JP2022522707A - 骨障害の治療または予防に使用するためのマキベリー抽出物 - Google Patents
骨障害の治療または予防に使用するためのマキベリー抽出物 Download PDFInfo
- Publication number
- JP2022522707A JP2022522707A JP2021550158A JP2021550158A JP2022522707A JP 2022522707 A JP2022522707 A JP 2022522707A JP 2021550158 A JP2021550158 A JP 2021550158A JP 2021550158 A JP2021550158 A JP 2021550158A JP 2022522707 A JP2022522707 A JP 2022522707A
- Authority
- JP
- Japan
- Prior art keywords
- bone
- disease
- pharmaceutical
- nutritional supplement
- use according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000284 extract Substances 0.000 title claims abstract description 27
- 208000020084 Bone disease Diseases 0.000 title claims abstract description 15
- 230000002265 prevention Effects 0.000 title claims abstract description 9
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 57
- 230000007547 defect Effects 0.000 claims abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 230000006378 damage Effects 0.000 claims abstract description 13
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 13
- 208000013558 Developmental Bone disease Diseases 0.000 claims abstract description 12
- 206010072610 Skeletal dysplasia Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 206010061363 Skeletal injury Diseases 0.000 claims abstract description 7
- 206010070918 Bone deformity Diseases 0.000 claims abstract description 6
- 206010010356 Congenital anomaly Diseases 0.000 claims abstract description 6
- 208000010191 Osteitis Deformans Diseases 0.000 claims abstract description 6
- 206010058907 Spinal deformity Diseases 0.000 claims abstract description 6
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 6
- 206010040954 Skin wrinkling Diseases 0.000 claims abstract description 4
- 230000037303 wrinkles Effects 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000004410 anthocyanin Substances 0.000 claims description 12
- 235000010208 anthocyanin Nutrition 0.000 claims description 12
- 229930002877 anthocyanin Natural products 0.000 claims description 12
- 150000004636 anthocyanins Chemical class 0.000 claims description 12
- 208000027418 Wounds and injury Diseases 0.000 claims description 9
- -1 rinses Substances 0.000 claims description 9
- 239000003463 adsorbent Substances 0.000 claims description 8
- 235000021028 berry Nutrition 0.000 claims description 8
- 235000007242 delphinidin Nutrition 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- GCPYCNBGGPHOBD-UHFFFAOYSA-N Delphinidin Natural products OC1=Cc2c(O)cc(O)cc2OC1=C3C=C(O)C(=O)C(=C3)O GCPYCNBGGPHOBD-UHFFFAOYSA-N 0.000 claims description 6
- 239000000287 crude extract Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- JKHRCGUTYDNCLE-UHFFFAOYSA-O delphinidin Chemical compound [O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC(O)=C(O)C(O)=C1 JKHRCGUTYDNCLE-UHFFFAOYSA-O 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 235000013399 edible fruits Nutrition 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 230000007812 deficiency Effects 0.000 claims description 3
- 239000008298 dragée Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000002952 polymeric resin Substances 0.000 claims description 2
- 229920005990 polystyrene resin Polymers 0.000 claims description 2
- 239000007940 sugar coated tablet Substances 0.000 claims description 2
- 229920003002 synthetic resin Polymers 0.000 claims description 2
- 239000007922 nasal spray Substances 0.000 claims 2
- 208000027868 Paget disease Diseases 0.000 claims 1
- 206010043945 Tongue coated Diseases 0.000 claims 1
- 238000007906 compression Methods 0.000 claims 1
- 230000006835 compression Effects 0.000 claims 1
- 239000007941 film coated tablet Substances 0.000 claims 1
- 208000027202 mammary Paget disease Diseases 0.000 claims 1
- 239000002324 mouth wash Substances 0.000 claims 1
- 229940097496 nasal spray Drugs 0.000 claims 1
- 230000011164 ossification Effects 0.000 abstract description 15
- 238000010586 diagram Methods 0.000 abstract description 11
- 208000010392 Bone Fractures Diseases 0.000 abstract description 10
- 206010017076 Fracture Diseases 0.000 abstract description 10
- 230000035876 healing Effects 0.000 abstract description 7
- 208000016738 bone Paget disease Diseases 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000010478 bone regeneration Effects 0.000 abstract description 3
- 230000003412 degenerative effect Effects 0.000 abstract description 2
- 208000035474 group of disease Diseases 0.000 abstract description 2
- 239000008646 Delphinol Substances 0.000 description 25
- 230000000694 effects Effects 0.000 description 15
- 206010065687 Bone loss Diseases 0.000 description 14
- 201000010099 disease Diseases 0.000 description 12
- 238000010172 mouse model Methods 0.000 description 9
- 208000014674 injury Diseases 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 102000003945 NF-kappa B Human genes 0.000 description 7
- 108010057466 NF-kappa B Proteins 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000000963 osteoblast Anatomy 0.000 description 5
- 230000002308 calcification Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 4
- 238000009806 oophorectomy Methods 0.000 description 4
- 230000004072 osteoblast differentiation Effects 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 208000029725 Metabolic bone disease Diseases 0.000 description 3
- 206010049088 Osteopenia Diseases 0.000 description 3
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 3
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 3
- 239000004098 Tetracycline Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 229960002378 oftasceine Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 229960001285 quercetin Drugs 0.000 description 3
- 235000005875 quercetin Nutrition 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960002180 tetracycline Drugs 0.000 description 3
- 229930101283 tetracycline Natural products 0.000 description 3
- 235000019364 tetracycline Nutrition 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- JKYKXTRKURYNGW-UHFFFAOYSA-N 3,4-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(O)=C(O)C(S(O)(=O)=O)=C2 JKYKXTRKURYNGW-UHFFFAOYSA-N 0.000 description 2
- 241000988895 Aristotelia chilensis Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- ZQMDJECDLYTUCE-LCENJUANSA-N Delphinidin-3,5-diglucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=C(O)C=2)OC2=CC(=O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZQMDJECDLYTUCE-LCENJUANSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000004067 Osteocalcin Human genes 0.000 description 2
- 108090000573 Osteocalcin Proteins 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 240000000851 Vaccinium corymbosum Species 0.000 description 2
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 2
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000021014 blueberries Nutrition 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- XENHPQQLDPAYIJ-PEVLUNPASA-O delphinidin 3-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC(O)=C(O)C(O)=C1 XENHPQQLDPAYIJ-PEVLUNPASA-O 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000010603 microCT Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- 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 1
- 241000554155 Andes Species 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 1
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 1
- SBBFXSBQYRSIPP-GNBUJSLZSA-O Cyanidin 3-O-arabinoside Chemical compound O[C@@H]1[C@@H](O)[C@H](CO)O[C@@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C(O)=C1 SBBFXSBQYRSIPP-GNBUJSLZSA-O 0.000 description 1
- RKWHWFONKJEUEF-GQUPQBGVSA-O Cyanidin 3-O-glucoside Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C(O)=C1 RKWHWFONKJEUEF-GQUPQBGVSA-O 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- XCTGXGVGJYACEI-BYNFETKLSA-O Delphin Natural products O([C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@H](CO)O1)c1c(-c2cc(O)c(O)c(O)c2)[o+]c2c(c(O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)cc(O)c2)c1 XCTGXGVGJYACEI-BYNFETKLSA-O 0.000 description 1
- OIZFQAFWYYKPMR-PEVLUNPASA-N Delphinidin 3-O-glucoside Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)C=1[C-](c2cc(O)c(O)c(O)c2)[O+]c2c(c(O)cc(O)c2)C=1 OIZFQAFWYYKPMR-PEVLUNPASA-N 0.000 description 1
- TWYYVOVDSNRIJM-VVFVXFQUSA-O Delphinidin 3-sambubioside Natural products O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1Oc1c(-c2cc(O)c(O)c(O)c2)[o+]c2c(c(O)cc(O)c2)c1)[C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)CO1 TWYYVOVDSNRIJM-VVFVXFQUSA-O 0.000 description 1
- SVKUZBZQDMYGEP-WOIHUOTDSA-O Delphinidin 3-sambubioside-5-glucoside Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](CO)O[C@H]1Oc1c(-c2cc(O)c(O)c(O)c2)[o+]c2c(c(O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)cc(O)c2)c1)[C@@H]1[C@H](O)[C@H](O)[C@H](O)CO1 SVKUZBZQDMYGEP-WOIHUOTDSA-O 0.000 description 1
- SVKUZBZQDMYGEP-AHKATGCTSA-O Delphinidin 5-O-beta-D-glucoside 3-O-beta-D-sambubioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C1=C2)=CC(O)=CC1=[O+]C(C=1C=C(O)C(O)=C(O)C=1)=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)CO2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 SVKUZBZQDMYGEP-AHKATGCTSA-O 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 244000207620 Euterpe oleracea Species 0.000 description 1
- 235000012601 Euterpe oleracea Nutrition 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- 101001086210 Homo sapiens Osteocalcin Proteins 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 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 1
- 244000241838 Lycium barbarum Species 0.000 description 1
- 235000015459 Lycium barbarum Nutrition 0.000 description 1
- 235000015468 Lycium chinense Nutrition 0.000 description 1
- YDIKCZBMBPOGFT-PWUSVEHZSA-N Malvidin 3-galactoside Chemical compound [Cl-].COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)=C1 YDIKCZBMBPOGFT-PWUSVEHZSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010072970 Meniscus injury Diseases 0.000 description 1
- 101150096418 Mepe gene Proteins 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 101100478063 Mus musculus Sp7 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100031475 Osteocalcin Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- VDTNZDSOEFSAIZ-HVOKISQTSA-N Peonidin 3-O-galactoside Chemical compound [Cl-].C1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)=C1 VDTNZDSOEFSAIZ-HVOKISQTSA-N 0.000 description 1
- DGLWRNZJQCODBU-IMBWBGPSSA-N Petunidin 3-arabinoside Chemical compound [Cl-].OC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@@H](O)CO2)O)=C1 DGLWRNZJQCODBU-IMBWBGPSSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 244000181957 Vaccinium atrococcum Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000003650 acai Nutrition 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 229940124605 anti-osteoporosis drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 101150067309 bmp4 gene Proteins 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000037180 bone health Effects 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 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
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- YTMNONATNXDQJF-UBNZBFALSA-N chrysanthemin Chemical compound [Cl-].O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C(O)=C1 YTMNONATNXDQJF-UBNZBFALSA-N 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000012303 cytoplasmic staining Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- AYVZVUMKUBCNQZ-UHFFFAOYSA-N delphinidin 3,5-diglucoside Natural products OCC(O)C(O)C(O)C(O)COC1=C(Oc2cc(O)cc(OCC(O)C(O)C(O)C(O)CO)c2C1)c3cc(O)c(O)c(O)c3 AYVZVUMKUBCNQZ-UHFFFAOYSA-N 0.000 description 1
- TWYYVOVDSNRIJM-AFAGGVQESA-O delphinidin 3-O-beta-D-sambubioside Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)CO1)O)O)CO)C1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC(O)=C(O)C(O)=C1 TWYYVOVDSNRIJM-AFAGGVQESA-O 0.000 description 1
- BQQCUFJAUJKCKH-GOWHUIJJSA-N delphinidin-3-O-arabinoside Chemical compound [Cl-].O[C@@H]1[C@@H](O)[C@@H](O)CO[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC(O)=C(O)C(O)=C1 BQQCUFJAUJKCKH-GOWHUIJJSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000005550 inflammation mediator Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000020094 liqueur Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- PXUQTDZNOHRWLI-OXUVVOBNSA-O malvidin 3-O-beta-D-glucoside Chemical compound COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 PXUQTDZNOHRWLI-OXUVVOBNSA-O 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- GXPTVXHTZZVLMQ-GCGJSEPQSA-N myrtillin Natural products O[C@H]1O[C@@H](OCC2=C(OC3=CC(=O)C=C(O)C3=C2)c4cc(O)c(O)c(O)c4)[C@H](O)[C@@H](O)[C@@H]1O GXPTVXHTZZVLMQ-GCGJSEPQSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000024121 nodulation Effects 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000001009 osteoporotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229930015717 petunidin Natural products 0.000 description 1
- 235000006384 petunidin Nutrition 0.000 description 1
- AFOLOMGWVXKIQL-UHFFFAOYSA-O petunidin Chemical compound OC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O)=C1 AFOLOMGWVXKIQL-UHFFFAOYSA-O 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 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
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 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)
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
-
- 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
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Botany (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
a)植物材料の粗抽出物を得るステップと、
b)前記粗抽出物を濾過するステップと、
c)前記粗抽出物を吸着剤、好ましくは樹脂、例えばポリマー樹脂、特にポリスチレン樹脂に接触させ、前記樹脂に前記アントシアニンを吸着させるステップと、
d)前記吸着剤、特に樹脂を洗浄するステップと、
e)前記吸着剤から前記アントシアニンを溶出して、アントシアニンが富化された組成物を得るステップと、
によって得ることができる。
実施例:
Delphinol(登録商標)(maquisupreme(登録商標)という商標名もある)は、Anklam Extrakt社(ドイツ)によってGMP条件下で製造される、マキベリーの高水溶性粉末状抽出物である。Delphinol(登録商標)は、最小限25%のデルフィニジンと最小限35%の総アントシアニン(前出)とを含むように規格化されている。
実施例1:
骨芽細胞の分化および機能に対するDelphinol(登録商標)の効果
in vitroでMC3T3‐E1骨芽細胞にDelphinol(登録商標)を用いることによって、この抽出物が多層増殖を刺激し、それによって、培養物のアリザリンレッドS染色(図1、左パネル)によって用量依存的に検出されるミネラル沈着の著しい増加をもたらすことを明らかにすることができた。骨結節形成の過程で、Delphinol(登録商標)は、骨芽細胞マーカー酵素ALPの活性を著しく刺激した(図1、右パネル)。
実施例2:
さらにDelphinol(登録商標)は、破骨細胞分化特異的遺伝子、すなわち骨形成タンパク質(Bmp)2、Bmp4、Runx2およびOsx、骨の恒常性を制御することが知られている2つの骨特異的転写因子、骨の細胞外マトリックスであり組織の石灰化に重要な役割を果たしていることが公知のマトリックス細胞外リン糖タンパク質(Mepe)および、骨γ‐カルボキシグルタミン酸タンパク質(骨glaタンパク質)としても知られ、骨形成のマーカーでもあるオステオカルシン(Ocn)(図2)をアップレギュレートした。
実施例3:
2つのin vivoマウスモデルにおける、骨量減少に対するDelphinol(登録商標)の経口投与の保護作用およびタンパク同化作用
骨の形成および骨芽細胞の石灰化についてのin vitro所見をin vivoアプローチで検証するために、2つの骨減少症マウスモデル、すなわち卵巣切除(OVX)誘発およびsRANKL誘発骨量減少モデルを行い、ASBMR Histomorphometry Nomenclature Committee(Dempsterら(2013年),https://www.ncbi.nlm.nih.gov/pubmed/23197339)の方法に従ってマイクロCTスキャンを用いて大腿骨構造の解析を行った。
実施例4:
マイクロCTスキャンから作成した大腿骨遠位部の3次元の矢状中央部は、Delphinol(登録商標)投与群で観察された海綿骨が、媒体群または偽群マウスの海綿骨よりも厚いことを明らかにし、これは、Delphinol(登録商標)が、破骨細胞数の著しい減少(N.Oc/BS)、高い骨量(BV/TV)および浸食の少ない表面(ES/BS)に見られるように、骨吸収を抑制するだけでなく、in vitroの所見と矛盾することなく骨形成(BFR/TV)および類骨量(OV/TV)を加速させることができることも示唆した(図4)。
実施例5:
2番目の骨減少症マウスモデル用に、雌マウスを、無処置対照群、媒体群またはDelphinol(登録商標)群のいずれかにグループ化した。後者の群にはDelphinol(登録商標)0.75mgをそれぞれ21日間投与した。7日目および8日目に、媒体群およびDelphinol(登録商標)群の腹腔内にsRANKLを注入した。OVXモデルと同様に、骨微細構造に関する後の試験のために、16日目と19日目に、2種類の蛍光分子、テトラサイクリン(TC)およびカルセイン(CAL)を注入した(図5)。
実施例6:
マイクロCTスキャンから作成した大腿骨遠位部の3次元の矢状中央部は、Delphinol(登録商標)投与群で観察された海綿骨が、媒体群または無処置対照群マウスの海綿骨よりも厚いことを明らかにし、これは、Delphinol(登録商標)が、破骨細胞数の著しい減少(N.Oc/BS)、より増加した骨量(BV/TV)およびより浸食の減少した表面(ES/BS)に見られるように、骨減少症を抑制するだけでなく、in vitroの所見と矛盾することなく骨形成(BFR/TV)および類骨量(OV/TV)を刺激することができることも示唆した(図6)。
実施例7:
NF‐κB炎症経路に対するDelphinol(登録商標)の効果
NF‐κBは、幅広い種類の免疫受容体と相互作用し、酸化ストレスによっても刺激を受ける場合がある、周知であり重点的に検査される主要な炎症メディエーターである。ひとたび活性化されれば、NF‐κBは、今度は、細胞質から核に移動し、(たとえばサイトカインおよびケモカインをコードする)多数の炎症誘発性遺伝子の発現を誘導し、これにより炎症性疾患の病原性プロセスの一因となる場合がある(図7)。
実施例8:
NF‐κB活性サブユニットp65の核内移行に対するDelphinol(登録商標)の影響の試験は、Delphinol(登録商標)が、p65サブユニットの細胞核へのLPS誘発移動をほぼ完全に抑制したことを明らかにした。これは、MC3T3‐E1骨芽細胞の細胞質染色(図8)によって明確に示される。LPS(細菌化合物)を用いて細胞を免疫刺激した。LPSが強い酸化ストレスを誘発してNF‐κB炎症性シグナル伝達カスケードを活性化させることは公知である。
Claims (10)
- 先天性骨欠損、骨変形、脊椎変形、骨肉腫、骨形成異常症、骨軟化症(くる病)、骨形成不全症(脆弱骨疾患)、パジェット病、変形性関節症の群から選択される骨損傷、骨疾患または骨欠損の治療または予防に使用するための、マキベリー抽出物を含む医薬または栄養補給剤。
- 前記骨損傷が、骨折であるか、または骨折によって生じる骨欠乏である、請求項1に記載の骨損傷の治療に使用するための医薬または栄養補給剤。
- 前記マキベリー抽出物が、特に40:60(v/v)~60:40(v/v)、特に41:59(v/v)または50:50(v/v)の水/アルコール抽出剤によって得られる、請求項1または2に記載の使用のための医薬または栄養補給剤。
- 前記アルコール抽出剤が、エタノール、特に96%エタノールである、請求項3に記載の使用のための医薬または栄養補給剤。
- 前記マキベリー抽出物が、最小限25%(w/w)のデルフィニジンと最小限35%(w/w)のアントシアニンとを含む、請求項1~4のいずれか一項に記載の使用のための医薬または栄養補給剤。
- 前記マキベリー抽出物が、最小限25%(w/w)のデルフィニジンと最小限35%(w/w)のアントシアニンとを含み、前記抽出物が、
a)植物材料の粗抽出物を得るステップと、
b)前記粗抽出物を濾過するステップと、
c)前記粗抽出物を吸着剤と接触させ、前記吸着剤、特に樹脂に前記アントシアニンを吸着させるステップと、
d)前記吸着剤を洗浄するステップと、
e)前記吸着剤から前記アントシアニンを溶出して、アントシアニンが富化された組成物を得るステップと、
によって得られる、請求項1~5のいずれか一項に記載の使用のための医薬または栄養補給剤。 - ステップd.)で水を使用し、ステップe.)でエタノールを使用する、請求項6に記載の使用のための医薬または栄養補給剤。
- ステップa.)の植物材料が、果物および/またはベリーから選択される、請求項6に記載の使用のための医薬または栄養補給剤。
- ステップc.)からステップd.)までの前記吸着剤が、樹脂、特にポリマー樹脂またはポリスチレン樹脂である、請求項6に記載の使用のための医薬または栄養補給剤。
- 適切な場合には、特に糖衣錠、錠剤、フィルムコーティング錠、粉末剤、カプセルまたは希釈液の形態での適切な担体物質、特に滴剤、ジュースまたはシロップ、軟膏、乳剤、粒状剤、粉末剤、点鼻スプレー、液体または固体の吸入製剤、圧迫包帯、創傷および歯肉の被覆、タンポナーデ、扁桃塗布液、うがい液、リンス液、注射剤、輸液、顆粒、腸溶錠、トローチ、懸濁液、湿布、点鼻薬、吸入剤、ローション、座剤、経腸栄養剤を含む製剤を含む、請求項1~9のいずれか一項に記載の使用のための医薬または栄養補給剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP19159847.3A EP3701960A1 (en) | 2019-02-27 | 2019-02-27 | Maqui berry extracts for use in the treatment or prevention of bone disorders |
EP19159847.3 | 2019-02-27 | ||
PCT/EP2020/054951 WO2020173968A1 (en) | 2019-02-27 | 2020-02-25 | Maqui berry extracts for use in the treatment or prevention of bone disorders |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2022522707A true JP2022522707A (ja) | 2022-04-20 |
Family
ID=65635475
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021550158A Pending JP2022522707A (ja) | 2019-02-27 | 2020-02-25 | 骨障害の治療または予防に使用するためのマキベリー抽出物 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20220143117A1 (ja) |
EP (2) | EP3701960A1 (ja) |
JP (1) | JP2022522707A (ja) |
KR (1) | KR20210133987A (ja) |
WO (1) | WO2020173968A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115444843B (zh) * | 2022-08-11 | 2024-02-06 | 甘肃中医药大学 | 花青素在制备保护BMSCs生物学稳定性药物中的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004507582A (ja) * | 2000-08-31 | 2004-03-11 | ハウザー、インコーポレイテッド | アントシアニンに富む組成物の有効な製法 |
JP2009167174A (ja) * | 2007-12-17 | 2009-07-30 | Nippon Seiyaku Kogyo Kk | 吸収性骨疾患の予防・治療剤 |
JP2013508347A (ja) * | 2009-10-21 | 2013-03-07 | マクイ ニュー ライフ ソシエダ アノニマ | アントシアニジンを含む組成物及び使用方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090181901A1 (en) * | 2007-11-14 | 2009-07-16 | Thomas Eidenberger | Compositions and methods to increase bioavailability of carotenoids |
EP2710901A1 (en) * | 2012-09-20 | 2014-03-26 | Symrise AG | Dietary supplement compositions |
JP2016210757A (ja) * | 2015-04-30 | 2016-12-15 | 株式会社東洋新薬 | 骨強化剤 |
-
2019
- 2019-02-27 EP EP19159847.3A patent/EP3701960A1/en not_active Withdrawn
-
2020
- 2020-02-25 EP EP20712209.4A patent/EP3930739A1/en active Pending
- 2020-02-25 WO PCT/EP2020/054951 patent/WO2020173968A1/en active Search and Examination
- 2020-02-25 JP JP2021550158A patent/JP2022522707A/ja active Pending
- 2020-02-25 KR KR1020217030341A patent/KR20210133987A/ko unknown
- 2020-02-25 US US17/433,805 patent/US20220143117A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004507582A (ja) * | 2000-08-31 | 2004-03-11 | ハウザー、インコーポレイテッド | アントシアニンに富む組成物の有効な製法 |
JP2009167174A (ja) * | 2007-12-17 | 2009-07-30 | Nippon Seiyaku Kogyo Kk | 吸収性骨疾患の予防・治療剤 |
JP2013508347A (ja) * | 2009-10-21 | 2013-03-07 | マクイ ニュー ライフ ソシエダ アノニマ | アントシアニジンを含む組成物及び使用方法 |
Non-Patent Citations (2)
Title |
---|
MINERVA CARDIOANGIOL., vol. 63(suppl.1 to No.2), JPN6023012801, 2015, pages 1 - 12, ISSN: 0005036382 * |
PLOS ONE, vol. 9(5), JPN6023012800, 2014, pages 97177 - 1, ISSN: 0005036383 * |
Also Published As
Publication number | Publication date |
---|---|
EP3930739A1 (en) | 2022-01-05 |
US20220143117A1 (en) | 2022-05-12 |
KR20210133987A (ko) | 2021-11-08 |
WO2020173968A1 (en) | 2020-09-03 |
EP3701960A1 (en) | 2020-09-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wang et al. | Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic effects | |
JP6919951B2 (ja) | 幹細胞から抽出されたエキソソームを有効成分として含む骨粗鬆症の予防または治療用の組成物 | |
CA2721566C (en) | Preparation and use of a plant extract from solanum glaucophyllum with an enriched content of 1,25-dihydroxyvitamin d3 glycosides and quercetin glycosides | |
Zhang et al. | Berberine for bone regeneration: Therapeutic potential and molecular mechanisms | |
JP2022522707A (ja) | 骨障害の治療または予防に使用するためのマキベリー抽出物 | |
KR100760384B1 (ko) | 황기 추출물을 포함하는 혈관형성 촉진 및 골유합 효과를갖는 골절의 예방 및 치료용 조성물 | |
EP3626728A1 (en) | Peptide for inhibiting bone resorption | |
EP3021844B1 (en) | Pharmaceutical composition for the treatment of diminution of bone tissue | |
KR102415187B1 (ko) | 유백피 및 산수유 복합추출물을 유효성분으로 함유하는 골질환 예방 또는 치료용 조성물 | |
KR102114378B1 (ko) | 접골공진단을 포함하는 골 관련 질환의 예방 및 치료용 조성물 | |
KR101701227B1 (ko) | 양막 및 융모막의 복합추출물을 유효성분으로 함유하는 골형성 촉진용 약학적 조성물 | |
KR102125454B1 (ko) | 겐티아나 루테아 추출물을 포함하는 골 질환 예방 또는 치료용 조성물 | |
KR101395984B1 (ko) | 레바미피드를 유효성분으로 포함하는 비만의 예방 또는 치료용 조성물 | |
KR101332824B1 (ko) | 민대극 추출물을 포함하는 관절염 예방 및 치료용 조성물 | |
KR101120499B1 (ko) | 골 질환의 예방 및 치료용 조성물 | |
KR20150081244A (ko) | 진피 추출물을 유효성분으로 함유하는 혈관신생용 약학적 조성물 | |
JP2008231080A (ja) | 脂肪細胞からのレプチン分泌促進剤 | |
KR100690500B1 (ko) | 조구등 추출물을 포함하는 혈관형성 촉진 및 골유합효과를 갖는 골절의 예방 및 치료용 조성물 | |
KR101637344B1 (ko) | 삼채뿌리 추출물을 유효성분으로 포함하는 골 성장 촉진용 조성물 | |
KR102181571B1 (ko) | 시클로피록스를 유효성분으로 포함하는 골 질환 예방 또는 치료용 조성물 | |
KR20120018556A (ko) | 마가목 및 현지초 추출물을 포함하는 파골세포 분화 억제용 또는 연골세포 분화 촉진용 조성물(sg-ⅱ) | |
KR101547732B1 (ko) | 넥탄드린 a를 유효성분으로 함유하는 골형성 촉진용 조성물 | |
KR20160149664A (ko) | 보스웰리아 세라타 추출물, 포도씨 추출물 및 주니퍼베리 추출물을 유효성분으로 함유하는 관절염의 예방, 개선 또는 치료용 조성물 | |
JP6483480B2 (ja) | 破骨細胞分化抑制剤、及び骨芽細胞分化促進剤 | |
Nguyen | Effects of nacre supplementation on bone loss (induced or natural) in rodent models |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211018 |
|
A529 | Written submission of copy of amendment under article 34 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A529 Effective date: 20211018 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220616 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230331 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230413 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230711 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230908 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231010 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240111 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20240404 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20240610 |