CN115105537A - 金骨莲制剂在制备治疗或预防肺损伤药物中的应用 - Google Patents
金骨莲制剂在制备治疗或预防肺损伤药物中的应用 Download PDFInfo
- Publication number
- CN115105537A CN115105537A CN202110305986.3A CN202110305986A CN115105537A CN 115105537 A CN115105537 A CN 115105537A CN 202110305986 A CN202110305986 A CN 202110305986A CN 115105537 A CN115105537 A CN 115105537A
- Authority
- CN
- China
- Prior art keywords
- preparation
- lung
- lung injury
- parts
- tropaeolum
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 208000004852 Lung Injury Diseases 0.000 title claims abstract description 23
- 206010069363 Traumatic lung injury Diseases 0.000 title claims abstract description 23
- 231100000515 lung injury Toxicity 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 240000002853 Nelumbo nucifera Species 0.000 title claims abstract description 10
- 235000006508 Nelumbo nucifera Nutrition 0.000 title claims abstract description 10
- 235000006510 Nelumbo pentapetala Nutrition 0.000 title claims abstract description 10
- 210000004072 lung Anatomy 0.000 claims abstract description 52
- 241000208241 Tropaeolum Species 0.000 claims abstract description 19
- 208000015181 infectious disease Diseases 0.000 claims abstract description 5
- 239000002775 capsule Substances 0.000 claims description 18
- 241000759271 Alangium Species 0.000 claims description 9
- 241001534096 Psammosilene tunicoides Species 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 206010030113 Oedema Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 210000004969 inflammatory cell Anatomy 0.000 claims description 6
- 238000010298 pulverizing process Methods 0.000 claims description 6
- 239000009910 sargent gloryvine Substances 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 230000008595 infiltration Effects 0.000 claims description 5
- 238000001764 infiltration Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 240000002381 Prunus davidiana Species 0.000 claims description 4
- 235000015533 Prunus davidiana Nutrition 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 3
- 241001533947 Psammosilene Species 0.000 claims description 3
- 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 3
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 206010046306 Upper respiratory tract infection Diseases 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 230000003902 lesion Effects 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 201000004193 respiratory failure Diseases 0.000 claims description 3
- 238000007873 sieving Methods 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010014561 Emphysema Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000009267 bronchiectasis Diseases 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 230000002458 infectious effect Effects 0.000 claims description 2
- 201000003453 lung abscess Diseases 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 210000004879 pulmonary tissue Anatomy 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims 1
- 229940124532 absorption promoter Drugs 0.000 claims 1
- -1 absorption promoters Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 206010008118 cerebral infarction Diseases 0.000 claims 1
- 239000003995 emulsifying agent Substances 0.000 claims 1
- 239000003906 humectant Substances 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- 230000000451 tissue damage Effects 0.000 claims 1
- 231100000827 tissue damage Toxicity 0.000 claims 1
- 201000008827 tuberculosis Diseases 0.000 claims 1
- 102000004889 Interleukin-6 Human genes 0.000 abstract description 16
- 108090001005 Interleukin-6 Proteins 0.000 abstract description 16
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 abstract description 13
- 101000605172 Aspergillus niger (strain CBS 513.88 / FGSC A1513) Probable endopolygalacturonase E Proteins 0.000 abstract description 13
- 101000605171 Aspergillus niger Endopolygalacturonase E Proteins 0.000 abstract description 13
- 101000941281 Bos taurus Gastric triacylglycerol lipase Proteins 0.000 abstract description 13
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 13
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 13
- 210000002966 serum Anatomy 0.000 abstract description 12
- 239000002158 endotoxin Substances 0.000 abstract description 11
- 229920006008 lipopolysaccharide Polymers 0.000 abstract description 11
- 102000003777 Interleukin-1 beta Human genes 0.000 abstract description 10
- 108090000193 Interleukin-1 beta Proteins 0.000 abstract description 10
- 206010069351 acute lung injury Diseases 0.000 abstract description 9
- 230000002829 reductive effect Effects 0.000 abstract description 5
- 230000006303 immediate early viral mRNA transcription Effects 0.000 abstract description 4
- 206010037423 Pulmonary oedema Diseases 0.000 abstract description 2
- 230000001154 acute effect Effects 0.000 abstract description 2
- 238000011160 research Methods 0.000 abstract description 2
- 208000005333 pulmonary edema Diseases 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 38
- 241000700159 Rattus Species 0.000 description 35
- 229960003957 dexamethasone Drugs 0.000 description 12
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical group C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000000589 Interleukin-1 Human genes 0.000 description 6
- 108010002352 Interleukin-1 Proteins 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 238000005303 weighing Methods 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 4
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 4
- 210000000683 abdominal cavity Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 235000007173 Abies balsamea Nutrition 0.000 description 2
- 239000004857 Balsam Substances 0.000 description 2
- 241000903210 Bryconamericus alpha Species 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 244000018716 Impatiens biflora Species 0.000 description 2
- 208000032376 Lung infection Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 2
- 101710083073 NF-kappa-B inhibitor alpha Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 2
- 229960002986 dinoprostone Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 210000003456 pulmonary alveoli Anatomy 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 208000005952 Amniotic Fluid Embolism Diseases 0.000 description 1
- 206010067010 Anaphylactoid syndrome of pregnancy Diseases 0.000 description 1
- 108010085443 Anserine Proteins 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 241000903946 Clematidis Species 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010013647 Drowning Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000003241 Fat Embolism Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000000616 Hemoptysis Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- SLRNWACWRVGMKD-UHFFFAOYSA-N L-anserine Natural products CN1C=NC(CC(NC(=O)CCN)C(O)=O)=C1 SLRNWACWRVGMKD-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 241000210053 Potentilla elegans Species 0.000 description 1
- 241000394658 Prymnesium kappa Species 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241001530121 Trollius Species 0.000 description 1
- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- MYYIAHXIVFADCU-QMMMGPOBSA-N anserine Chemical compound CN1C=NC=C1C[C@H](NC(=O)CC[NH3+])C([O-])=O MYYIAHXIVFADCU-QMMMGPOBSA-N 0.000 description 1
- 230000002924 anti-infective effect Effects 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003657 dexamethasone acetate Drugs 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000010150 least significant difference test Methods 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000000504 luminescence detection Methods 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 201000003144 pneumothorax Diseases 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002352 surface water Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/36—Caryophyllaceae (Pink family), e.g. babysbreath or soapwort
-
- 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)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明属于药物应用技术领域，具体涉及金骨莲制剂在制备治疗或预防肺损伤药物中的应用，所述金骨莲制剂由透骨香、汉桃叶、大血腾、八角枫、金铁锁制备而成，所述制剂为胶囊剂、颗粒剂、片剂、合剂、丸剂、喷雾剂等剂型。研究表明金骨莲制剂具有显著降低脂多糖致急性肺损伤大鼠血清中的TNF‑α、IL‑1β、IL‑6及PGE2表达水平，降低肺湿干重比，降低NF‑κBp65、P‑IκBα/IκBα蛋白表达水平，减轻急性感染引起的肺部水肿，可治疗或预防肺损伤。
Description
技术领域
本发明涉及药物应用技术领域，尤其是金骨莲制剂在制备治疗或预防肺损伤药物中的应用。
背景技术
肺损伤是由不同致伤因素导致的肺实质的损伤，肺部外伤、肺部手术、肺部感染、肺栓塞等都可导致肺损伤。肺损伤多是由于肺部感染、肺部手术愈合不佳引起。肺损伤的主要症状是胸痛、咯血、气促、呼吸困难、气胸、低热。
急性肺损伤(acutelunginjury，ALI)是各种因素导致的肺泡上皮细胞及毛细血管内皮细胞损伤，造成弥漫性肺间质及肺泡水肿，导致的急性低氧性呼吸功能不全，以肺容积减少、肺顺应性降低、通气/血流比例失调为病理生理特征。临床多种疾病均可引起急性肺损伤，其病因包括上呼吸道感染、肺炎、严重脓毒症、胃食管反流、大量输血、淹溺、休克、脂肪和羊水栓塞胰腺炎、肺挫伤、水杨酸盐/麻醉药过量、肺泡出血、烟雾和有毒气体吸入、再灌注损伤等疾病。
目前，国内外公认治疗ALI的方案：(1)去除病因；(2)在积极治疗原发病的基础上，尽早机械通气来纠正缺氧和改善组织供氧； (3)药物治疗；临床上广泛使用肾上腺糖皮质激素、糖皮质激素、环磷酰胺、甲胺蝶呤等治疗急性肺损伤，能减少毛细血管渗出和抑制肺纤维化的形成，使肺功能得到快速的改善；但糖皮质激素等免疫抑制剂对急性肺损伤选择性差，长期应用会产生多种并发症和副作用，严重影响患者生活质量，不适宜长期使用， 因此，寻找选择性高、毒副作用小的治疗肺损伤药物具有重要的临床意义。
金骨莲制剂，由透骨香、汉桃叶、大血腾、八角枫、金铁锁制备而成，可制成胶囊剂、颗粒剂、片剂、合剂、丸剂、喷雾剂、涂膜剂、软膏剂、贴剂等剂型。具有祛风除湿,消肿止痛。用于风湿痹阻所致的关节肿痛、屈仲不利等，金骨莲胶囊目前是已上市销售多年的治疗风湿骨痛的常用药。但在治疗或预防肺损伤的作用还未见报道。
发明内容
本发明的目的在于提供金骨莲制剂在制备治疗或预防肺损伤药物中的新用途。
本发明所述的肺损伤为感染性炎症引起的肺损伤。所述肺损伤包括上呼吸道感染、慢性支气管炎、肺气肿、慢性阻塞性肺疾病、哮喘、支气管扩张症、呼吸衰竭、肺炎、肺脓肿、肺结核、心脑缺血以及器官移植引起的肺组织损伤、炎症和感染。其主要症状为：肺组织水肿、肺泡间隔病变、炎症细胞浸润。
本发明所述金骨莲制剂，按重量份计，制成该制剂的有效组分为：透骨香170-500份、汉桃叶200-600份、大血藤180-550份、八角枫25-75份、金铁锁25-75份。
优选地，所述金骨莲制剂的有效组分为：透骨香343克、汉桃叶400克、大血 藤370克、八角枫50克、金铁锁50克。
本发明所述金骨莲制剂，是按一定工艺制备而成，其制备方法属于现有技术，可以从现有专利公开的文件中获得，或根据国家药品标准制备。如CN 03117137.0、WS-10093(ZD-0093)-2002-2012Z等。
优选为：取金铁锁加水煎煮3小时，滤过，滤液备用；药渣干燥后粉碎成细粉，备用；再将透骨香、汉桃叶、大血藤、八角枫四味，加水煎煮三次，每次2小时，合并煎液，滤过，合并上述金铁锁滤液，浓缩成清膏;加入一种或多种药学上可接受的辅料，制备成所需要的剂型。
所述金骨莲制剂加入的可接受辅料为稀释剂、助溶剂、缓释剂、吸收促进剂、崩解剂、湿润剂、粘合剂、表面活性剂，按照药学领域的常规方法，制备成所需要的剂型。
所述金骨莲制剂的剂型为胶囊剂、颗粒剂、片剂、合剂、丸剂、喷雾剂等剂型。优选为胶囊剂。
本发明所述的金骨莲制剂在使用时根据病人的情况确定用法用量。如已上市的由贵州益佰制药股份有限公司的金骨莲胶囊，规格：每粒装0.25g，用法用量: 口服。 一次 2粒，一日3次；或遵医嘱。
为了探究金骨莲制剂治疗肺损伤的用途，本发明进行了药效学研究，比较给药后大鼠血清中的TNF-α、IL-1β、IL-6及PGE2表达水平、肺湿干重比等指标变化。经动物实验验证，结果显示本发明所述的金骨莲制剂具有显著降低脂多糖致急性肺损伤大鼠血清中的TNF-α、IL-1β、IL-6及PGE2表达水平，降低肺湿干重比，降低NF-κBp65、P-IκBα/IκBα蛋白表达水平，表明其具有治疗或预防肺损伤的作用。
附图说明：
1.图1为各组大鼠肺组织观察结果（HE染色，×400）
2.图2为各组对大鼠血清TNF-α分泌的影响(ng/L，±SD，n = 8)
3.图3为各组对大鼠血清IL-1β分泌的影响(ng/L，±SD，n = 8)
4.图4为各组对大鼠血清IL-6分泌的影响(ng/L，±SD，n = 8)
5.图5为各组对大鼠血清PGE2分泌的影响(ng/L，±SD，n = 8)
6.图6为各组对大鼠肺组织湿干比的影响(mg/g，±SD，n = 8)
7.图7为各组肺组织TNF-α的mRNA表达水平（±SD，n = 3）
8.图8为各组肺组织IL-6的mRNA表达水平（±SD，n = 3）
9.图9为各组肺组织GE2的mRNA表达水平（±SD，n = 3）
10.图10为各组肺组织IL-1β的mRNA表达水平（±SD，n = 3）
11.图11为各组肺组织NF-κBp65的蛋白表达水平（±SD，n = 3）
12.图12为各组肺组织P-IκBα/IκBα的蛋白表达水平（±SD，n = 3）
13.图13为各组肺组织NF-κBp65、P-IκBα/IκBα的蛋白表达水平(±SD,n = 3)
14.图1中A为空白对照组，B为模型对照组，C为地塞米松组，D为金骨莲低剂量组，E为金骨莲中剂量组，F为金骨莲高剂量组
15.图2--图13中Con：空白对照组， Mod：模型对照组，J-L：金骨莲低剂量组，J-M：金骨莲中剂量组，J-H：金骨莲高剂量组，Dex：地塞米松组
16.与模型对照组比较，*P＜0.05，**P＜0.01，***P＜0.001。
具体实施方式
下面结合具体的实施方式来对本发明的技术方案做进一步的限定，但要求保护的范围不仅局限于所作的描述。
实验例一：金骨莲胶囊对脂多糖诱导的大鼠急性肺损伤保护作用研究
一、试验材料
1、 药品与试剂：
金骨莲胶囊（清膏）；LPS（大肠杆菌血清型O55：B5，Sigma公司）；醋酸地塞米松（规格：0.75 mg，批号：171007）；TNF-α、IL-6、IL-1β以及PGE2试剂盒（南京建成生物技术有限公司，批号：20191111）；Trizol（TAKARA，批号：9109）；iScript cDNA Synthesis Kit（Bio-Rad，批号：1708890）；iTaqTM universal SYBR Green Supermix（Bio-Rad，批号：1725124）；PierceTM Rapid Gold BCA Protein Assay Kit（Elabscience，批号：E-BC-K318-M）；5×蛋白上样缓冲液（Siwega，批号：8190011128）；TRIS（BioFROxx，批号：115KG001-1KG）；甘氨酸（BioFROxx，批号：1275KG2P5-2.5KG）；SDS（Solarbio，批号：#S8010-500g）；ECL化学发光底物（Bio-Rad，批号：170-5060）。
2、 动物 健康SD雄性大鼠，体重为（300±20）g，由长沙天勤生物技术有限公司提供（SCXK(湘)2014-0011），实验室级别SPF级。
二、试验方法：
1 造模、分组与给药
将48只雄性SD大鼠随机分为6组（n =8）,分别为空白对照组、模型对照组、金骨莲胶囊低、中、高剂量组（0.66 g×kg-1 、1.32 g×kg-1 、2.64 g×kg-1）、地塞米松组（0.945mg×kg-1）。给药组大鼠灌胃给与相应药物，空白对照组和模型对照组对应给与等体积空白溶媒，每12 h给药1次，预先连续给药3天。于末次给药后30 min除空白对照组外各组腹腔注射LPS（10 mg×kg-1），空白对照组腹腔注射等体积生理盐水，腹腔注射，6 h后出模。
测定细胞因子
尾静脉取血，室温自然凝固20分钟，3000 rpm离心20 min，分离血清，-20℃分装保存。用酶联免疫法（ELISA ）根据制造商的方法测定各组大鼠血清中TNF-α、IL-1β、 IL-6以及PGE2的含量。
肺湿重/干重(W/D)测定
取大鼠右肺中下叶，滤纸吸干表面水分后称重，为湿重（W）。然后将肺组织放置于80℃恒温干燥箱烘烤48 h后称重，为干重（D）。计算肺组织湿重干重(W/D)比值以反映肺组织的水肿程度。
肺病理学检测
取下大鼠左肺，以10 %甲醛固定，常规脱水、石蜡包埋、切片后，苏木精-伊红（HE）染色，在光学显微镜下观察大鼠肺泡间隔病变、炎症细胞浸润等肺组织病理学变化。
检测肺组织TNF-α、IL-1β、IL-6、及PGE2的表达
将大鼠肺组织RNA提取后，逆转为eDNA进行 RT-PCR检测，引物由北京擎科生物科技有限公司合成。引物如下：TNF-α引物：forward 5-'GGGGGCCACCACGCTCTTCTGTC-3'，reverse 5-' GCTGCTCCTCCGCTTGG TGGTTT -3'，IL-1β引物：forward 5-'CAGCTTTCGACAGTGAGG AGA-3'，reverse 5-'TTGTCGAGATGCTGCTGTGA-3'，IL-6引物：forward 5-'GTTTCTCTCCGCAA GAGACTTC-3'，reverse 5-'TGTGGGTGGTATCCTCTGT GA-3'，PGE2引物：forward 5-'CCCTGCCTTTCACAATCTTTGC-3'，reverse 5-'CCGACAACAGAGG ACTGAGC-3'，反应程序：95℃变性15s，60℃退伙15s，72℃延伸15s，循环数45个。3次独立重复实验。
检测肺组织NF-κBp65、IκBα、p-IκBα蛋白表达
利用蛋白质印迹法评估NF-κBp65、IκBα、p-IκBα蛋白表达水平。各组大鼠肺组织部分剪碎后加入蛋白提取试剂，提取蛋白质，利用组织匀浆仪制备组织匀浆，放冰上裂解30min，离心取上清为蛋白样，蛋白跑胶上样，经过电泳转膜封闭后，将封闭后的PVDF膜装入杂交袋中4°C孵育过夜，TBST洗脱后敷二抗。滴加新鲜配制的ECL混合溶液到膜的蛋白面侧，发光检测，用AlphaEaseFC软件处理系统分析目标带的光密度值。
统计学处理
采用SPSS 18.0软件进行统计学分析，所有数据均以±SD表示，采用单因素方差分析进行多组间样本均数比较，组间的两两比较采用LSD检验，P <0.05表示差异有统计学意义。
三、试验结果
1、肺病理学检测结果
选用HE染色方法评价肺组织的形态学改变。图1A为空白对照组大鼠肺组织病理切片, 肺泡结构清晰，肺泡壁薄，肺间质无炎症细胞浸润；图1B为模型对照组肺组织病理切片，肺间质和肺泡内水肿伴不等量的红细胞渗出和纤维素沉积，大量炎症细胞浸润，肺泡间隔增厚，成纤维细胞增生；图1C、图1D、图1E、图1F、分别为地塞米松组、金骨莲低、中、高剂量组肺组织病理切片，病理显示肺泡壁毛细血管均有轻度扩张，肺泡腔大小、形态、数量及分布未见异常，局部伴少量炎细胞浸润，间质血管轻度扩张充血，局部肺泡间隔轻度增厚，四组肺组织病理切片病变程度不同减轻。
、ELISA测定细胞因子结果
空白对照组大鼠进行腹腔注射生理盐水后，精神状态良好，行动自如，进食正常；其余各组大鼠注射LPS后出现精神不振、反应迟钝、腹泻等现象。取各组大鼠血清应用ELISA法测定TNF-α、IL-1β、IL-6以及PGE2水平，模型对照组与空白对照组比较，模型对照组大鼠血清中TNF-α、IL-1β、IL-6以及PGE2的含量均升高（P<0.01），提示LPS提高了大鼠血清中炎症细胞因子的表达，表明模型制备成功。与模型对照组比较，金骨莲中剂量组和高剂量组及地塞米松组大鼠血清中TNF-α、 IL-1β、 IL-6以及PGE2的含量均显著性降低（P<0.05），提示金骨莲中剂量组、高剂量组及地塞米松组可以有效地降低由LPS所致的炎性细胞因子的表达。结果见图2—图5。
、肺湿重/干重(W/D)测定结果
模型对照组与空白对照组比较，模型对照组大鼠肺组织W/D比值显著性升高（P <0.01），提示模型对照组大鼠肺组织出现了明显的水肿现象。金骨莲各剂量组、地塞米松组与模型对照组比较，金骨莲低、中剂量组W/D比值降低，但不具有统计学意义。金骨莲高剂量组及地塞米松组的肺组织W/D比值显著性降低（P <0.05），提示金骨莲胶囊高剂量组及地塞米松能够有效地降低由LPS所致的肺组织水肿。结果见图6。
、 RT-PCR检测肺组织TNF-α、IL-6、PGE2及IL-1β的表达结果
模型对照组与空白对照组比较，模型对照组大鼠肺组织TNF-α、IL-6、PGE2及IL-1βmRNA均显著性升高（P <0.05），提示模型对照组大鼠肺组织出现了明显的炎症反应。金骨莲各剂量组、地塞米松组与模型对照组比较，金骨莲中剂量组和地塞米松组TNF-α、IL-6、PGE2及IL-1β mRNA表达水平均降低（P <0.05）。提示金金骨莲中剂量组及地塞米松组能够有效地降低由LPS所致的肺组织炎症反应。结果见图7-图10。
、 WB检测肺组织NF-κBp65、IκBα、p-IκBα蛋白表达结果
模型组大鼠肺组织NF-κBp65、P-IκBα/IκBα蛋白水平明显高于空白对照组（P <0.01）；金骨莲各剂量组、地塞米松组与模型对照组比较，金骨莲中剂量组、高剂量组和地塞米松组大鼠肺组织NF-κBp65、P-IκBα/IκBα明显低于模型组（P <0.05）。结果见图11-图13。
四、结论：
本研究发现金骨莲胶囊可抑制大鼠肺组织中TNF-α、IL-1β、IL-6、及PGE2的表达，可以减轻LPS诱导的大鼠炎症反应，具有较好的抗感染性炎症作用，表明金骨莲胶囊能减轻肺损伤，治疗或预防肺损伤。其作用机制可能与抑制NF-κB通路有关。
实施例二：金骨莲胶囊的制备
称取金铁锁500克，加6倍量水煎煮3小时，滤过，滤液备用；药渣干燥后粉碎成细粉，备用；再称取透骨香3430克、汉桃叶4000克、大血藤3700克、八角枫500克，加6倍量水煎煮3次，每次2小时，合并煎液，滤过，合并上述金铁锁滤液，浓缩成相对密度1.25-1.28(60℃)的清膏；加入淀粉适量，混匀，干燥，粉碎，过筛，装入胶囊，制成10000粒。
实施例三：金骨莲片的制备
称取金铁锁500克，加5倍量水煎煮3小时，滤过，滤液备用；药渣干燥后粉碎成细粉，备用；再称取透骨香3430克、汉桃叶4000克、大血藤3700克、八角枫500克，加4倍量水煎煮3次，每次2小时，合并煎液，滤过，合并上述金铁锁滤液，浓缩成相对密度1.25-1.28(60℃)的清膏；加入淀粉适量，混匀，制粒，干燥、过筛，压片，制成10000片。
在此有必要指出的是，以上实验例和实施例仅限于对本发明的技术方案做进一步的阐述和理解，不能理解为对本发明的技术方案做进一步的限定，本领域技术人员作出的非突出实质性特征和显著进步的发明创造，仍然属于本发明的保护范畴。
Claims (10)
1.金骨莲制剂在制备治疗或预防肺损伤药物中的应用。
2.如权利要求1所述的应用，其特征在于，所述肺损伤为感染性炎症引起的肺损伤。
3.如权利要求1所述的应用，其特征在于，所述肺损伤包括上呼吸道感染、慢性支气管炎、肺气肿、慢性阻塞性肺疾病、哮喘、支气管扩张症、呼吸衰竭、肺炎、肺脓肿、肺结核、心脑缺血以及器官移植引起的肺组织损伤、炎症和感染。
4.如权利要求1所述的应用，其特征在于，所述肺损伤主要症状为：肺组织水肿、肺泡间隔病变、炎症细胞浸润。
5.如权利要求1所述的应用，其特征在于，所述的金骨莲制剂由如下重量份比例的原料药制成：透骨香170-500份、汉桃叶200-600份、大血藤180-550份、八角枫25-75份、金铁锁25-75份。
6.如权利要求1所述的应用，其特征在于，所述的金骨莲制剂由如下重量份比例的原料药制成：透骨香343份、汉桃叶400份、大血藤370份、八角枫50份、金铁锁50份。
7.如权利要求1-6 任一项所述的应用，其特征在于，所述金骨莲制剂是根据需要加入药学上可接受的辅料，所述辅料为稀释剂、助溶剂、缓释剂、吸收促进剂、崩解剂、湿润剂、乳化剂、粘合剂、表面活性剂中的一种或多种，按照药学领域的常规方法，制备成所需要的剂型。
8.如权利要求7所述的应用，其特征在于，所述金骨莲制剂的剂型为胶囊剂、颗粒剂、片剂、合剂、丸剂、喷雾剂等剂型。
9.如权利要求8所述的应用，其特征在于，所述金骨莲制剂的剂型为胶囊剂。
10.如权利要求9所述的应用，其特征在于，所述金骨莲制剂的制备方法为：取金铁锁加水煎煮3小时，滤过，滤液备用；药渣干燥后粉碎成细粉，备用；再将透骨香、汉桃叶、大血藤、八角枫四味,加水煎煮3次，每次2小时，合并煎液，滤过，合并上述金铁锁滤液，浓缩成清膏；加入金铁锁细粉及适量淀粉，混匀，干燥，粉碎，过筛，装入胶囊，即得。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110305986.3A CN115105537A (zh) | 2021-03-23 | 2021-03-23 | 金骨莲制剂在制备治疗或预防肺损伤药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110305986.3A CN115105537A (zh) | 2021-03-23 | 2021-03-23 | 金骨莲制剂在制备治疗或预防肺损伤药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115105537A true CN115105537A (zh) | 2022-09-27 |
Family
ID=83323153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110305986.3A Pending CN115105537A (zh) | 2021-03-23 | 2021-03-23 | 金骨莲制剂在制备治疗或预防肺损伤药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115105537A (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105193835A (zh) * | 2015-10-26 | 2015-12-30 | 天津市南开医院 | 鹅掌楸苷及其苷元在制备防治脓毒症所致肺损伤药物中的用途 |
| CN112107609A (zh) * | 2020-11-10 | 2020-12-22 | 贵州益佰制药股份有限公司 | 金骨莲制剂在制备治疗睑板腺囊肿药物中的应用 |
-
2021
- 2021-03-23 CN CN202110305986.3A patent/CN115105537A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105193835A (zh) * | 2015-10-26 | 2015-12-30 | 天津市南开医院 | 鹅掌楸苷及其苷元在制备防治脓毒症所致肺损伤药物中的用途 |
| CN112107609A (zh) * | 2020-11-10 | 2020-12-22 | 贵州益佰制药股份有限公司 | 金骨莲制剂在制备治疗睑板腺囊肿药物中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017422167B2 (en) | Preparation of Pulsatilla saponin B4 for injection | |
| WO2021179828A1 (zh) | 一种药物组合物在制备治疗急性肺损伤药物中的应用 | |
| CN114588169A (zh) | 一种贝母属异甾体生物碱单体的用途 | |
| WO2016127787A1 (zh) | 绿原酸在制备治疗心肌病的药物中的用途 | |
| CN114209810B (zh) | 枸杞糖肽在制备用于预防或治疗炎性肠病的药物中的用途 | |
| CN112641921B (zh) | 一种治疗溃疡性结肠炎的蜚蠊多肽有效部位及其制备方法和用途 | |
| Yi et al. | Intervention effects of lotus leaf flavonoids on gastric mucosal lesions in mice infected with Helicobacter pylori | |
| CN106963803B (zh) | 绞股蓝总黄酮在制备防治心肌肥厚的药物中的应用 | |
| CN115105537A (zh) | 金骨莲制剂在制备治疗或预防肺损伤药物中的应用 | |
| CN111329950A (zh) | 中药组合物及其制剂在制备治疗急性肺损伤的药物中的用途 | |
| CN1943707A (zh) | 一种用于抗衰老的中药组合物及其制备方法 | |
| CN1256949C (zh) | 三七总皂苷脂质体及其制备方法 | |
| CN113368209B (zh) | 一种芪蛭胶囊在制备治疗原发性高血压药物中的新用途 | |
| CN109512962B (zh) | 一种用于器脏纤维化的中药组合物及其制备方法和应用 | |
| CN112315971A (zh) | 一种黄芪多糖在制备治疗肾损伤药物中的应用 | |
| CN111840331A (zh) | 一种熊胆外泌体在制备治疗ii型糖尿病药物中的应用 | |
| CN114306350B (zh) | 胆固醇硫酸盐在制备预防脓毒症的药物中的用途 | |
| CN114767810B (zh) | 一种治疗急性肺损伤的中药组合物及制备方法和应用 | |
| CN115624560B (zh) | 一种治疗慢性肾功能衰竭的中药有效成分复方及其应用 | |
| CN114377030B (zh) | 一种菊苣酸与松果菊苷的药物组合物及其用途 | |
| KR100352148B1 (ko) | 베타-시토스테롤을 포함하는 혈관형성 촉진 및 관절염예방 및 치료용 조성물 | |
| CN114903951A (zh) | 龙血竭抑制肺、肝、肾纤维化的制备及应用 | |
| KR20070088940A (ko) | 우슬 추출물을 함유하는 염증성 질환의 치료 및 예방에유용한 약제 | |
| TW202410913A (zh) | 毛木耳多醣體萃取物及其用於製備促進傷口癒合之醫藥組成物的用途 | |
| CN115813988A (zh) | 一种中药制剂组合物及其制备方法、应用 |
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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Dou Qiling Inventor after: Pu Jian Inventor after: Huang Yong Inventor after: Zheng Lin Inventor after: Li Yongjun Inventor after: Tan Dan Inventor before: Dou Qiling Inventor before: Pu Jian Inventor before: Huang Yong Inventor before: Zheng Lin Inventor before: Li Yongjun Inventor before: Tan Dan |