TW202135837A - 粒線體萃取物用於治療或/及預防腎臟損傷相關疾病之用途 - Google Patents
粒線體萃取物用於治療或/及預防腎臟損傷相關疾病之用途 Download PDFInfo
- Publication number
- TW202135837A TW202135837A TW110109766A TW110109766A TW202135837A TW 202135837 A TW202135837 A TW 202135837A TW 110109766 A TW110109766 A TW 110109766A TW 110109766 A TW110109766 A TW 110109766A TW 202135837 A TW202135837 A TW 202135837A
- Authority
- TW
- Taiwan
- Prior art keywords
- kidney
- mitochondria
- mitochondrial
- kidney injury
- cells
- Prior art date
Links
- 201000010099 disease Diseases 0.000 title claims abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 33
- 206010061481 Renal injury Diseases 0.000 title claims abstract description 32
- 208000037806 kidney injury Diseases 0.000 title claims abstract description 31
- 230000002438 mitochondrial effect Effects 0.000 title abstract description 38
- 238000011282 treatment Methods 0.000 title abstract description 16
- 239000000284 extract Substances 0.000 title abstract description 15
- 230000002265 prevention Effects 0.000 title abstract 2
- 210000003470 mitochondria Anatomy 0.000 claims description 37
- 230000006378 damage Effects 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 21
- 208000027418 Wounds and injury Diseases 0.000 claims description 9
- 208000020832 chronic kidney disease Diseases 0.000 claims description 9
- 208000014674 injury Diseases 0.000 claims description 8
- 230000006676 mitochondrial damage Effects 0.000 claims description 4
- 201000002793 renal fibrosis Diseases 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- 201000008383 nephritis Diseases 0.000 claims description 3
- 208000037978 tubular injury Diseases 0.000 claims description 3
- 230000010024 tubular injury Effects 0.000 claims description 3
- 230000006866 deterioration Effects 0.000 abstract description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 50
- 210000002919 epithelial cell Anatomy 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 22
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 20
- 210000003734 kidney Anatomy 0.000 description 19
- 210000001985 kidney epithelial cell Anatomy 0.000 description 18
- 239000006143 cell culture medium Substances 0.000 description 16
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 13
- 108010035532 Collagen Proteins 0.000 description 13
- 229920001436 collagen Polymers 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 13
- 239000012091 fetal bovine serum Substances 0.000 description 12
- 208000017169 kidney disease Diseases 0.000 description 11
- 210000000130 stem cell Anatomy 0.000 description 11
- 229940109239 creatinine Drugs 0.000 description 10
- 239000008363 phosphate buffer Substances 0.000 description 9
- 239000013049 sediment Substances 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 206010016654 Fibrosis Diseases 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000004761 fibrosis Effects 0.000 description 7
- 210000003292 kidney cell Anatomy 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000000872 buffer Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000005779 cell damage Effects 0.000 description 5
- 208000037887 cell injury Diseases 0.000 description 5
- 238000012258 culturing Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 238000003149 assay kit Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 208000037157 Azotemia Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 206010023421 Kidney fibrosis Diseases 0.000 description 2
- 206010037596 Pyelonephritis Diseases 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 230000004898 mitochondrial function Effects 0.000 description 2
- 230000002988 nephrogenic effect Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 210000002254 renal artery Anatomy 0.000 description 2
- 210000005084 renal tissue Anatomy 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 208000009852 uremia Diseases 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- VVBXXVAFSPEIJQ-CVIPOMFBSA-N [(2r)-3-[[(2r)-1-[[(2s,5r,8r,11r,12s,15s,18s,21s)-15-[3-(diaminomethylideneamino)propyl]-21-hydroxy-5-[(4-hydroxyphenyl)methyl]-4,11-dimethyl-2-(2-methylpropyl)-3,6,9,13,16,22-hexaoxo-8-propan-2-yl-10-oxa-1,4,7,14,17-pentazabicyclo[16.3.1]docosan-12-yl]am Chemical compound C([C@@H]1C(=O)N[C@@H](C(=O)O[C@H](C)[C@@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@H]2CC[C@H](O)N(C2=O)[C@@H](CC(C)C)C(=O)N1C)=O)NC(=O)[C@H](NC(=O)[C@H](O)COS(O)(=O)=O)CC(C)C)C(C)C)C1=CC=C(O)C=C1 VVBXXVAFSPEIJQ-CVIPOMFBSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 210000003663 amniotic stem cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 201000004559 cerebral degeneration Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 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
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000004991 placental stem cell Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012128 staining reagent Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/029—Separating blood components present in distinct layers in a container, not otherwise provided for
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/16—Blood plasma; Blood serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/19—Platelets; Megacaryocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1808—Epidermal growth factor [EGF] urogastrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1841—Transforming growth factor [TGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0605—Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/70—Undefined extracts
- C12N2500/80—Undefined extracts from animals
- C12N2500/84—Undefined extracts from animals from mammals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/998—Proteins not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
- C12N2502/115—Platelets, megakaryocytes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Anesthesiology (AREA)
Abstract
本發明係揭露一種粒線體萃取物用於治療或/及預防腎臟損傷相關疾病之用途，具體來說，藉由投予本發明所揭粒線體萃取物至一罹患腎臟損傷相關疾病之個體，係能夠有效地改善腎臟損傷相關疾病，並得預防腎臟損傷相關疾病之惡化。
Description
本發明係有關於粒線體萃取物之第二用途，特別係指粒線體萃取物用於治療或/及預防腎臟損傷相關疾病之用途。
按，粒線體係為存在人體細胞內之一個胞器，用以提供細胞正常運作所需要之ATP，並且，近期研究指出，細胞內粒線體數量增加及活化，將能夠提供幹細胞分化所需能量，有助於幹細胞成功分化。換言之，粒線體於人體能量代謝上扮演著十分重要之角色，舉例來說，若粒線體產生缺陷，將會造成退化性或老化相關疾病，例如腦退化、肌無力、肌肉病變等；而目前許多研究指出，氧化損傷造成之巴金森氏症或是阿茲海默症患者若能維持粒線體正常功能或是提升體內抗氧化能力，將有助於神經退化性疾病惡化。
腎臟組織受損超過3個月，以致於腎臟結構或功能無法恢復原有功能時，就被稱為慢性腎臟疾病，目前臨床治療上多以藥物治療為主，飲食及生活習慣控制為輔，然而當慢性腎臟疾病隨著病程逐漸惡化，患者面臨腎臟纖維化而逐漸喪失腎臟功能時，患者需要藉由血液透析或是腎臟移植來維持生命，這不僅對於患者來說是十分難受之過程，對於國家醫療成本也是高額之負擔。換言之，由於目前對於慢性腎臟疾病之致病機制與治療方法皆未有明確之認識，導致臨床上對於慢性腎臟疾病並無法提供有效之治療方式，是以，提供一種有效治療慢性腎臟疾病及腎臟纖維化之組合物或是方法乃為臨床醫療上之當務之急。
本發明之主要目的係在於提供一種粒線體萃取物之第二用途，其係能夠有效地改善或預防腎臟受損相關疾病，進而達到治療腎臟病或減緩腎臟病惡化之功效。
緣是，為能達成上述目的，本發明係揭露一種粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，具體來說，藉由投予一定量之粒線體萃取物至一罹患腎臟受損相關疾病之個體時，係能夠改善腎臟細胞受損之情形，進而達到腎臟受損相關疾病之治療或預防惡化的功效。
於本發明之實施例中，該腎臟損傷相關疾病係為腎臟纖維化、腎臟發炎、慢性腎臟病、急性腎臟病、腎小管損傷、腎衰竭、腎前性損傷、腎因性損傷、腎後性損傷、腎小球炎、腎盂腎炎、腎病症候群、尿毒症。
於本發明之一實施例中，該腎臟損傷相關疾病係具有粒線體受損及下列至少一病徵：蛋白尿、水腫、少尿、尿素氮過高、肌酸酐過高、尿酸異常、結石、腎絲球過濾率異常。
於本發明之另一實施例中，該粒線體係分離自一幹細胞，如脂肪幹細胞、CD34+造血幹細胞、間質幹細胞、骨隨幹細胞、臍帶幹細胞、羊膜幹細胞、羊水幹細胞、胎盤幹細胞、iPS、神經幹細胞。
於本發明之實施例中，粒線體於組合物中之劑量為5～80μg，又以粒線體於組合物中之劑量為40μg以上為佳。
本發明係提供一種粒線體萃取物之第二用途，意即藉由投予一定量之粒線體萃取物或含有其之組合物至一罹患腎臟損傷相關疾病之個體，係能夠有效地改善腎臟損傷相關疾病，並得預防腎臟損傷相關疾病之惡化。
一般來說，本發明所揭粒線體投予至個體之劑量係為5~80 μg，如5、10、15、20、25、30、40、50、60、65、70、80 μg等，其中，又以投予劑量為15~40 μg者為佳；並且，為能達到較佳之治療或改善腎臟疾病之功效，本發明所揭粒線體係能搭配其他組成份製備為一組合物，而所搭配之組成份又以具有生長因子者為佳，例如含有生長因子之血液製品、富含血小板之血漿（PRP）、血漿、血清、富含血小板纖維蛋白(Platelet-Rich Fibrin)等。
本發明所指「粒線體萃取物」，係指分離自一細胞中之粒線體，而所使用之分離技術或方法應要能維持粒線體結構及功能之完整性，依據本發明所屬技術領域者之通常知識者來說，分離技術或方法可為物理性或化學性。
本發明所指「細胞」，係指具有粒線體之細胞，如脂肪幹細胞、間質幹細胞、骨骼肌細胞、肝臟細胞、腎臟細胞、纖維母細胞、神經細胞、皮膚細胞、血球細胞等。
本發明所指「組合物」，係得為醫藥組合物、食品、機能性食品、營養補充品等，並依據種類不同得與不同組成份搭配而成者，而得具有不同劑型及不同投予方法。
本發明所指「腎臟損傷相關疾病」，係為腎臟細胞受損而引發之疾病，並且具有粒線體受損之病徵，如腎臟纖維化、腎臟發炎、腎臟病、急性腎臟病、腎小管損傷、腎衰竭、腎前性損傷、腎因性損傷、腎後性損傷、腎小球炎、腎盂腎炎、腎病症候群、尿毒症等。
以下，為能證實本發明所揭粒線體萃取物之功效，將茲舉若干實例並搭配圖式做詳細說明如後。
以下實例中所使用之粒線體係取自人體脂肪幹細胞（adipose-derived stem cell），但非限制本發明之粒線體僅能來自人體脂肪幹細胞，意即本發明之粒線體係得取自人體任何細胞。
以下實例中所使用之粒線體劑量係僅為例示，以粒線體劑量為15μg作為低劑量代表，40μg作為高劑量代表，並非用於限制本案之技術特徵，意即本案所揭粒線體於劑量為5～80μg揭能達成本發明所欲達成之功效。
實例一：培養腎臟上皮細胞株
將腎臟上皮細胞株培養於含有MEM-α Earl’s salt與5％胎牛血清之細胞培養基中，並置於37℃（含有5％二氧化碳）下進行培養，當細胞培養達到8成滿度時，移除細胞培養基並加入磷酸鹽緩衝液清洗細胞，再移除磷酸鹽緩衝液後，加入0.25％胰蛋白酶/2.21mM EDTA，反應20分鐘後，加入含有5％胎牛血清之MEM-α中和胰蛋白酶，收集懸浮之細胞，進行離心，而後對細胞進行計數，再以含5％胎牛血清之MEM-α進行稀釋至終濃度為每毫升中5x104個細胞，用以做後續繼代培養或分析之用。
實例二：粒線體萃取
將人體脂肪幹細胞培養至細胞數量為1.5x108
個細胞，以杜氏緩衝液（DPBS）沖洗細胞後移除杜氏緩衝液，再加入胰蛋白酶反應3分鐘後，加入幹細胞培養液（Keratinocyte SFM (1X)液體、bovine pituitary extract、10wt％胎牛血清）終止反應，而後，收集細胞後進行離心（600g、10分鐘），移除上清液，加入80毫升之IBC-1緩衝液（緩衝液（225mM甘露醇、75mM蔗糖、0.1mM EDTA、30 mMTris-HCl pH 7.4）至細胞中，進行均質後離心，得到之沈澱物即為粒線體（下稱粒線體沈澱物）。將粒線體沈澱物中加入1.5毫升IBC-1緩衝液及蛋白質分解酶抑制劑，並置於4℃，供以下實例使用。
實例三：腎臟上皮細胞損傷試驗（一）
將實例一所培養之腎臟上皮細胞於96孔盤中進行繼代培養，其中，每孔濃度為5x104
cells/200μL，培養8小時後移除上清液，以磷酸鹽緩衝液清洗後，於每孔加入200μL未含有5％胎牛血清之細胞培養液進行培養8小時，培養後分別給予不同濃度之過氧化氫（0.3、0.5、1、3、5、10mM）進行處理。以不同濃度之過氧化氫培養24小時後，分別移除每孔之上清液，再加入含有10％阿爾瑪藍（Alamar blue）之細胞培養液（100μL/孔），培養3-4小時後，進行螢光訊號測量（Excitation/Emission: 560/590 nm），結果如圖1A所示。
由圖1A之結果可知，腎臟上皮細胞經由不同濃度之過氧化氫處理24小時後，腎臟上皮細胞會開始有損傷之情形發生，其中，當過氧化氫濃度為1mM以上時，腎臟上皮細胞因損傷而導致死亡之情形大幅增加，具體來說，以濃度為1mM之過氧化氫處理腎臟上皮細胞24小時後，腎臟上皮細胞之存活率為81.4％；以濃度為5mM之過氧化氫處理腎臟上皮細胞24小時後，腎臟上皮細胞之存活率為31.3％；以濃度為10mM之過氧化氫處理腎臟上皮細胞24小時後，腎臟上皮細胞之存活率為24.2％。由此結果顯示，以過氧化氫處理腎臟上皮細胞確實能夠建構出腎臟上皮細胞受損及死亡之模式，並且，隨著添加過氧化氫之濃度增加，腎臟上皮細胞受損情形隨之惡化，並腎臟上皮細胞死亡數量亦隨之增加。
實例四：腎臟上皮細胞損傷試驗（二）
將實例一所培養之腎臟上皮細胞於96孔盤中進行繼代培養，其中，每孔濃度為1x104 cells/200μL，培養8小時後移除上清液，經由磷酸鹽緩衝液清洗後，於每孔加入體積為200μL未含有5％胎牛血清之細胞培養液培養8小時，而後分別給予濃度為1mM及3mM之過氧化氫處理4小時，再分別給予經不同濃度過氧化氫處理之細胞不同劑量（15μg及40μg）之粒線體沈澱物（實例二所製備）後，培養24小時，培養完後移除上清液，再加入含有10％阿爾瑪藍之細胞培養液（100μL/孔），於37℃環境下培養3-4小時後，於培養結束時進行螢光訊號測量（Excitation/Emission: 560/590 nm），結果如圖1B所示。
由圖1B之結果可知，經過氧化氫處理之腎臟上皮細胞會受到損傷而導致細胞存活率下降，而當腎臟上皮細胞已經被過氧化氫誘導受損後，再再投予一定量之粒線體沈澱物後，能夠明顯提升腎臟上皮細胞之存活率，並且，隨著投予劑量之增加，腎臟上皮細胞之存活率亦隨之增加。
由此結果可知，本發明所揭粒線體萃取物確實能夠保護腎臟上皮細胞，避免氧化或發炎反應而導致腎臟上皮細胞受損之情形發生，並且能夠修復受損之腎臟上皮細胞，有效地避免腎臟上皮細胞死亡。換言之，本發明所揭粒線體萃取物或含其之組合物確實具有能夠改善或/及預防因氧化壓力而導致之腎臟受損或腎臟疾病之功效。
實例五：腎臟上皮細胞纖維化試驗（一）
將實例一所培養之腎臟上皮細胞以含有5％胎牛血清之培養液培養於6孔盤，每孔濃度為1x105
cells/2ml，培養24小時後移除上清液，再以磷酸鹽緩衝液清洗後，於每孔加入1ml未含有5％胎牛血清之細胞培養液培養8小時，再給予不同濃度（100μg/ ml及400μg/ ml）之糖化終產物（AGEs-BSA）培養4小時，培養完成後，移除含有AGEs-BSA之細胞培養基並以磷酸鹽緩衝液進行清洗，而後於每孔加入1ml未含有5％胎牛血清之細胞培養液分別培養24及48小時，培養結束後分別收集上清液，再以水溶性膠原蛋白（soluble collagen）測定試劑盒（Sircol™ Soluble Collagen Assay Kit）進行膠原蛋白分泌檢測，結果如圖2A所示。
由圖2A之結果顯示，不論以高濃度（400μg/ ml）或低濃度（100μg/ ml）之AGEs-BSA處理腎臟上皮細胞，皆會增加腎臟上皮細胞膠原蛋白之分泌表現量，並且膠原蛋白之分泌表現量會隨著處理時間增加而提升，顯示AGEs-BSA確實會誘導腎臟上皮細胞病變且產生纖維化之情形，其即為慢性腎臟病之前期，且若膠原蛋白之分泌表現量持續增加，則會導致慢性腎臟病之發生。
實例六：腎臟上皮細胞纖維化試驗（二）
本實例之流程大體上等同於實例五，惟，不同者在於，於移除含有AGEs-BSA之細胞培養基後，於每孔中加入未含有5％胎牛血清之細胞培養液及不同劑量（15μg及40μg）之粒線體沈澱物（實例二所製備）後，分別培養24小時，培養完成後，分別收集上清液，並以水溶性膠原蛋白測定試劑盒進行膠原蛋白分泌檢測，結果如圖2B所示。
由圖2B之結果可知，投予粒線體沈澱物後係能夠降低腎臟上皮細胞內因AGEs-BSA誘導所產生之膠原蛋白分泌量，顯示本發明所揭粒線體或含有其之組合物係能夠達到有效地改善或/及預防腎臟纖維化或與之相關腎臟疾病之功效。
實例七：腎臟上皮細胞纖維化試驗（三）
本實例之流程大體上等同實例六，惟，不同者在於，將誘導腎臟上皮細胞纖維化之刺激劑由AGEs-BSA改為過氧化氫；檢測結果如圖2C所示。
由圖2C之結果可知，以過氧化氫處理腎臟上皮細胞係會誘導膠原蛋白分泌量增加，意即透過過氧化氫處理腎臟上皮細胞確實能夠建構出腎臟細胞纖維化之模式；而給予經過氧化氫處理後之腎臟上皮細胞粒線體沈澱物後，係能夠明顯降低腎臟上皮細胞內之膠原蛋白分泌量，顯示本發明所揭粒線體或含有其之組合物係能夠達到有效地改善或/及預防腎臟纖維化或與之相關腎臟疾病之功效。
實例八：腎臟上皮細胞內粒線體功能損傷試驗
將實例一所培養之腎臟上皮細胞於96孔盤中以含有5％胎牛血清之細胞培養液進行繼代培養，每孔濃度為5x104
cells/200μL，培養24小時後移除上清液，以磷酸鹽緩衝液清洗後，於每孔加入1ml未含有5％胎牛血清之細胞培養液進行培養8小時，培養後分別給予3mM過氧化氫及100μg/ ml之AGEs-BSA培養4小時後，移除含有過氧化氫或AGEs-BSA之細胞培養液，並以磷酸鹽緩衝液進行清洗，而後於每孔加入1ml未含有5％胎牛血清之細胞培養液及不同劑量（15μg及40μg）之粒線體沈澱物（實例二所製備），再分別進行培養24小時，培養完成後，以磷酸鹽緩衝液進行清洗，再加入含有10μM之JC-1染色試劑之緩衝液，於37℃下反應10分鐘，經清洗後，進行螢光訊號測量（Excitation/Emission: 488/530 nm），結果如圖3所示。
由圖3之結果可知，僅有以過氧化氫或AGEs-BSA處理之腎臟上皮細胞，其內JC-1單體（monomer）之表現增加，顯示腎臟上皮細胞內粒線體被過氧化氫或AGEs-BSA所造成之發炎環境而導致損傷；而先以過氧化氫或AGEs-BSA處理，再以不同劑量粒線體沈澱物處理之腎臟上皮細胞，其內JC-1單體之表現係明顯下降，並且隨著粒線體沈澱物之劑量增加，腎臟上皮細胞中JC-1單體之表現係隨之下降。
實例九：動物試驗
取10週大的C57BL / 6小鼠，飼養於恆溫和恆濕度下及12:12小時之明暗循環環境；而小鼠腎臟損傷模式將以缺血再灌流之模式（ischemia-reperfusion，下稱I/R腎臟損傷模式）進行，步驟如下：先以腹腔注射將150 mg/Kg之苯巴比妥（phenobarbital）注射至小鼠腹部，待小鼠昏迷後於其小鼠左側腎臟位置進行手術，將左側腎臟自切口處移至外面，接著以血管夾將腎動脈流入腎臟的血管阻斷，阻斷30分鐘後移除血管夾使血流再度通過，及完成I/R腎臟損傷模式
經I/R腎臟損傷模式處理後之小鼠，以腎動脈血管注射將不同劑量之粒線體（15μg及40μg）送入腎臟，即為粒線體高劑量組及粒線體低劑量組；對照組（I/R組）則注射磷酸鹽緩衝液。各組小鼠完成其處理後，分別將腎臟移回體內並進行傷口縫合；並於各組小鼠進行後的第1天（D1）及第2天（D2）收集血液樣品，測量血清肌酸酐（Creatinine，Cr）和血液尿素氮（BUN）；接著將所抽取到的血液利進行離心，分離且收集血清，分析血清中之尿素氮及肌酸酐之含量；其中，血清肌酸酐檢測以小鼠肌酸酐分析套組（廠牌: Crystal Chem; 型號: 80350）進行分析；血清尿素氮檢測以尿素分析套組（廠牌: abcam; 型號: ab83362）進行分析。於各組小鼠移植後第7天（D7）犧牲後，對各小鼠左側腎臟進行灌流並用福爾馬林固定後，進行石蠟包埋及組織切片，再進行 H＆E染色，對染色結果根據組織學研究缺血性損傷引起之形態變化，採用Jablonski半定量標準評分腎損傷程度：0分為正常組織；1分為腎小管損傷面積小於5%；2分為腎小管損傷面積為5%以上至25%以下；3分為腎小管損傷面積為大於25%至75%以下；4分為腎小管損傷面積大於75%。
上述結果如下表1所示。由表1之結果可知，相較於控制組來說，I/R組血清中之尿素氮與肌酸酐之的表現量會有明顯的增加，顯示I/R腎臟損傷模式確實會造成腎臟損傷，並且，由腎臟損傷評分之結果可得知I/R組之分數為3-4分，代表腎小管損傷嚴重；而相較於I/R組來說，給予粒線體之組別的小鼠血清中尿素氮與肌酸酐之含量明顯降低，顯示給予粒線體係能夠有效地改善腎臟損傷，並由腎臟損傷評分之結果可知投予粒線體能夠使受損腎臟細胞恢復，改善腎小管損傷之狀況，且隨著給予粒線體劑量之增加，改善腎臟損傷之效果增加。
表1：各組小鼠經不同處理後之血清及腎臟組織切片之分析結果
| 控制組 | I/R組 | 粒線體低劑量組（15μg） | 粒線體低劑量組（40μg） | |
| D1血清中尿素氮(mg/dL) | 19±1.8 | 61±2.6 | 25±2.3 | 24±2.4 |
| D2血清中尿素氮(mg/dL) | 21±1.6 | 119±2.2 | 63±1.9 | 41±2.1 |
| D1血清中肌酸酐(mg/dL) | 0.23±0.024 | 0.41±0.021 | 0.31±0.023 | 0.29±0.025 |
| D2血清中肌酸酐(mg/dL) | 0.22±0.03 | 0.59±0.022 | 0.42±0.026 | 0.34±0.031 |
| D7腎臟損傷評分 | 0 | 3.7±0.32 | 2.9±0.29 | 1.8±0.35 |
由上述結果顯示，當腎臟細胞因纖維化、氧化壓力或是發炎環境造成粒線體受損情形發生時，投予本發明所揭粒線體萃取物或含有其之組合物，係能夠有效地改善腎臟細胞粒線體受損之情形，進而能夠達到改善或治療腎臟細胞受損或與之相關疾病之功效。
無
圖1A係為統計分析腎臟上皮細胞經不同濃度過氧化氫處理24小時後之存活率的結果。
圖1B係為統計分析腎臟上皮細胞經不同濃度過氧化氫處理後，再投予不同劑量之粒線體沈澱物後之存活率的結果。
圖2A係腎臟上皮細胞經不同濃度糖化終產物（AGEs-BSA）分別處理不同時間後，檢測分析腎臟上皮細胞膠原蛋白分泌量之結果。
圖2B係腎臟上皮細胞經不同濃度AGEs-BSA分別處理並再投予不同劑量之粒線體沈澱物後，檢測分析腎臟上皮細胞膠原蛋白分泌量之結果。
圖2C圖2B係腎臟上皮細胞經不同濃度之過氧化氫分別處理並再投予不同劑量之粒線體沈澱物後，檢測分析腎臟上皮細胞膠原蛋白分泌量之結果。
圖3係為係腎臟上皮細胞經過氧化氫或AGEs-BSA分別處理，並再投予不同劑量之粒線體沈澱物後，檢測分析腎臟上皮細胞粒線體受損情形之結果。
Claims (9)
- 一種粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎臟損傷相關疾病係為腎臟纖維化。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎臟損傷相關疾病係為腎臟發炎。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎臟損傷相關疾病係具有粒線體受損之病徵。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎臟損傷相關疾病係為慢性腎臟病。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎臟損傷相關疾病係為腎小管損傷。
- 如請求項6所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該腎小管損傷之病徵為損傷面積係大於25％。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該組合物中之該粒線體之劑量為5μg以上。
- 如請求項1所述粒線體用於製備預防或/及治療腎臟損傷相關疾病之組合物之用途，其中，該組合物中之該粒線體之劑量為40μg以上。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202062992546P | 2020-03-20 | 2020-03-20 | |
| US62/992546 | 2020-03-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202135837A true TW202135837A (zh) | 2021-10-01 |
| TWI789723B TWI789723B (zh) | 2023-01-11 |
Family
ID=77768010
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110109766A TWI789723B (zh) | 2020-03-20 | 2021-03-18 | 粒線體用於治療或/及預防腎臟損傷相關疾病之用途 |
| TW110109765A TWI787761B (zh) | 2020-03-20 | 2021-03-18 | 粒線體用於促進傷口修復及/或傷口癒合之用途 |
| TW111140519A TWI827321B (zh) | 2020-03-20 | 2021-03-18 | 含有粒線體之組合物及其用於作為膠原蛋白增生促進劑之用途 |
| TW110109767A TWI789724B (zh) | 2020-03-20 | 2021-03-18 | 粒線體用於治療及/或預防肌腱受損或其相關疾病之用途 |
| TW110109873A TWI787763B (zh) | 2020-03-20 | 2021-03-19 | 含有粒線體的組合物 |
| TW110109872A TWI849298B (zh) | 2020-03-20 | 2021-03-19 | 促進毛髮再生的富粒線體血漿、其製造方法及其用途 |
| TW110109874A TWI796653B (zh) | 2020-03-20 | 2021-03-19 | 細胞培養組合物及其用途 |
| TW113121686A TWI853788B (zh) | 2020-03-20 | 2021-03-19 | 改善發炎反應的組合物及其用途 |
Family Applications After (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110109765A TWI787761B (zh) | 2020-03-20 | 2021-03-18 | 粒線體用於促進傷口修復及/或傷口癒合之用途 |
| TW111140519A TWI827321B (zh) | 2020-03-20 | 2021-03-18 | 含有粒線體之組合物及其用於作為膠原蛋白增生促進劑之用途 |
| TW110109767A TWI789724B (zh) | 2020-03-20 | 2021-03-18 | 粒線體用於治療及/或預防肌腱受損或其相關疾病之用途 |
| TW110109873A TWI787763B (zh) | 2020-03-20 | 2021-03-19 | 含有粒線體的組合物 |
| TW110109872A TWI849298B (zh) | 2020-03-20 | 2021-03-19 | 促進毛髮再生的富粒線體血漿、其製造方法及其用途 |
| TW110109874A TWI796653B (zh) | 2020-03-20 | 2021-03-19 | 細胞培養組合物及其用途 |
| TW113121686A TWI853788B (zh) | 2020-03-20 | 2021-03-19 | 改善發炎反應的組合物及其用途 |
Country Status (6)
| Country | Link |
|---|---|
| US (6) | US20230042445A1 (zh) |
| EP (2) | EP4122474A4 (zh) |
| JP (2) | JP7563782B2 (zh) |
| CN (15) | CN117357559A (zh) |
| TW (8) | TWI789723B (zh) |
| WO (6) | WO2021185364A1 (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI789723B (zh) * | 2020-03-20 | 2023-01-11 | 台灣粒線體應用技術股份有限公司 | 粒線體用於治療或/及預防腎臟損傷相關疾病之用途 |
| WO2023221987A1 (zh) * | 2022-05-16 | 2023-11-23 | 台湾粒线体应用技术股份有限公司 | 用于减缓口腔损伤的组合物、其用途及其制备方法 |
| CN116478920A (zh) * | 2023-05-05 | 2023-07-25 | 重庆理工大学 | 一种离体线粒体的体外储存方法 |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7005274B1 (en) * | 1999-09-15 | 2006-02-28 | Migenix Corp. | Methods and compositions for diagnosing and treating arthritic disorders and regulating bone mass |
| AU2005210503B2 (en) * | 2004-02-02 | 2010-02-25 | Nestec S.A. | Genes associated with canine osteoarthritis and related methods and compositions |
| WO2009002811A2 (en) * | 2007-06-22 | 2008-12-31 | Children's Medical Center Corporation | Therapeutic platelet compositions and methods |
| US8734854B2 (en) * | 2009-07-09 | 2014-05-27 | Orogen Biosciences Inc. | Process for removing growth factors from platelets |
| US20130022666A1 (en) * | 2011-07-20 | 2013-01-24 | Anna Brzezinska | Methods and compositions for transfer of mitochondria into mammalian cells |
| WO2013035101A1 (en) * | 2011-09-11 | 2013-03-14 | Minovia Therapeutics Ltd. | Compositions of functional mitochondria and uses thereof |
| EP2591812A1 (en) * | 2011-11-14 | 2013-05-15 | University of Twente, Institute for Biomedical Technology and Technical Medicine (MIRA) | A dextran-based tissuelette containing platelet-rich plasma lysate for cartilage repair |
| US20140024677A1 (en) * | 2012-04-09 | 2014-01-23 | Musc Foundation For Research Development | Methods for inducing mitochondrial biogenesis |
| WO2013171752A1 (en) * | 2012-05-16 | 2013-11-21 | Minovia Therapeutics Ltd. | Compositions and methods for inducing angiogenesis |
| CN105163750B (zh) * | 2013-02-07 | 2022-07-15 | 李震义 | 长效人重组可溶性肿瘤坏死因子α受体在制备预防和治疗慢性肝病重症肝损伤药物中的用途 |
| US20150064715A1 (en) * | 2013-08-28 | 2015-03-05 | Musc Foundation For Research Development | Urinary biomarkers of renal and mitochondrial dysfunction |
| TW201509425A (zh) * | 2013-09-13 | 2015-03-16 | Taichung Hospital Ministry Of Health And Welfare | 以血液製備修復傷口用醫藥組合物之方法 |
| TWI672147B (zh) * | 2014-09-10 | 2019-09-21 | 台灣粒線體應用技術股份有限公司 | 以外源性粒線體爲有效成份之組合物、其用途及修復細胞之方法 |
| CN105520891B (zh) * | 2014-09-30 | 2019-05-21 | 台湾粒线体应用技术股份有限公司 | 以外源性线粒体为有效成份的组合物、其用途及修复细胞的方法 |
| US10420798B2 (en) * | 2014-12-31 | 2019-09-24 | Taiwan Mitochondrion Applied Technology Co., Ltd | Method for treating lung injury and/or diseases related to lung injury |
| CN106029102A (zh) * | 2015-01-15 | 2016-10-12 | 小威廉·K·博斯 | 使用富血小板血浆进行组织的修复和复壮 |
| CN104546915B (zh) * | 2015-02-16 | 2018-12-11 | 天晴干细胞股份有限公司 | 一种治疗骨性关节炎的组合物的制备方法 |
| IL254071B2 (en) * | 2015-02-26 | 2024-01-01 | Minovia Therapeutics Ltd | Mammalian cells are enriched in active mitochondria |
| CN105030647B (zh) * | 2015-09-14 | 2018-04-24 | 广州赛莱拉干细胞科技股份有限公司 | 一种减少皱纹的制剂及其制备方法 |
| WO2017076782A1 (en) * | 2015-11-02 | 2017-05-11 | Novahep Ab | Compositions and methods for healing wounds |
| CN105477018A (zh) * | 2015-12-07 | 2016-04-13 | 深圳爱生再生医学科技有限公司 | 修复皮肤溃疡的干细胞制剂及其制备方法 |
| JP7185527B2 (ja) | 2016-01-15 | 2022-12-07 | ザ チルドレンズ メディカル センター コーポレーション | ミトコンドリアおよび組み合わされたミトコンドリア剤の治療的使用 |
| US20170224764A1 (en) * | 2016-02-10 | 2017-08-10 | Cornell University | Therapeutic targeting of mitochondria to prevent osteoarthritis |
| TWI637748B (zh) * | 2016-07-12 | 2018-10-11 | 中山醫學大學 | 蓮蓬萃取物用於治療及／或預防腎臟病變之用途 |
| CN106190963A (zh) * | 2016-07-13 | 2016-12-07 | 浙江大学 | 一种采用线粒体移植促进损伤神经元存活的方法 |
| WO2018101708A1 (ko) * | 2016-11-30 | 2018-06-07 | 차의과학대학교 산학협력단 | 미토콘드리아를 포함하는 약학 조성물 |
| CN106822183B (zh) * | 2016-12-26 | 2020-04-14 | 中山光禾医疗科技有限公司 | 一种光敏富血小板血浆凝胶及其制备方法和用途 |
| US20200023005A1 (en) * | 2017-03-26 | 2020-01-23 | Minovia Therapeutics Ltd. | Mitochondrial compositions and methods for treatment of skin and hair |
| WO2018212758A1 (en) * | 2017-05-15 | 2018-11-22 | Miron Richard J | Liquid platelet-rich fibrin as a carrier system for biomaterials and biomolecules |
| WO2018222906A1 (en) * | 2017-06-01 | 2018-12-06 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Formation of stable cartilage |
| US20190008896A1 (en) * | 2017-07-07 | 2019-01-10 | Richard Postrel | Methods and Systems for the Prevention, Treatment and Management of Disease and Effects of Aging Via Cell-to-Cell Restoration Therapy Using Subcellular Transactions |
| CN107625969A (zh) * | 2017-10-18 | 2018-01-26 | 南京市儿童医院 | MiR‑214拮抗剂在制备用于减轻蛋白尿引起的肾小管损伤相关病症的药物中的用途 |
| WO2019083201A2 (ko) * | 2017-10-24 | 2019-05-02 | 주식회사 엑소코바이오 | 지방줄기세포 유래의 엑소좀을 유효성분으로 포함하는 조성물의 신장 기능 개선 용도 |
| KR20190052266A (ko) * | 2017-11-08 | 2019-05-16 | 원광대학교산학협력단 | 우르솔산을 유효성분으로 포함하는 신장 기능의 개선 또는 치료용 조성물 |
| EP3747449A4 (en) * | 2018-02-02 | 2021-10-20 | Paean Biotechnology Inc. | PHARMACEUTICAL COMPOSITION CONSISTING OF ISOLATED MITOCHONDRIA FOR THE PREVENTION OR TREATMENT OF RHEUMATOID ARTHRITIS |
| SG11202008839WA (en) * | 2018-03-13 | 2020-10-29 | Univ Leland Stanford Junior | Transient cellular reprogramming for reversal of cell aging |
| WO2019183042A1 (en) * | 2018-03-20 | 2019-09-26 | Unity Biotechnology, Inc. | Autologous mitochondrial extraction and expansion |
| CA3106188A1 (en) * | 2018-07-22 | 2020-01-30 | Minovia Therapeutics Ltd. | Mitochondrial augmentation therapy with stem cells enriched with functional mitochondria |
| US20210275587A1 (en) * | 2018-07-22 | 2021-09-09 | Minovia Therapeutics Ltd. | Mitochondrial augmentation therapy of renal diseases |
| EP3851112A4 (en) * | 2018-09-14 | 2022-07-27 | Luca Science Inc. | TRANSPLANTATION OF MITOCHONDRIA IN A LYMPHOID ORGAN AND ASSOCIATED COMPOSITION |
| KR102128003B1 (ko) * | 2018-10-31 | 2020-06-29 | 차의과학대학교 산학협력단 | 분리된 미토콘드리아를 포함하는 건병증 예방 또는 치료용 약학 조성물 |
| CN110055216A (zh) * | 2019-05-09 | 2019-07-26 | 张秀明 | 一种改善间质干细胞生物学功能的方法 |
| CN110638833A (zh) * | 2019-11-15 | 2020-01-03 | 西安圣德生物科技有限公司 | 促进毛发生长的组合物及其使用方法 |
| CN110812480B (zh) * | 2019-11-28 | 2021-04-02 | 中国科学院昆明动物研究所 | 一种抗菌肽和线粒体dna复合物及其多克隆抗体和应用 |
| TWI789723B (zh) * | 2020-03-20 | 2023-01-11 | 台灣粒線體應用技術股份有限公司 | 粒線體用於治療或/及預防腎臟損傷相關疾病之用途 |
-
2021
- 2021-03-18 TW TW110109766A patent/TWI789723B/zh active
- 2021-03-18 TW TW110109765A patent/TWI787761B/zh active
- 2021-03-18 TW TW111140519A patent/TWI827321B/zh active
- 2021-03-18 TW TW110109767A patent/TWI789724B/zh active
- 2021-03-19 TW TW110109873A patent/TWI787763B/zh active
- 2021-03-19 EP EP21770630.8A patent/EP4122474A4/en active Pending
- 2021-03-19 CN CN202311570784.7A patent/CN117357559A/zh active Pending
- 2021-03-19 CN CN202180014788.XA patent/CN115315265B/zh active Active
- 2021-03-19 CN CN202410555661.4A patent/CN118557603A/zh active Pending
- 2021-03-19 CN CN202410329249.0A patent/CN118319950A/zh active Pending
- 2021-03-19 JP JP2022556517A patent/JP7563782B2/ja active Active
- 2021-03-19 US US17/912,336 patent/US20230042445A1/en active Pending
- 2021-03-19 US US17/912,458 patent/US20230165899A1/en active Pending
- 2021-03-19 TW TW110109872A patent/TWI849298B/zh active
- 2021-03-19 WO PCT/CN2021/081854 patent/WO2021185364A1/zh active Application Filing
- 2021-03-19 CN CN202410555664.8A patent/CN118557604A/zh active Pending
- 2021-03-19 CN CN202180022924.XA patent/CN115335065A/zh active Pending
- 2021-03-19 TW TW110109874A patent/TWI796653B/zh active
- 2021-03-19 WO PCT/CN2021/081685 patent/WO2021185340A1/zh active Application Filing
- 2021-03-19 CN CN202410329264.5A patent/CN118319951A/zh active Pending
- 2021-03-19 CN CN202180014670.7A patent/CN115135328B/zh active Active
- 2021-03-19 WO PCT/CN2021/081686 patent/WO2021185341A1/zh active Application Filing
- 2021-03-19 TW TW113121686A patent/TWI853788B/zh active
- 2021-03-19 CN CN202311621466.9A patent/CN117379458A/zh active Pending
- 2021-03-19 US US17/912,394 patent/US20230137870A1/en active Pending
- 2021-03-19 WO PCT/CN2021/081687 patent/WO2021185342A1/zh active Application Filing
- 2021-03-19 CN CN202180014777.1A patent/CN115103683B/zh active Active
- 2021-03-19 CN CN202410555655.9A patent/CN118557602A/zh active Pending
- 2021-03-22 CN CN202180022370.3A patent/CN115315248A/zh active Pending
- 2021-03-22 WO PCT/CN2021/082094 patent/WO2021185376A1/zh active Application Filing
- 2021-03-22 CN CN202410414731.4A patent/CN118252850A/zh active Pending
- 2021-03-22 CN CN202180022422.7A patent/CN115297872B/zh active Active
- 2021-03-22 EP EP21770632.4A patent/EP4122444A4/en active Pending
- 2021-03-22 CN CN202410414725.9A patent/CN118236473A/zh active Pending
- 2021-03-22 WO PCT/CN2021/082117 patent/WO2021185377A1/zh active Application Filing
-
2022
- 2022-09-19 US US17/948,007 patent/US20230023438A1/en active Pending
- 2022-09-19 US US17/947,994 patent/US20230023218A1/en active Pending
- 2022-09-20 US US17/948,764 patent/US20230016499A1/en active Pending
-
2024
- 2024-07-12 JP JP2024112807A patent/JP2024133717A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2021185341A1 (zh) | 线粒体萃取物用于治疗或/及预防肾脏损伤相关疾病的用途 | |
| Zhou et al. | SGLT-2 inhibitors reduce glucose absorption from peritoneal dialysis solution by suppressing the activity of SGLT-2 | |
| Na et al. | Protective effects of astragaloside in rats with adriamycin nephropathy and underlying mechanism | |
| Zhang et al. | Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats | |
| CN108434139B (zh) | 缺氧诱导因子脯氨酰羟化酶活性抑制剂在制备防治急性肾损伤药物中的应用 | |
| Huan-Yu et al. | Effects of Bunao-Fuyuan decoction serum on proliferation and migration of vascular smooth muscle cells in atherosclerotic | |
| Lai et al. | Combination of PDGF-BB and adipose-derived stem cells accelerated wound healing through modulating PTEN/AKT pathway | |
| Wang et al. | Myricetin ameliorates cognitive impairment in 3× Tg Alzheimer’s disease mice by regulating oxidative stress and tau hyperphosphorylation | |
| TWI857807B (zh) | 含有粒線體之組合物及其用於作為皮膚纖維母細胞活性促進劑之用途 | |
| Gao et al. | Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway | |
| TWI818598B (zh) | 用於緩解腎臟疾病與器官纖維化的方法 | |
| US20240117316A1 (en) | Method for preparing mesenchymal stem cell-derived extracellular vesicle, mesenchymal stem cell-derived extracellular vesicle prepared by the method, and use of mesenchymal stem cell-derived extracellular vesicle for reducing adipogenesis and treating osteoarthritis | |
| TW202327568A (zh) | 藻褐素用於製備預防心臟疾病的組合物的用途 | |
| CN117701493A (zh) | 一种包含肾祖干细胞外泌体的生物制品以及其治疗肾损伤方面的应用 | |
| KR20240149593A (ko) | 글리세롤 및 포름산 대사체 측정을 통한 허혈성 뇌졸중의 예후 판단 방법 | |
| Yuan et al. | Protein expression changes in cornea after collagen crosslinking | |
| TW202327566A (zh) | 包含藻褐素及小分子褐藻醣膠之組合物用於製備治療或改善慢性腎病之醫藥品的用途及包含藻褐素、小分子褐藻醣膠及左旋肉鹼之組合物及包含其的醫藥品 | |
| Yun et al. | Salidroside improves skeletal muscle dysfunction in COPD rats by down regulating SIRT1 signaling pathway | |
| CN109771446A (zh) | 唾液链球菌k12在制备预防和/或治疗自身免疫性疾病的药物中的应用 | |
| CN118717740A (zh) | Pt2385在骨关节炎上的应用 | |
| Bittel | Functional and Skeletal Muscle Impairments In Progressive Diabetic CKD | |
| TW202112383A (zh) | 組合使用粒線體的活性抑制處理與人類瓦頓氏膠間葉幹細胞來治療粒線體dna突變關聯性疾病 | |
| Boya et al. | An investigation of Vitamin D effect on alterations of glomerular filtration rate (GFR) in patients with chronic renal failure | |
| Won et al. | Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy 2 Running title: NLRP3 mediates hyperuricemia-induced IL-1β in DM 3 | |
| Haley et al. | Investigating the Regulation of Alpha-Synuclein Clearance by Alpha-Galactosidase-A in Parkinson Disease (pp. 48-53) |