CN114269358A - 针对纤维化、炎症、和/或老化疾病的治疗药物 - Google Patents
针对纤维化、炎症、和/或老化疾病的治疗药物 Download PDFInfo
- Publication number
- CN114269358A CN114269358A CN201980096325.5A CN201980096325A CN114269358A CN 114269358 A CN114269358 A CN 114269358A CN 201980096325 A CN201980096325 A CN 201980096325A CN 114269358 A CN114269358 A CN 114269358A
- Authority
- CN
- China
- Prior art keywords
- therapeutic
- disease
- prophylactic agent
- diseases
- agent 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
- 201000010099 disease Diseases 0.000 title claims abstract description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 68
- 230000003176 fibrotic effect Effects 0.000 title claims abstract description 22
- 230000032683 aging Effects 0.000 title claims abstract description 19
- 239000003814 drug Substances 0.000 title abstract description 8
- 229940124597 therapeutic agent Drugs 0.000 title abstract description 4
- 230000002757 inflammatory effect Effects 0.000 title description 3
- 210000001808 exosome Anatomy 0.000 claims abstract description 47
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 35
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 35
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims abstract description 22
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 17
- 208000005069 pulmonary fibrosis Diseases 0.000 claims abstract description 15
- 210000004027 cell Anatomy 0.000 claims description 27
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 13
- 210000004072 lung Anatomy 0.000 claims description 10
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 210000001185 bone marrow Anatomy 0.000 claims description 5
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 4
- 208000027932 Collagen disease Diseases 0.000 claims description 3
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 3
- 206010037765 Radiation pneumonitis Diseases 0.000 claims description 3
- 210000000577 adipose tissue Anatomy 0.000 claims description 3
- 210000004700 fetal blood Anatomy 0.000 claims description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
- 210000005259 peripheral blood Anatomy 0.000 claims description 3
- 239000011886 peripheral blood Substances 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 3
- 208000032843 Hemorrhage Diseases 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 18
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 12
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 9
- 239000002609 medium Substances 0.000 description 8
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 108010006654 Bleomycin Proteins 0.000 description 7
- 229960001561 bleomycin Drugs 0.000 description 7
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 206010016654 Fibrosis Diseases 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 230000004761 fibrosis Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 229960003073 pirfenidone Drugs 0.000 description 6
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- -1 proteins Chemical class 0.000 description 5
- 230000000391 smoking effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 210000000651 myofibroblast Anatomy 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 238000005199 ultracentrifugation Methods 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 206010014561 Emphysema Diseases 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000208125 Nicotiana Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000621 bronchi Anatomy 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 102000046949 human MSC Human genes 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 210000003456 pulmonary alveoli Anatomy 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
- 102000004008 5'-Nucleotidase Human genes 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 206010069002 Autoimmune pancreatitis Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000001267 GSK3 Human genes 0.000 description 1
- 108060006662 GSK3 Proteins 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000648544 Homo sapiens Sushi domain-containing protein 2 Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 102100025304 Integrin beta-1 Human genes 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000001705 Mouth breathing Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028594 Myocardial fibrosis Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 206010033649 Pancreatitis chronic Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 description 1
- 102100028854 Sushi domain-containing protein 2 Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010067269 Uterine fibrosis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000032677 cell aging Effects 0.000 description 1
- 230000008568 cell cell communication Effects 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 208000013116 chronic cough Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000010048 endomyocardial fibrosis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004503 fine granule Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- HLUCICHZHWJHLL-UHFFFAOYSA-N hematein Chemical compound C12=CC=C(O)C(O)=C2OCC2(O)C1=C1C=C(O)C(=O)C=C1C2 HLUCICHZHWJHLL-UHFFFAOYSA-N 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
- 229960004378 nintedanib Drugs 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000011903 nutritional therapy Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000002640 oxygen therapy Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229940124733 pneumococcal vaccine Drugs 0.000 description 1
- 238000000710 polymer precipitation Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000013630 prepared media Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 201000004087 sclerosing hepatic carcinoma Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Developmental Biology & Embryology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明的问题在于，提供一种治疗剂和预防剂，其针对肺纤维化等纤维化疾病、炎症疾病、和/或老化疾病起到了治疗效果。本发明人等着眼于外泌体而针对肺纤维化等纤维化疾病、炎症疾病、以及老化疾病的病理以及治疗方法反复进行了研究，其结果是，发现了源自间充质干细胞(MSC)的外泌体存在针对上述疾病的优异的治疗效果和/或预防效果。因此，本发明涉及一种治疗剂或预防剂以及包含该治疗和/或预防剂的医药组合物，该治疗或预防剂为纤维化疾病、炎症疾病、以及老化疾病中的至少一种疾病的治疗剂或预防剂，其包含源自间充质干细胞的外泌体。
Description
PCT国内申请，说明书已公开。
Claims (8)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2019/000152 WO2021016727A1 (zh) | 2019-07-31 | 2019-07-31 | 针对纤维化、炎症、和/或老化疾病的治疗药物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114269358A true CN114269358A (zh) | 2022-04-01 |
Family
ID=74229070
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980096325.5A Pending CN114269358A (zh) | 2019-07-31 | 2019-07-31 | 针对纤维化、炎症、和/或老化疾病的治疗药物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20220273725A1 (zh) |
| EP (1) | EP4006144A4 (zh) |
| JP (1) | JP2022542953A (zh) |
| CN (1) | CN114269358A (zh) |
| WO (1) | WO2021016727A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115475250A (zh) * | 2022-05-26 | 2022-12-16 | 南京鼓楼医院 | 一种靶向肝星状细胞并抑制其激活的载药外泌体及其制备和应用 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113521101A (zh) * | 2021-05-20 | 2021-10-22 | 广州医科大学附属第一医院（广州呼吸中心） | 干细胞来源的外泌体在制备治疗慢性阻塞性肺疾病药物中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108025027A (zh) * | 2015-06-12 | 2018-05-11 | 哈德逊医学研究中心 | 一种治疗方法 |
| CN110072534A (zh) * | 2016-10-13 | 2019-07-30 | Vbc控股有限责任公司 | 外泌体的医学应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666344B (zh) * | 2015-02-28 | 2019-09-20 | 广州医科大学附属第一医院 | 间充质干细胞外泌体在制备治疗肺纤维化的药物制剂中的应用 |
| WO2018026203A1 (ko) * | 2016-08-05 | 2018-02-08 | 한양대학교 에리카산학협력단 | 지방 유래 줄기세포로부터 추출된 엑소좀을 유효성분으로 포함하는 폐 섬유증 예방 또는 치료용 조성물 |
| KR20200040818A (ko) * | 2017-08-15 | 2020-04-20 | 칠드런'즈 메디컬 센터 코포레이션 | 정제된 중간엽 줄기 세포 엑소좀 및 그의 용도 |
| CN109432130A (zh) * | 2018-12-20 | 2019-03-08 | 中科广聚(北京)生物医学技术中心有限公司 | 间充质干细胞外泌体在制备预防和治疗放射性肺损伤的药物中的应用 |
-
2019
- 2019-07-31 WO PCT/CN2019/000152 patent/WO2021016727A1/zh unknown
- 2019-07-31 US US17/630,810 patent/US20220273725A1/en active Pending
- 2019-07-31 CN CN201980096325.5A patent/CN114269358A/zh active Pending
- 2019-07-31 JP JP2022506095A patent/JP2022542953A/ja active Pending
- 2019-07-31 EP EP19940120.9A patent/EP4006144A4/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108025027A (zh) * | 2015-06-12 | 2018-05-11 | 哈德逊医学研究中心 | 一种治疗方法 |
| CN110072534A (zh) * | 2016-10-13 | 2019-07-30 | Vbc控股有限责任公司 | 外泌体的医学应用 |
Non-Patent Citations (3)
| Title |
|---|
| AREZOO MOHAMMADIPOOR等: "Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease" * |
| GARETH R. WILLIS等: "Mesenchymal Stromal Cell Exosomes Ameliorate Experimental Bronchopulmonary Dysplasia and Restore Lung Function through Macrophage Immunomodulation" * |
| ZHIXIAN JIN等: "Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease" * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115475250A (zh) * | 2022-05-26 | 2022-12-16 | 南京鼓楼医院 | 一种靶向肝星状细胞并抑制其激活的载药外泌体及其制备和应用 |
| CN115475250B (zh) * | 2022-05-26 | 2024-03-26 | 南京鼓楼医院 | 一种靶向肝星状细胞并抑制其激活的载药外泌体及其制备和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20220273725A1 (en) | 2022-09-01 |
| EP4006144A4 (en) | 2023-04-05 |
| EP4006144A1 (en) | 2022-06-01 |
| WO2021016727A1 (zh) | 2021-02-04 |
| JP2022542953A (ja) | 2022-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Firinci et al. | Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma | |
| Li et al. | Mesenchymal stem cells in idiopathic pulmonary fibrosis | |
| Hayes et al. | Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury | |
| KR101830290B1 (ko) | 지방 유래 줄기세포로부터 추출된 엑소좀을 유효성분으로 포함하는 폐 섬유증 예방 또는 치료용 조성물 | |
| JP2023156490A (ja) | 幹細胞の培養及び治療のための培地、方法、細胞、及び分泌因子 | |
| JP6796143B2 (ja) | トロンビン処理幹細胞に由来するエキソソームを含む慢性肺疾患治療用組成物 | |
| US20190167587A1 (en) | Pharmaceutical composition for prevention or treatment of pulmonary disease including mesenchymal stem cell-derived artificial nanosomes | |
| WO2014126176A1 (ja) | 炎症性疾患の予防又は治療用組成物 | |
| JP6253590B2 (ja) | Ｈｍｇｂ１断片を利用した脊髄の損傷に対する新規治療法 | |
| CN114269358A (zh) | 针对纤维化、炎症、和/或老化疾病的治疗药物 | |
| JP2021098738A (ja) | 外傷性脳損傷後のバイオブリッジ形成時に発現する組成物 | |
| JP7045670B2 (ja) | 多能性幹細胞による虚血再灌流肺障害の軽減及び治療 | |
| Ahmadi et al. | Bone marrow mesenchymal stem cells modified pathological changes and immunological responses in ovalbumin-induced asthmatic rats possibly by the modulation of miRNA155 and miRNA133 | |
| WO2022242189A1 (zh) | 干细胞来源的外泌体在制备治疗慢性阻塞性肺疾病药物中的应用 | |
| Azimzadeh et al. | The immunoregulatory and neuroprotective effects of human adipose derived stem cells overexpressing IL-11 and IL-13 in the experimental autoimmune encephalomyelitis mice | |
| WO2020209304A1 (ja) | 線維化、炎症、及び／又は老化疾患に対する治療薬 | |
| Li et al. | Inhaled corticosteroids inhibit substance P receptor expression in asthmatic rat airway smooth muscle cells | |
| Deng et al. | Bone marrow-derived mesenchymal stem cells overexpressed with miR-182-5p protects against brain injury in a mouse model of cerebral ischemia | |
| AU2021245369A1 (en) | Method for treating hyperinflammation using mesenchymal lineage precursor or stem cells | |
| JP2021116263A (ja) | 肝疾患に対する治療剤 | |
| KR101776787B1 (ko) | 간세포의 재생 증대를 위한 중간엽 줄기세포의 제조방법 및 이를 이용한 간 경화 치료용 조성물 | |
| Liu et al. | Differential therapeutic activity of a cargo-free nanoparticle in eosinophilic and neutrophilic asthma mouse models | |
| WO2023008402A1 (ja) | 肺線維症治療剤 | |
| JPWO2006075776A1 (ja) | 慢性閉塞性肺疾患（ＣＯＰＤ）、嚢胞性線維症（ＣｙｓｔｉｃＦｉｂｒｏｓｉｓ）または肺高血圧症（ｐｕｌｍｏｎａｒｙｈｙｐｅｒｔｅｎｓｉｏｎ）治療剤 | |
| WO2024105629A1 (en) | Compositions comprising small extracellular vesicles derived from umbilical cord blood mononuclear cells for use in treating fibrotic diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220401 |