JPWO2017177966A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2017177966A5 JPWO2017177966A5 JP2018554375A JP2018554375A JPWO2017177966A5 JP WO2017177966 A5 JPWO2017177966 A5 JP WO2017177966A5 JP 2018554375 A JP2018554375 A JP 2018554375A JP 2018554375 A JP2018554375 A JP 2018554375A JP WO2017177966 A5 JPWO2017177966 A5 JP WO2017177966A5
- Authority
- JP
- Japan
- Prior art keywords
- magnesium
- inhalation
- lactose
- preparation according
- nebulizer
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 claims description 97
- 238000002360 preparation method Methods 0.000 claims description 88
- OOFIGFSMYVFBJE-WEUGGKDZSA-H trimagnesium;(2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-3,4, Chemical group [Mg+2].[Mg+2].[Mg+2].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O OOFIGFSMYVFBJE-WEUGGKDZSA-H 0.000 claims description 87
- 239000006199 nebulizer Substances 0.000 claims description 82
- 238000009472 formulation Methods 0.000 claims description 61
- 239000007788 liquid Substances 0.000 claims description 60
- 239000002245 particle Substances 0.000 claims description 59
- FYYHWMGAXLPEAU-UHFFFAOYSA-N magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 57
- 239000011777 magnesium Substances 0.000 claims description 57
- 229910052749 magnesium Inorganic materials 0.000 claims description 57
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 claims description 47
- 239000008101 lactose Substances 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 46
- 229940079593 drugs Drugs 0.000 claims description 44
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 44
- 239000011780 sodium chloride Substances 0.000 claims description 35
- 235000002639 sodium chloride Nutrition 0.000 claims description 35
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 26
- 238000009826 distribution Methods 0.000 claims description 25
- 239000002775 capsule Substances 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 229940112141 Dry Powder Inhaler Drugs 0.000 claims description 15
- 206010036790 Productive cough Diseases 0.000 claims description 15
- 239000000796 flavoring agent Substances 0.000 claims description 14
- 239000008215 water for injection Substances 0.000 claims description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000007951 isotonicity adjuster Substances 0.000 claims description 8
- 239000003002 pH adjusting agent Substances 0.000 claims description 8
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 6
- 235000013355 food flavoring agent Nutrition 0.000 claims description 6
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K Trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 4
- 238000005296 abrasive Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 235000001727 glucose Nutrition 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000001103 potassium chloride Substances 0.000 claims description 4
- 235000011164 potassium chloride Nutrition 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 239000001187 sodium carbonate Substances 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 239000011778 trisodium citrate Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N β-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 150000003904 phospholipids Chemical group 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 229960001367 tartaric acid Drugs 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 235000011054 acetic acid Nutrition 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- VMHLLURERBWHNL-UHFFFAOYSA-M sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- 239000001632 sodium acetate Substances 0.000 claims 1
- 235000017281 sodium acetate Nutrition 0.000 claims 1
- 235000019263 trisodium citrate Nutrition 0.000 claims 1
- 241000700159 Rattus Species 0.000 description 37
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 35
- 239000000243 solution Substances 0.000 description 27
- 239000000843 powder Substances 0.000 description 25
- 239000002253 acid Substances 0.000 description 23
- 210000004072 Lung Anatomy 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 150000003839 salts Chemical class 0.000 description 19
- 239000003205 fragrance Substances 0.000 description 16
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 13
- 229960003531 Phenolsulfonphthalein Drugs 0.000 description 13
- 238000000889 atomisation Methods 0.000 description 13
- 206010019799 Hepatitis viral Diseases 0.000 description 12
- 210000000265 Leukocytes Anatomy 0.000 description 12
- 210000003802 Sputum Anatomy 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000001802 infusion Methods 0.000 description 12
- 201000001862 viral hepatitis Diseases 0.000 description 12
- 210000000440 Neutrophils Anatomy 0.000 description 11
- 230000001603 reducing Effects 0.000 description 11
- 210000004969 Inflammatory Cells Anatomy 0.000 description 10
- 210000004027 cells Anatomy 0.000 description 10
- 230000001684 chronic Effects 0.000 description 10
- 238000001764 infiltration Methods 0.000 description 10
- 239000000443 aerosol Substances 0.000 description 9
- 235000019634 flavors Nutrition 0.000 description 8
- 230000001965 increased Effects 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 210000001519 tissues Anatomy 0.000 description 8
- 210000004369 Blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000010419 fine particle Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 230000036912 Bioavailability Effects 0.000 description 6
- LPLVUJXQOOQHMX-MYOOOWEVSA-N Glycyrrhizic acid Natural products O=C(O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@H](C(=O)O)O2)[C@@H](O[C@@H]2C(C)(C)[C@H]3[C@@](C)([C@H]4C(=O)C=C5[C@](C)([C@]4(C)CC3)CC[C@]3(C)[C@H]5C[C@](C(=O)O)(C)CC3)CC2)O1 LPLVUJXQOOQHMX-MYOOOWEVSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 210000003437 Trachea Anatomy 0.000 description 6
- 230000035514 bioavailability Effects 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 239000003172 expectorant agent Substances 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 230000003902 lesions Effects 0.000 description 6
- 241000202807 Glycyrrhiza Species 0.000 description 5
- 231100000494 adverse effect Toxicity 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000002354 daily Effects 0.000 description 5
- 230000003419 expectorant Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 235000019410 glycyrrhizin Nutrition 0.000 description 5
- 210000002345 respiratory system Anatomy 0.000 description 5
- 230000001954 sterilising Effects 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000001225 therapeutic Effects 0.000 description 5
- 240000002254 Ananas comosus Species 0.000 description 4
- 235000007119 Ananas comosus Nutrition 0.000 description 4
- 208000006673 Asthma Diseases 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N Carbon tetrachloride Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 4
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 4
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 4
- 229940010454 Licorice Drugs 0.000 description 4
- 235000016247 Mentha requienii Nutrition 0.000 description 4
- 235000002899 Mentha suaveolens Nutrition 0.000 description 4
- 240000008790 Musa x paradisiaca Species 0.000 description 4
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- 208000009269 Pulmonary Emphysema Diseases 0.000 description 4
- 230000001154 acute Effects 0.000 description 4
- 235000006682 bigleaf mint Nutrition 0.000 description 4
- 239000010630 cinnamon oil Substances 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 201000004624 dermatitis Diseases 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 239000001685 glycyrrhizic acid Substances 0.000 description 4
- 229960004949 glycyrrhizic acid Drugs 0.000 description 4
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 4
- 235000014063 licorice root Nutrition 0.000 description 4
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 4
- 239000001683 mentha spicata herb oil Substances 0.000 description 4
- 235000006679 mint Nutrition 0.000 description 4
- 239000007968 orange flavor Substances 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 235000019477 peppermint oil Nutrition 0.000 description 4
- 230000000275 pharmacokinetic Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000779 smoke Substances 0.000 description 4
- 235000019721 spearmint oil Nutrition 0.000 description 4
- 230000004584 weight gain Effects 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- 206010011224 Cough Diseases 0.000 description 3
- 208000005679 Eczema Diseases 0.000 description 3
- 230000036826 Excretion Effects 0.000 description 3
- 229940065521 Glucocorticoid inhalants for obstructive airway disease Drugs 0.000 description 3
- 208000006454 Hepatitis Diseases 0.000 description 3
- 210000003494 Hepatocytes Anatomy 0.000 description 3
- 210000004185 Liver Anatomy 0.000 description 3
- 206010041232 Sneezing Diseases 0.000 description 3
- 229940037128 Systemic Glucocorticoids Drugs 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000000996 additive Effects 0.000 description 3
- 238000004164 analytical calibration Methods 0.000 description 3
- 238000011088 calibration curve Methods 0.000 description 3
- 231100000406 dermatitis Toxicity 0.000 description 3
- 230000005713 exacerbation Effects 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000002757 inflammatory Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 159000000003 magnesium salts Chemical group 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000000414 obstructive Effects 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000003285 pharmacodynamic Effects 0.000 description 3
- 201000004681 psoriasis Diseases 0.000 description 3
- 230000002685 pulmonary Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 210000002821 Alveolar epithelial cell Anatomy 0.000 description 2
- 210000000621 Bronchi Anatomy 0.000 description 2
- 208000010247 Contact Dermatitis Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 206010020718 Hyperplasia Diseases 0.000 description 2
- 208000007903 Liver Failure Diseases 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 210000004379 Membranes Anatomy 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 210000003097 Mucus Anatomy 0.000 description 2
- 240000008962 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 210000001533 Respiratory Mucosa Anatomy 0.000 description 2
- 206010038683 Respiratory disease Diseases 0.000 description 2
- 208000006641 Skin Disease Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 210000001552 airway epithelial cell Anatomy 0.000 description 2
- 230000000172 allergic Effects 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000000954 anitussive Effects 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 231100000080 dermatitis contact Toxicity 0.000 description 2
- SPPIIOPGDLITJE-VLQRKCJKSA-N diazanium;(2S,3S,4S,5R,6S)-6-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-5-[(2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-3,4-dihy Chemical compound N.N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O SPPIIOPGDLITJE-VLQRKCJKSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 201000009910 diseases by infectious agent Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 238000002664 inhalation therapy Methods 0.000 description 2
- 201000009673 liver disease Diseases 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000003340 mental Effects 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000001575 pathological Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 210000004204 Blood Vessels Anatomy 0.000 description 1
- 206010008909 Chronic hepatitis Diseases 0.000 description 1
- 210000002808 Connective Tissue Anatomy 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 210000000981 Epithelium Anatomy 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N Galactosamine Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010018987 Haemorrhage Diseases 0.000 description 1
- 206010019641 Hepatic cirrhosis Diseases 0.000 description 1
- 206010019705 Hepatic pain Diseases 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 208000006897 Interstitial Lung Disease Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- VAYOSLLFUXYJDT-RDTXWAMCSA-N LSD Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 1
- 210000000867 Larynx Anatomy 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 210000004698 Lymphocytes Anatomy 0.000 description 1
- 229950002454 Lysergide Drugs 0.000 description 1
- 206010025482 Malaise Diseases 0.000 description 1
- 210000001616 Monocytes Anatomy 0.000 description 1
- 210000004400 Mucous Membrane Anatomy 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 210000004279 Orbit Anatomy 0.000 description 1
- 208000001297 Phlebitis Diseases 0.000 description 1
- 206010062080 Pigmentation disease Diseases 0.000 description 1
- 210000002381 Plasma Anatomy 0.000 description 1
- 229960000502 Poloxamer Drugs 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 210000002966 Serum Anatomy 0.000 description 1
- 210000003491 Skin Anatomy 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N Trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 206010068760 Ulcers Diseases 0.000 description 1
- 206010046736 Urticarias Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- -1 amino acid salts Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000844 anti-bacterial Effects 0.000 description 1
- 230000000111 anti-oxidant Effects 0.000 description 1
- 230000002155 anti-virotic Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 231100000319 bleeding Toxicity 0.000 description 1
- 230000000740 bleeding Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000003182 bronchodilatating Effects 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000012085 chronic inflammatory response Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 231100001003 eczema Toxicity 0.000 description 1
- 230000003203 everyday Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000001815 facial Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000037308 hair color Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 230000003082 hepatotoxic Effects 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940121354 immunomodulators Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002427 irreversible Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 201000004044 liver cirrhosis Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N monochloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 230000002956 necrotizing Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000002640 oxygen therapy Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000002085 persistent Effects 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive Effects 0.000 description 1
- 230000001737 promoting Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reduced Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000035489 relative bioavailability Effects 0.000 description 1
- 230000000241 respiratory Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000027849 smooth muscle hyperplasia Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 229960005486 vaccines Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000002747 voluntary Effects 0.000 description 1
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021126412A JP7309791B2 (ja) | 2016-04-15 | 2021-08-02 | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610237175.3 | 2016-04-15 | ||
CN201610237175 | 2016-04-15 | ||
PCT/CN2017/080583 WO2017177966A1 (zh) | 2016-04-15 | 2017-04-14 | 异甘草酸或其盐的吸入制剂及其在制备治疗呼吸***疾病药物中的应用 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021126412A Division JP7309791B2 (ja) | 2016-04-15 | 2021-08-02 | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
Publications (4)
Publication Number | Publication Date |
---|---|
JP2019511556A JP2019511556A (ja) | 2019-04-25 |
JP2019511556A5 JP2019511556A5 (de) | 2020-05-21 |
JPWO2017177966A5 true JPWO2017177966A5 (de) | 2022-06-23 |
JP7166929B2 JP7166929B2 (ja) | 2022-11-08 |
Family
ID=60042326
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018554375A Active JP7166929B2 (ja) | 2016-04-15 | 2017-04-14 | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
JP2021126412A Active JP7309791B2 (ja) | 2016-04-15 | 2021-08-02 | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021126412A Active JP7309791B2 (ja) | 2016-04-15 | 2021-08-02 | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
Country Status (12)
Country | Link |
---|---|
US (2) | US20190117568A1 (de) |
EP (1) | EP3443954A4 (de) |
JP (2) | JP7166929B2 (de) |
KR (1) | KR102410183B1 (de) |
CN (2) | CN109069442B (de) |
AU (1) | AU2017251548B2 (de) |
BR (1) | BR112018071208A2 (de) |
EA (1) | EA201892350A1 (de) |
MX (1) | MX2018012461A (de) |
PH (1) | PH12018502195A1 (de) |
SG (2) | SG10202010192YA (de) |
WO (1) | WO2017177966A1 (de) |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4891221A (en) * | 1988-11-23 | 1990-01-02 | Edward Shanborm | Whole blood antiviral process and composition |
WO2005004913A1 (ja) * | 2003-07-09 | 2005-01-20 | Anges Mg, Inc. | デコイを含む薬学的組成物およびその使用方法 |
WO2005004845A1 (en) | 2003-07-11 | 2005-01-20 | Glaxo Group Limited | Pharmaceutical formulations comprising magnesium stearate |
CN101023953B (zh) * | 2006-07-24 | 2010-05-12 | 南开大学 | 治疗支气管哮喘的组合物 |
CN101190232B (zh) * | 2006-11-30 | 2011-08-17 | 江苏正大天晴药业股份有限公司 | 一种注射用异甘草酸镁冻干粉针剂及其制备方法 |
JP2008222682A (ja) * | 2007-03-15 | 2008-09-25 | Kumamoto Univ | 線維化肺疾患治療薬、気道粘液分泌細胞過形成抑制剤および気道塞栓治療薬 |
CN101396368B (zh) * | 2007-09-29 | 2010-12-01 | 江苏正大天晴药业股份有限公司 | 异甘草酸或其盐在制备治疗过敏性鼻炎药物中的应用 |
CN101669962A (zh) * | 2009-09-18 | 2010-03-17 | 杭州市第六人民医院 | 复合甘草酸氨基酸注射液及其制备方法和应用 |
WO2012026928A1 (en) * | 2010-08-25 | 2012-03-01 | Diacarta Llc | Use of glycyrrhetinic acid, glycyrrhizic acid and related compounds for prevention and/or treatment of pulmonary fibrosis |
CN103156930A (zh) * | 2011-12-19 | 2013-06-19 | 张亚军 | 一种含芍药和甘草提取物的呼吸道给药制剂 |
IN2014MN02000A (de) * | 2012-03-13 | 2015-08-14 | Respivert Ltd | |
CN102920936A (zh) * | 2012-09-17 | 2013-02-13 | 陈泉生 | 一种治疗呼吸道疾病的吸盐物及其制作方法 |
CN104042573A (zh) * | 2014-06-03 | 2014-09-17 | 青岛市市立医院 | 一种异甘草酸镁冻干粉针剂及其制备方法 |
CN106237297A (zh) * | 2016-08-30 | 2016-12-21 | 吉林紫鑫药业股份有限公司 | 一种用于治疗慢性支气管炎的药物组合物 |
-
2017
- 2017-04-14 AU AU2017251548A patent/AU2017251548B2/en active Active
- 2017-04-14 SG SG10202010192YA patent/SG10202010192YA/en unknown
- 2017-04-14 KR KR1020187033045A patent/KR102410183B1/ko active IP Right Grant
- 2017-04-14 MX MX2018012461A patent/MX2018012461A/es unknown
- 2017-04-14 WO PCT/CN2017/080583 patent/WO2017177966A1/zh active Application Filing
- 2017-04-14 SG SG11201809042SA patent/SG11201809042SA/en unknown
- 2017-04-14 JP JP2018554375A patent/JP7166929B2/ja active Active
- 2017-04-14 CN CN201780018629.0A patent/CN109069442B/zh active Active
- 2017-04-14 US US16/093,087 patent/US20190117568A1/en not_active Abandoned
- 2017-04-14 BR BR112018071208-6A patent/BR112018071208A2/pt not_active Application Discontinuation
- 2017-04-14 EA EA201892350A patent/EA201892350A1/ru unknown
- 2017-04-14 CN CN202010842414.4A patent/CN111920785B/zh active Active
- 2017-04-14 EP EP17781942.2A patent/EP3443954A4/de active Pending
-
2018
- 2018-10-12 PH PH12018502195A patent/PH12018502195A1/en unknown
-
2020
- 2020-08-07 US US16/988,289 patent/US11534398B2/en active Active
-
2021
- 2021-08-02 JP JP2021126412A patent/JP7309791B2/ja active Active
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8962601B2 (en) | Pharmaceutical products and composition comprising specific anticholinergic agents, β-2 agonists and corticosteroids | |
JPH09501700A (ja) | 気道流路および肺疾患の処置のためのモメタゾンフロエートの使用 | |
US9861647B2 (en) | Calcium glycerophosphate for treating and preventing respiratory diseases or conditions | |
WO2001070198A1 (en) | Stabilized dry powder formulations | |
AU2015261103A1 (en) | Combinations of tiotropium bromide, formoterol and budesonide for the treatment of COPD | |
WO2021211858A1 (en) | Inhalable formulation of a solution containing tiotropium bromide and olodaterol | |
JP2021506897A (ja) | フドステインのエアロゾル吸入用溶液製剤及びその製造方法 | |
US20030053956A1 (en) | Alkylaryl polyether alcohol polymers for treatment and prophylaxis of snoring, sleep apnea, sudden infant death syndrome and for improvement of nasal breathing | |
US20040009963A1 (en) | Use of salmeterol and fluticasone propionate combination | |
AU1321401A (en) | New combination comprising a beta 2 (beta)2 adreno receptor agonist and a leukotriene receptor antagonist | |
JP7309791B2 (ja) | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 | |
WO2019091082A1 (zh) | 一种羧甲司坦雾化吸入用溶液制剂及其制备方法 | |
JP2021176903A5 (de) | ||
CN116635018A (zh) | 吸入用药物组合物 | |
JPWO2017177966A5 (de) | ||
TW201016215A (en) | Compositions and uses of antiviral active pharmaceutical agents | |
KR20050094810A (ko) | 로플루미래스트와 r,r-포르모테롤을 포함하는 상승작용성조합물 | |
EA040563B1 (ru) | Применение препарата для ингаляции на основе изоглицирризината магния для лечения заболеваний дыхательной системы | |
WO2021211854A1 (en) | Inhalable formulation of a solution containing tiotropium bromide | |
JP2010520872A (ja) | 慢性閉塞性肺疾患治療剤 | |
AU2002247032A1 (en) | Alkyl aryl polyether alcohol polymers for improvement of nasal breathing |