours for fermentation to obtain a culture, followed by lyophilization to prepare a fermented product.
또 하나의 양태로서, 본 발명은 황백 발효물을 포함하는 대사성 골질환 또는 갱년기 질환의 예방 또는 개선용 건강기능식품을 제공한다.In another aspect, the present invention provides a health functional food for preventing or ameliorating a metabolic bone disease or menopausal disease comprising a yellowish white fermented product.
구체적으로, 본 발명에 따른 상기 발효물은 대사성 골질환 또는 갱년기 질환의 예방 또는 개선을 목적으로 식품 또는 음료에 첨가될 수 있는데, 식품 종류는 특별히 제한되지 않으며, 예를 들어, 과자류, 빵류, 면류 등과 같은 각종 식품류, 물, 청량음료, 과실음료 등의 드링크류, 껌, 차, 비타민 복합제, 조미료류, 건강기능 식품류 등이 있다. 이때, 식품 또는 음료 중의 상기 발효물의 양은 일반적으로 본 발명의 건강기능식품 조성물의 경우는 전체 식품 중량의 0.01 내지 15 중량%, 바람직하게는 0.1 내지 5 중량%로 가할 수 있으며, 건강음료 조성물에는 100 을 기준으로 0.01 내지 5.0 g, 바람직하게는 0.01 내지 1.0 g의 비율로 첨가할 수 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 본 발명의 발효물을 함유하고 있기 때문에, 상기 발효물이 지닌 대사성 골질환 또는 갱년기 질환의 예방 또는 치료 효과를 충분히 활용할 수 있는 식품이다.Specifically, the fermented product according to the present invention may be added to food or beverage for the purpose of preventing or improving metabolic bone disease or menopausal disease. The type of food is not particularly limited, and examples thereof include confectionery, Etc., water, soft drinks, fruit drinks, gum, tea, vitamin complex, seasoning, and health functional foods. In this case, the amount of the fermented product in the food or beverage may be generally 0.01 to 15% by weight, preferably 0.1 to 5% by weight of the total food weight in the case of the health functional food composition of the present invention, May be added in a proportion of 0.01 to 5.0 g, preferably 0.01 to 1.0 g, based on the total weight of the composition. Since the health functional food of the present invention thus obtained contains the fermented product of the present invention, it is a food which can fully utilize the preventive or therapeutic effect of metabolic bone disease or menopausal disease of the fermented product.
본 발명의 건강기능식품은 기재로 되는 식품의 제조공정 중에 상술한 본 발명의 발효물을 첨가하는 공정 또는 식품의 제조 후에 상술한 본 발명의 발효물을 첨가하는 공정에 의하여 용이하게 제조될 수 있다. 이때, 필요에 따라 맛과 냄새 교정제를 첨가할 수도 있다.The health functional food of the present invention can be easily produced by adding the fermented product of the present invention described above to the substrate for producing the food or by adding the fermented product of the present invention described above after the production of the food . At this time, a taste and odor corrector may be added as needed.
아울러, 상기 건강기능식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 건강기능식품은 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이 같은 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 본 발명의 건강기능식품 100 중량부 당 약 20 중량부 이하의 범위 내에서 선택되는 것이 일반적이다.
In addition, the health functional food may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate, etc.), pectic acid and its salts, Salts, organic acids, protective colloid concentrating agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the health functional food of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. Such components may be used independently or in combination. The proportion of such additives is generally selected within a range of about 20 parts by weight or less per 100 parts by weight of the health functional food of the present invention.
또 하나의 양태로서, 본 발명은 대사성 골질환 또는 갱년기 질환의 예방 또는 치료방법을 제공한다. 상기 방법은 약학적으로 유효한 양의 황백 발효물을, 치료를 필요로 하는 개체에 투여하는 단계를 포함한다.In another aspect, the present invention provides a method for preventing or treating metabolic bone disease or menopausal disease. The method comprises administering a pharmaceutically effective amount of a yellowish fermented product to a subject in need of treatment.
본 발명에서 용어 "개체"는 파골세포 분화억제, 복부지방 증가 억제 및 자궁위축 억제 효과를 갖는 본 발명에 따른 약학적 조성물의 투여에 의해 증상이 호전될 수 있는 대사성 골질환 또는 갱년기 질환을 가진, 인간을 포함하여 말, 양, 돼지, 염소, 낙타, 영양, 개, 고양이 등의 포유동물일 수 있으나, 이에 제한되지 않는다. 파골세포 분화억제, 복부지방 증가 억제 및 자궁위축 억제 효과를 갖는 본 발명의 발효물을 개체에게 투여함으로써, 대사성 골질환 또는 갱년기 질환을 효과적으로 예방 및 치료할 수 있다.In the present invention, the term "individual" refers to a patient having metabolic bone disease or menopausal disease whose symptoms can be improved by the administration of the pharmaceutical composition according to the present invention having osteoclast differentiation inhibition, But are not limited to, humans, mammals such as horses, sheep, pigs, goats, camels, nutrition, dogs, cats and the like. By administering the fermented product of the present invention having an osteoclast differentiation inhibition, an abdominal fat increase inhibition and an inhibition of uterine atrophy, the metabolic bone disease or menopausal disease can be effectively prevented and treated.
본 발명에서 용어 "투여"는 어떠한 적절한 방법으로 동물에게 소정의 물질을 도입하는 것을 의미하며, 본 발명에 다른 치료용 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명의 발효물은 유효성분이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.The term "administering" in the present invention means introducing a predetermined substance into an animal by any appropriate method, and the administration route of the other therapeutic composition according to the present invention may be administered orally, May be administered parenterally. The fermentation product of the present invention can also be administered by any device capable of moving the active ingredient into the target cell.
본 발명에서 용어 "약학적으로 유효한 양"은 의학적 치료에 적용가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 성별, 연령, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 발효물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있다. 또한 본 발명의 발효물은 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다. 구체적으로 본 발명의 치료용 조성물은 경구투여 또는 정맥투여가 바람직하다.The term "pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the sex, age, The activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The fermented product of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent and may be administered sequentially or simultaneously with a conventional therapeutic agent. The fermentation product of the present invention can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. Specifically, the therapeutic composition of the present invention is preferably administered orally or intravenously.
본 발명에 따른 발효물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여 경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 발효물은 1일 10 내지 1000 mg/kg으로, 바람직하게는 10 내지 500 mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다.
The preferred dosage of the fermented product according to the present invention varies depending on the condition and weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the fermented product of the present invention can be administered at 10 to 1000 mg / kg, preferably 10 to 500 mg / kg per day. The administration may be carried out once a day or divided into several times.
본 발명의 일 실시예에 의하면, 황백 발효물은 파골세포 분화를 억제하고, 골량을 증가시키며, 복부지방을 감소시키고, 자궁위축을 저해하는 효과를 나타냈고, 이러한 효과는 황백 발효물에서 나타나며, 황백 추출물 원시료에서 보다 현저히 향상된 효과이다.
According to one embodiment of the present invention, the fermented yellow fermented product inhibits osteoclast differentiation, increases bone mass, decreases abdominal fat, and inhibits uterine atrophy. This effect appears in yellowish white fermented product, It is a remarkably improved effect than that of the original sample.
본 발명에 따른 황백 발효물은 파골세포 분화를 억제하고, 골량을 증가시키며, 복부지방을 감소시키고, 자궁위축을 저해하는 효과를 나타내므로, 약학적 조성물 또는 건강기능식품의 형태로 제조되어 대사성 골질환 또는 갱년기 질환의 예방 또는 치료에 널리 활용될 수 있을 것이다.
The fermented product according to the present invention inhibits osteoclast differentiation, increases bone mass, reduces abdominal fat, and inhibits uterine atrophy. Thus, the fermented product is produced in the form of a pharmaceutical composition or a health functional food, Diseases or menopausal diseases.
도 1은 본 발명에 따른 황백 열수추출물(황백) 및 황백 유산균 발효물(황백발효) 처리농도에 따른 RANKL 유도된 가) TRAP 활성 및 나) TRAP 양성 다핵성 파골세포(Oc; osteoclast) 수를 나타낸 도이다.
도 2는 본 발명에 따른 황백 열수추출물(황백) 및 황백 유산균 발효물(황백발효) 처리 농도별 세포독성을 나타낸 도이다.
도 3은 본 발명에 따른 황백 열수추출물(황백) 및 황백 유산균 발효물(황백발효) 투여에 따른 가) 마이크로-CT 이미지, 나) 해면골(Trabecular bone)의 조직부피에 대한 골부피(BV/TV; bone volume/tissue volume), 섬유주 수(Tb. N; Trabecular number), 섬유주 두께(Tb. Th; trabecular thickness) 및 섬유주 분리(Tb. Sp; Trabecular separation)를 나타낸 도이다.
도 4는 본 발명에 따른 황백 열수추출물(황백) 및 황백 유산균 발효물(황백발효) 투여에 따른 가) 복부지방 무게 및 나) 자궁 무게를 나타낸 도이다.1 shows the RANKL-induced a) TRAP activity and the number of TRAP-positive polynuclear osteoclasts (Oc) according to the treatment concentration of the fermented product of yellowish white hot water extract (yellow white) and yellow lactic acid bacteria (yellow white fermentation) according to the present invention .
FIG. 2 is a graph showing cytotoxicity according to the treatment concentration of the fermented product of fermented fermented product of fermented fermented fermented product of fermented fermented product of fermented fermented product of fermented fermented product of fermented fermented product of fermented fermented product of fermented fermented product of fermented fermented fermented product of fermented fermented fermented product
FIG. 3 is a micro-CT image obtained by the administration of the fermented product of yellowish white hot water extract (yellow white) and white lactic acid fermented product (yellowish white fermentation) according to the present invention, b) bone volume (BV / TV) for the tissue volume of the trabecular bone Trabecular number, Tb (trabecular thickness), and trabecular separation (Tb, Sp) are shown in Fig.
FIG. 4 is a graph showing a) abdominal fat weight and b) uterine weight according to the administration of the fermented product of yellowish white hot water extract (yellow white)
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
제조예Manufacturing example
1: One:
황백Yellowish white
열수추출물의Of hot-water extract
제조 Produce
황백 1 kg을 10 L 생수에 첨가한 후 115℃에서 3시간 동안 열탕추출(경서추출기 Cosmos-6000)하였다. 추출물은 표준 시험용 체(standard testing sieve, 106 ㎛)로 여과하여 황백 열수추출물을 수득하였다.
1 kg of yellowish white was added to 10 L of bottled water and then extracted with hot water (Cosmos-6000) at 115 ° C for 3 hours. The extract was filtered with a standard testing sieve (106 mu m) to obtain a yellowish white hot water extract.
실시예Example
1: One:
황백Yellowish white
유산균 Lactobacillus
발효물의Fermented
제조 Produce
황백 유산균 발효물을 제조하기 위하여 한국식품연구원(KFRI)으로부터 락토바실루스 속(Lactobacillus sp .) 균주를 제공받았다. 하기 표 1에 본 발명에 사용된 발효 균주의 정보를 기재하였다.To prepare fermented products of fermented fermented Lactobacillus acidus, a fermented product of Lactobacillus ( Lactobacillus sp. sp . ) Strain. Table 1 below shows the information of the fermentation strains used in the present invention.
고유 균주번호Organism
Unique strain number
구체적으로, 상기 제조예 1에서 수득한 황백 열수추출물에 총 부피의 1%(v/v)에 해당하는 양의 유산균(1 내지 5×106 CFU/㎖)을 첨가하고 37℃에서 48시간 동안 배양하였다. 이와 같이 제조된 황백 유산균 발효물은 동결 건조하여 사용하기 전까지 -20℃에 보관하였다.
Specifically, lactic acid bacteria (1 to 5 × 10 6 CFU / ml) in an amount corresponding to 1% (v / v) of the total volume was added to the white and blue hot water extract obtained in Preparation Example 1 and incubated at 37 ° C. for 48 hours Lt; / RTI > The thus fermented fermented fermented fermented fermented lactic acid fermented product was stored at -20 ° C. until it was freeze-dried.
실시예Example
2: 2:
TRAPTRAP
활성 및 파골세포 분화 Active and osteoclast differentiation
상기 실시예 1에서 제조한 황백 유산균 발효물가 파골세포 분화에 미치는 영향을 확인하였다. 이를 위하여 파골세포는 마우스의 골수세포로부터 수득하였다. 구체적으로 상기 마우스의 골수세포를 M-CSF(60 ng/㎖)와 10% FBS를 함유한 α-MEM에 3일 동안 배양하여 골수세포 유래 대식세포(BMM)를 수득하였으며, 이를 파골세포 전구세포로 사용하였다. 파골세포를 생성하기 위해, 상기 수득한 BMM을 M-CSF(60 ng/㎖) 및 RANKL(100 ng/㎖)을 포함하는 배지에 4일 동안 배양하였고, 같은 배양조건에서 BMM에 황백 열수추출물과 이의 유산균 발효물을 다양한 농도(2.5, 5, 10, 20, 40, 80 및 160 ㎍/㎖)로 처리하였다. 배양된 세포는 TRAP 활성 측정을 위하여 10% 포르말린으로 고정한 후 기질(p-니트로페닐 포스페이트)을 이용하여 405 nm에서 흡광도(optical density; OD)를 측정하였다. 또한, 다핵성 파골세포 분화를 분석하기 위하여 나프톨 AS-MS 포스페이트 및 패스트 레드 바이올렛 LB 염(fast red violet LB salt)을 이용하여 TRAP 염색하여 현미경으로 관찰하고 핵이 3개 이상인 TRAP 양성세포(파골세포, osteoclast; Oc)를 계수하였다. 데이터는 평균과 표준오차로 나타내었다. 그 결과를 도 1에 나타내었다.The effect of the fermented fermented product of fermented fermented fermented lactic acid bacteria prepared in Example 1 on osteoclast differentiation was confirmed. For this purpose, osteoclasts were obtained from bone marrow cells of mice. Specifically, the bone marrow cells of the mice were cultured in α-MEM containing M-CSF (60 ng / ml) and 10% FBS for 3 days to obtain bone marrow-derived macrophages (BMM) Respectively. To produce osteoclasts, the BMM obtained was cultured in a medium containing M-CSF (60 ng / ml) and RANKL (100 ng / ml) for 4 days, The lactic acid fermented product thereof was treated with various concentrations (2.5, 5, 10, 20, 40, 80 and 160 / / ml). The cultured cells were fixed with 10% formalin to measure TRAP activity, and the optical density (OD) was measured at 405 nm using a substrate (p-nitrophenylphosphate). In order to analyze the polynuclear osteoclast differentiation, TRAP staining was performed using naphthol AS-MS phosphate and fast red violet LB salt (microscopic observation), and TRAP-positive cells having three or more nuclei , osteoclast (Oc) were counted. Data are presented as mean and standard error. The results are shown in Fig.
도 1 가)에 나타난 바와 같이, 황백 열수추출물을 10, 20, 40, 80 및 160 ㎍/㎖로 처리한 세포에서 각각 29, 59, 90, 98 및 99%의 TRAP 활성 억제효과가 나타났으며, 황백 유산균 발효물을 20, 40, 80 및 160 ㎍/㎖로 처리한 세포에서 각각 23, 61, 91 및 98%의 TRAP 활성 억제효과가 나타났다(스튜던트 t 테스트, ***p＜0.001). 한편, 도 1 나)에 나타난 바와 같이, 황백 열수추출물을 10, 20, 40, 80 및 160 ㎍/㎖로 처리한 세포는 각각 50, 96, 99, 100 및 100%로 파골세포 분화가 억제되었으며, 황백 유산균 발효물을 20, 40, 80 및 160 ㎍/㎖로 처리한 세포는 각각 62, 99, 100 및 100%로 파골세포 분화가 억제되었다(스튜던트 t 테스트,**p＜0.01; ***p＜0.001).
As shown in FIG. 1 a), 29, 59, 90, 98 and 99% inhibition of TRAP activity was observed in cells treated with 10, 20, 40, 80 and 160 ㎍ / , And 23, 61, 91 and 98% inhibition of TRAP activity in cells treated with 20, 40, 80 and 160 ㎍ / ㎖ of fermented white lactic acid bacteria (Student t test, *** p <0.001). As shown in FIG. 1 B, osteoclast differentiation was inhibited by 50, 96, 99, 100 and 100% cells treated with 10, 20, 40, 80 and 160 ㎍ / , Osteoclast differentiation was inhibited in cells treated with 20, 40, 80 and 160 ㎍ / ㎖ of fermented white lactic acid bacteria at 62, 99, 100 and 100%, respectively (Student t test, ** p <0.01; ** * p < 0.001).
실시예Example
3: 세포 독성 3: cytotoxicity
상기 실시예 2에 사용한 BMM 세포(1×104 세포/웰)를 M-CSF(60 ng/㎖)를 함유하는 배지에 3일 동안 다양한 농도의 황백 열수추출물 또는 유산균 발효물 시료을 첨가하여 배양하였다. 세포 계수 키트-8(Cell counting Kit-8; CCK-8. Dojindo Inc.)을 이용하여 450 nm에서 흡광도를 측정함으로써 세포 생존율(cell viability)을 확인하였고, 데이터는 평균과 표준오차로 나타내었다. 그 결과를 도 2에 나타내었다.BMH cells (1 × 10 4 cells / well) used in Example 2 were cultured for 3 days in a medium containing M-CSF (60 ng / ml) with various concentrations of Hwangy White hot-water extract or lactobacillus fermentation samples . Cell viability was determined by measuring the absorbance at 450 nm using Cell Counting Kit-8 (CCK-8, Dojindo Inc.), and the data were expressed as mean and standard error. The results are shown in Fig.
도 2에 나타난 바와 같이, 황백 열수추출물은 80 및 160 ㎍/㎖ 농도로 처리하였을 때, 각각 29 및 41%의 세포독성을 나타낸 반면, 이의 유산균 발효물은 전체 실험농도 즉, 2.5 내지 160 ㎍/㎖ 모두에서 세포독성을 나타내지 않았으며, 오히려, 5, 10, 20, 40, 80 및 160 ㎍/㎖ 농도로 처리한 세포에서 각각 33, 56, 50, 30 및 19%의 세포생장 촉진효과를 나타내었다(스튜던트 t 테스트, ***p＜0.001).
As shown in FIG. 2, the hydrothermal extract of Huang Baek showed cytotoxicity of 29 and 41%, respectively, when treated at the concentrations of 80 and 160 / / ml, whereas the fermented product of the lactic acid bacteria had a total experimental concentration of 2.5 to 160 ㎍ / Ml, but rather showed cell growth promoting effects of 33, 56, 50, 30 and 19% in cells treated with 5, 10, 20, 40, 80 and 160 ㎍ / (Student t test, *** p <0.001).
실시예Example
4: 동물실험 4: Animal experiment
4.1. 실험동물 및 시료 투여4.1. Experimental animal and sample administration
동물실험은 한국한의학연구원 동물실험운영규정을 준수하여 수행하였다. 7주령의 암컷 ICR 마우스(샘타코, 오산시)를 대상으로 7일간의 순화기간을 거친 후, 모의 수술(sham operation; Sham, n=7) 또는 난소 절제술(ovariectomy; OVX, n=20)을 실시하였다. 수술 2주일 후 OVX 시술한 마우스의 OVX군(황백 미처리군) 7마리, 황백 열수추출물 투여군(OVX 후 황백 열수추출물 투여) 6마리, 그리고 황백 유산균 발효물 투여군(OVX 후 황백 유산균 발효물 투여) 7마리로 군분리를 하였다. 이후 4 주간 매일 1회씩 황백 열수추출물 그리고 황백 유산균 발효물을 마우스 kg 당 0.0625 g으로 경구 투여 하였으며, 하기 표 2에 구체적인 대조군 및 실험군의 구성을 나타내었다.Animal experiments were carried out in accordance with Korean Animal Husbandry Laboratories' Animal Experiment Operation Regulations. Seven-week-old female ICR mice (Samtako, Osan) were subjected to a 7-day purification period and then subjected to sham operation (Sham, n = 7) or ovariectomy (OVX, n = 20) Respectively. After 2 weeks of operation, 7 OVX group (non-white rice group), 6 yellowish white hot water extract group (OVX post hydrothermal extract) and 6 yellow rice white lactic acid fermented group administered OVX treated mice The marly group was separated. Then, once a day for 4 weeks, the fermented product of yellowish white hot water and the fermented fermented product of yellowish white lactic acid were orally administered at 0.0625 g per kg of mouse, and the composition of the specific control group and experimental group was shown in Table 2 below.
4.2. 마이크로-CT(4.2. Micro-CT ( micromicro -- computedcomputed tomography)tomography) 분석 analysis
4주간 상기 표 2에 나타난 바와 같이 시료를 투여한 후, 12시간 동안 절식된 마우스의 오른쪽 대퇴골을 분리하여 10% 포르말린으로 고정하였다. 대퇴골을 SMX-90CT 시스템(Shimadzu, Kyoto, Japan)으로 스캔하였다. VG 스튜디오 맥스 1.2.1 프로그램으로 대퇴골의 3차원적 구조를 재구성하였다. 대퇴골의 해면골(trabecular bone)의 조직부피에 대한 골부피(BV/TV; bone volume/tissue volume), 섬유주 수(Tb. N; Trabecular number) 및 섬유주 분리(Tb. Sp; Trabecular separation)는 TRI/3D-BON(RATOC System Engineering, Kyoto, Japan)으로 계산하였고, 데이터는 평균과 측정표준오차로 나타내었다. 그 결과를 도 3에 나타내었다.After administration of the sample as shown in Table 2 for 4 weeks, the right femur of the fasted mouse for 12 hours was separated and fixed with 10% formalin. The femur was scanned with the SMX-90CT system (Shimadzu, Kyoto, Japan). The 3D structure of the femur was reconstructed with the VG Studio Max 1.2.1 program. The bone volume (BV / TV), trabecular number (Tb), and trabecular number (Tb) of the trabecular bone of the femur were measured using TRI / 3D-BON (RATOC System Engineering, Kyoto, Japan), and the data were expressed as mean and standard error of measurement. The results are shown in Fig.
도 3에 나타난 바와 같이, Sham 군과 비교하여 OVX 군은 해면골의 조직부피에 대한 골부피(BV/TV) 33.4%, 섬유주 수(Tb.N) 34.8% 및 섬유주 분리(Tb.Sp) 433.3%로 현저한 골소실을 보였다. OVX 군과 비교하여 황백 열수추출물 투여군에서는 유의적인 변화를 보이지 않았다. 하지만, 유산균 발효물을 투여군에서 Sham과 비교하여 BV/TV가 106%, Tb.N이 99.2%, 및 Tb.Sp가 126.8%로 OVX에 의한 골소실을 현저히 억제함을 보였다(통계분석: 던네트 테스트를 수반하는 일방 ANOVA(one-way ANOVA followed by Dunnett's test), *p＜0.05).
As shown in FIG. 3, the OVX group showed 33.4% of bone volume (BV / TV), 34.8% of trabecular bone (Tb.N) and 43.3% of trabecular meshwork (Tb.Sp) And a significant bone loss was noted. Compared with OVX group, there was no significant change in the hydrothermal extract - treated group. However, compared with Sham in the lactobacillus fermented product group, BV / TV showed 106%, Tb.N 99.2%, and Tb.Sp 126.8% significantly inhibited OVX-induced bone loss compared to Sham (Statistical analysis: One-way ANOVA followed by Dunnett's test with net test, * p <0.05).
4.3. 4.3. 복부지방Abdominal fat 및 자궁 무게 측정 And uterine weighing
4주간 상기 표 2에 나타난 바와 같이 시료를 투여한 후, 12시간 동안 절식된 마우스의 복부지방과 자궁을 적출하여 무게를 측정하였고, 데이터는 평균과 측정표준오차로 나타내었다. 그 결과를 도 4에 나타내었다. After administering the sample as shown in Table 2 for 4 weeks, the abdominal fat and uterus of the fasted mouse for 12 hours were removed and weighed. The data were expressed as mean and standard error of the measurement. The results are shown in Fig.
도 4 가)에 나타난 바와 같이, Sham 군과 비교하여 OVX 군의 복부지방 무게는 198%로 복부지방 증가를 유발하였다. OVX + 황백 군은 OVX군과 비교하여 일부 감소하기는 하였으나, 여전히 Sham 군과 비교하여 유의적인 감소 효능을 나타내지 못했다. 반면, OVX + 황백발효 군은 Sham 군의 90% 수준으로 OVX 군과 비교에서 현저한 복부지방 무게의 감소 효능을 보였다(통계분석: 던네트 테스트를 수반하는 일방 ANOVA, **p＜0.01).As shown in FIG. 4 a), the abdominal fat weight of the OVX group was increased to 198% as compared with the Sham group. OVX + Hwangbuk group showed some decrease compared with OVX group, but still showed no significant decrease effect compared with Sham group. On the other hand, the OVX + yellow fermentation group showed a significant reduction of abdominal fat weight compared to the OVX group at 90% level of the Sham group (statistical analysis: one-way ANOVA with Dunnett test, ** p <0.01).
도 4 나)에 나타난 바와 같이, Sham 군과 비교하여 OVX 군은 30% 수준의 자궁무게로 OVX에 의한 상당한 자궁 위축을 확인하였다. OVX + 황백 군은 OVX군과 비교하여 유의적인 변화가 없었다. 반면, OVX + 황백발효 군은 Sham 군의 70% 수준으로 OVX에 의한 자궁 위축을 현저히 완화하는 효능을 보였다(통계분석: 던네트 테스트를 수반하는 일방 ANOVA, **p＜0.01; ***p＜0.001).
As shown in Fig. 4 (b), OVX group showed significant uterine atrophy by OVX with a 30% level of uterine weight compared with Sham group. There was no significant change in OVX + Hwangbuk group compared with OVX group. On the other hand, the OVX + yellow fermentation group showed a remarkable effect of reducing OVX-induced uterine atrophy by 70% of the Sham group (statistical analysis: one-way ANOVA with Dunnett test, ** p <0.01; *** p ≪ 0.001).
Claims (10)
상기 갱년기 질환은 갱년기성 복부비만 또는 자궁위축인, 약학적 조성물.
A pharmaceutical composition for the prevention or treatment of a menopausal disease comprising a fermented yellowish white as an active ingredient,
Wherein the menopausal disease is menopausal abdominal obesity or uterine atrophy.
상기 황백 발효물은 황백 추출물의 유산균 발효물인 것인 약학적 조성물.
The method according to claim 1,
Wherein the yellowish white fermented product is a fermented product of a fermented product of a yellowish white extract.
상기 황백 추출물의 유산균 발효물은 황백 추출물에 유산균을 접종하고, 4℃ 내지 45℃의 온도에서 및 1일 내지 2년의 시간 동안 발효시켜서 수득하는 것인 약학적 조성물.
The method of claim 2,
Wherein the fermented product of L. acidophilus is obtained by inoculating L. acidophilus with the fermented product of L. acidophilus and fermenting at a temperature of from 4 캜 to 45 캜 for a period of from one to two years.
상기 황백 추출물은 열수추출물 또는 C1 내지 C6 알콜추출물인 것인 약학적 조성물.
The method of claim 3,
Wherein the yellowish white extract is a hot water extract or a C 1 to C 6 alcohol extract.
상기 유산균은 락토바실루스 속(Lactobacillus sp.), 스트렙토코커스 속(Streptococcus sp.), 비피도박테리움 속(Bifidobacterium sp.), 락토코커스 속(Lactococcus sp.), 페디오코커스 속(Pediococcus sp.), 및 류코노스톡 속(Leuconostoc sp.) 미생물로 구성된 군으로부터 선택되는 것인 약학적 조성물.
The method of claim 3,
The lactic acid bacterium belongs to the genus Lactobacillus sp.), in Streptococcus (Streptococcus sp .), the genus Bifidobacterium sp.), in Lactococcus (Lactococcus sp .), the genus Pediococcus sp .), and Leuconostoc sp . sp .) microorganisms.
상기 유산균은 락토바실루스 카제이(Lactobacillus casei) KFRI 127인 것인 약학적 조성물.
6. The method of claim 5,
The lactic acid bacterium may be selected from the group consisting of Lactobacillus casei ) KFRI 127. < / RTI >
상기 갱년기 질환은 난소기능 저하 또는 에스트로겐 분비 감소로 인해 유발되는 것인 약학적 조성물.
The method according to claim 1,
Wherein said menopausal disease is caused by decreased ovarian function or decreased estrogen secretion.
상기 갱년기 질환은 갱년기성 복부비만 또는 자궁위축인, 건강기능식품.
As a health functional food for preventing or improving a menopausal disease including a yellowish white fermented product,
Wherein said menopausal disease is a menopausal abdominal obesity or uterine atrophy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020130082407A KR101577732B1 (en) | 2013-07-12 | 2013-07-12 | Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020130082407A KR101577732B1 (en) | 2013-07-12 | 2013-07-12 | Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150007851A KR20150007851A (en) | 2015-01-21 |
| KR101577732B1 true KR101577732B1 (en) | 2015-12-16 |
Family
ID=52570667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020130082407A KR101577732B1 (en) | 2013-07-12 | 2013-07-12 | Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101577732B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210044406A (en) | 2019-10-15 | 2021-04-23 | 한국한의약진흥원 | Composition for preventing and treating bone diesease comprising extracts of Trachelospermi caulis |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102362968B1 (en) | 2019-11-25 | 2022-02-17 | 주식회사 쎌바이오텍 | Composition for Preventing, Relieving or Treating Climacteric Disorders Comprising Lactic Acid Bacteria and Prebiotics |
-
2013
- 2013-07-12 KR KR1020130082407A patent/KR101577732B1/en active IP Right Grant
Non-Patent Citations (2)
| Title |
|---|
| Evidence-Based Complementary and Alternative Medicine. Hindawi Publishing Corporation. 2012. Article ID 325791, 12 pages* |
| 대한침구의학회지. 2012. 제29권 제6호. 페이지 11-21* |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210044406A (en) | 2019-10-15 | 2021-04-23 | 한국한의약진흥원 | Composition for preventing and treating bone diesease comprising extracts of Trachelospermi caulis |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20150007851A (en) | 2015-01-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101394348B1 (en) | Lactobacillus plantarum DSR920 having effect of treatment and prevention of metabolic or inflammatory diseases | |
| KR20180103772A (en) | Composition for preventing or treating immune diseases comprising mixture of lactic acid bacteria | |
| JP7201837B2 (en) | Composition for prevention, improvement or treatment of obesity or fatty liver disease containing Leuconostoc citreum WIKIM0104 | |
| WO2013127146A1 (en) | Lactobacillus plantarum able to relieve lead toxicity and use thereof | |
| KR102206628B1 (en) | Novel Lactobacillus rhamnosus strain for preventing or treating obesity and the use thereof | |
| JP6898628B2 (en) | Neurodegenerative disease therapeutic agent | |
| KR101252639B1 (en) | Composition for Prevention or Treatment of Osteoporosis Comprising Ssanghwatang and Fermentation Product Thereof with Lactic Acid Bacteria | |
| KR20120100608A (en) | Lactobacillus sakei k101 having an activity for prevention and treatment of immune diseases and inflammatory diseases | |
| KR20080065667A (en) | Lactic acid bacterium having immunoregulatory activity derived from moromi for wine fermentation | |
| CN113508173A (en) | Composition for preventing, ameliorating or treating obesity or fatty liver disease comprising WiKim0103 of Welstonia hernensis | |
| KR102007144B1 (en) | A novel strain of Lactobacillus plantarum SKB1234 having an improving effect on arthritis and a method for producing a mixture of the fermented Achyranthes japonica Nakai extract using the Lactobacillus plantarum SKB1234, Angelica gigas Nakai extract and Eucommia ulmoides Oliver extract | |
| KR101402926B1 (en) | Pharmaceutical composition and functional food for prevention or treatment of bone disease comprising the lactic acid bacteria ferment of hwangryunhaedoktang | |
| KR101770036B1 (en) | Composition comprising Schizandrae Fructus extract asan effective component for preventing and treatingarthritis | |
| KR102139732B1 (en) | Composition for improving immune activity containing lactobacillus | |
| KR101577732B1 (en) | Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease | |
| KR101076223B1 (en) | Composition for treating and preventing obesity or hyperlipidemia comprising fermented oriental herb | |
| US20220095636A1 (en) | Kimchi for preventing or treating helicobacter pylori-associated diseases | |
| KR102452957B1 (en) | Composition for preventing or treating clostridioides difficile infection comprising combination of probiotics | |
| KR101779719B1 (en) | Novel Lactobacillus kefiranofaciens DN1 and composition for treating or preventing constipation comprising the same | |
| CN109221697A (en) | Weaned piglets probiotic feed and preparation method thereof | |
| KR102044659B1 (en) | Comprising composition of fermented Achyranthes japonica Nakai extract Complex for preventing or treating arthritis | |
| KR101973514B1 (en) | Prebiotics Containing Grape seed flour | |
| KR20170029103A (en) | Food composition comprising fermented herb extract for preventing or improving of immunity, dyspepsia, diarrhea and constipation | |
| KR101535077B1 (en) | The products containing probiotic Bifidobacterium lactis HY8101 having activity preventing from insulin resistance, which caused type 2 diabetes mellitus | |
| KR102579159B1 (en) | A novel strain of Saccharomyces boulardii 28-7 and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| E902 | Notification of reason for refusal | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20190926 Year of fee payment: 5 |