CN114848606B - 一种丹酚酸b及其粉雾剂胶囊和制备方法 - Google Patents
一种丹酚酸b及其粉雾剂胶囊和制备方法 Download PDFInfo
- Publication number
- CN114848606B CN114848606B CN202210631631.8A CN202210631631A CN114848606B CN 114848606 B CN114848606 B CN 114848606B CN 202210631631 A CN202210631631 A CN 202210631631A CN 114848606 B CN114848606 B CN 114848606B
- Authority
- CN
- China
- Prior art keywords
- salvianolic acid
- parts
- powder
- lactose
- inhalac
- 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.)
- Active
Links
- SNKFFCBZYFGCQN-UHFFFAOYSA-N 2-[3-[3-[1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyloxy]-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=2OC(C=3C=C(O)C(O)=CC=3)C(C(=O)OC(CC=3C=C(O)C(O)=CC=3)C(O)=O)C=2C=1C=CC(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-UHFFFAOYSA-N 0.000 title claims abstract description 108
- SNKFFCBZYFGCQN-VWUOOIFGSA-N Lithospermic acid B Natural products C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2[C@H](C(=O)O[C@H](CC=3C=C(O)C(O)=CC=3)C(O)=O)[C@H](OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-VWUOOIFGSA-N 0.000 title claims abstract description 108
- STCJJTBMWHMRCD-UHFFFAOYSA-N salvianolic acid B Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=O)C=Cc2cc(O)c(O)c3OC(C(C(=O)OC(Cc4ccc(O)c(O)c4)C(=O)O)c23)c5ccc(O)c(O)c5 STCJJTBMWHMRCD-UHFFFAOYSA-N 0.000 title claims abstract description 108
- 239000000843 powder Substances 0.000 title claims abstract description 38
- 239000002775 capsule Substances 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000003795 chemical substances by application Substances 0.000 title abstract description 7
- 238000001694 spray drying Methods 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000002386 leaching Methods 0.000 claims abstract description 15
- 239000013078 crystal Substances 0.000 claims abstract description 7
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 229940098458 powder spray Drugs 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000011347 resin Substances 0.000 claims description 18
- 229920005989 resin Polymers 0.000 claims description 18
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000008101 lactose Substances 0.000 claims description 15
- 239000012488 sample solution Substances 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 11
- 229920001993 poloxamer 188 Polymers 0.000 claims description 11
- 229940044519 poloxamer 188 Drugs 0.000 claims description 11
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 9
- 229940067606 lecithin Drugs 0.000 claims description 9
- 235000010445 lecithin Nutrition 0.000 claims description 9
- 239000000787 lecithin Substances 0.000 claims description 9
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 claims description 8
- YMGFTDKNIWPMGF-UCPJVGPRSA-N Salvianolic acid A Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C(=C(O)C(O)=CC=1)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-UCPJVGPRSA-N 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 8
- 229930183842 salvianolic acid Natural products 0.000 claims description 8
- 239000000523 sample Substances 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
- 235000010355 mannitol Nutrition 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 239000007921 spray Substances 0.000 claims description 6
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 abstract description 11
- 238000000605 extraction Methods 0.000 abstract description 10
- 239000000463 material Substances 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 6
- 240000007164 Salvia officinalis Species 0.000 abstract description 4
- 235000005412 red sage Nutrition 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000009826 distribution Methods 0.000 abstract description 2
- 238000011403 purification operation Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 22
- 229940079593 drug Drugs 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical group CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 238000000889 atomisation Methods 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000003595 mist Substances 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 244000132619 red sage Species 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PAFLSMZLRSPALU-MRVPVSSYSA-N (2R)-3-(3,4-dihydroxyphenyl)lactic acid Chemical compound OC(=O)[C@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-MRVPVSSYSA-N 0.000 description 1
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 description 1
- WTPPRJKFRFIQKT-UHFFFAOYSA-N 1,6-dimethyl-8,9-dihydronaphtho[1,2-g][1]benzofuran-10,11-dione;1-methyl-6-methylidene-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-10,11-dione Chemical compound O=C1C(=O)C2=C3CCCC(=C)C3=CC=C2C2=C1C(C)=CO2.O=C1C(=O)C2=C3CCC=C(C)C3=CC=C2C2=C1C(C)=CO2 WTPPRJKFRFIQKT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- FVNMAWQFIILJGS-UHFFFAOYSA-N O.OC.CC#N.OC=O Chemical compound O.OC.CC#N.OC=O FVNMAWQFIILJGS-UHFFFAOYSA-N 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000304195 Salvia miltiorrhiza Species 0.000 description 1
- PAFLSMZLRSPALU-UHFFFAOYSA-N Salvianic acid A Natural products OC(=O)C(O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 238000012387 aerosolization Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000000572 bronchospasmolytic effect Effects 0.000 description 1
- -1 bronchospasmolytics Substances 0.000 description 1
- 229940074360 caffeic acid Drugs 0.000 description 1
- 235000004883 caffeic acid Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 238000009688 liquid atomisation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229940052404 nasal powder Drugs 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
Classifications
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/86—Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Otolaryngology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
丹酚酸B | 乳糖InhaLac 230 | 甘露醇 | 泊洛沙姆188 | 卵磷脂 | |
实施例3 | 60 | 100 | / | 0.6 | 0.2 |
实施例4 | 60 | 100 | / | 1.2 | 1.2 |
实施例5 | 30 | 50 | / | 0.3 | / |
实施例6 | 30 | 50 | / | 0.6 | / |
实施例7 | 60 | / | 100 | 0.6 | 1.2 |
实施例8 | 60 | / | 100 | 1.2 | 0.2 |
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210631631.8A CN114848606B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910783155.XA CN110563677B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
CN202210631631.8A CN114848606B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910783155.XA Division CN110563677B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114848606A CN114848606A (zh) | 2022-08-05 |
CN114848606B true CN114848606B (zh) | 2023-10-31 |
Family
ID=68775844
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210631631.8A Active CN114848606B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
CN201910783155.XA Active CN110563677B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910783155.XA Active CN110563677B (zh) | 2019-08-23 | 2019-08-23 | 一种丹酚酸b及其粉雾剂胶囊和制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN114848606B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1534010A (zh) * | 2003-03-27 | 2004-10-06 | 成都地奥制药集团有限公司 | 丹参的水溶性提取物及其制备方法和用途 |
WO2009076869A1 (zh) * | 2007-12-07 | 2009-06-25 | Lichao Yuan | 高纯度丹酚酸、制备方法及应用 |
CN102100742A (zh) * | 2003-03-27 | 2011-06-22 | 成都地奥制药集团有限公司 | 丹参的水溶性提取物及其制备方法和用途 |
CN103923042A (zh) * | 2013-01-15 | 2014-07-16 | 天津天士力现代中药资源有限公司 | 丹酚酸b提取物的制备方法 |
CN104130226A (zh) * | 2014-04-01 | 2014-11-05 | 王平 | 一种高含量丹参丹酚酸b的制备方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2459406A1 (en) * | 2001-08-30 | 2003-03-13 | Taipei-Veterans General Hospital | Salvianolic acid b |
CN1436553A (zh) * | 2002-02-08 | 2003-08-20 | 余琛 | 一种丹参有效成分的提取方法 |
CN1257710C (zh) * | 2002-11-12 | 2006-05-31 | 张军 | 一种丹参药材中有效部位的制剂及其制备方法 |
US20050037094A1 (en) * | 2003-07-31 | 2005-02-17 | Xijun Yan | Composition for heart disease, its active ingredients, method to prepare same and uses thereof |
CN101530409A (zh) * | 2008-03-13 | 2009-09-16 | 天津天士力制药股份有限公司 | 丹酚酸b的抗血栓应用 |
CN101574337B (zh) * | 2008-05-05 | 2012-05-09 | 天津天士力制药股份有限公司 | 丹酚酸b和羟乙基淀粉的配伍对内毒素诱导的微循环障碍的预防和治疗 |
JP5755633B2 (ja) * | 2009-03-30 | 2015-07-29 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドTasly Pharmaceutical Group Co., Ltd. | 新規サルビアノール酸化合物l、その調製方法及び使用 |
CN103923043B (zh) * | 2013-01-15 | 2018-11-09 | 天津天士力现代中药资源有限公司 | 一种有效制备丹酚酸b提取物的方法 |
CN104910112B (zh) * | 2015-04-28 | 2018-03-27 | 南京宸翔医药研究有限责任公司 | 一种中药丹参有效成分丹酚酸b的制备方法、药物制剂及临床应用 |
-
2019
- 2019-08-23 CN CN202210631631.8A patent/CN114848606B/zh active Active
- 2019-08-23 CN CN201910783155.XA patent/CN110563677B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1534010A (zh) * | 2003-03-27 | 2004-10-06 | 成都地奥制药集团有限公司 | 丹参的水溶性提取物及其制备方法和用途 |
CN102100742A (zh) * | 2003-03-27 | 2011-06-22 | 成都地奥制药集团有限公司 | 丹参的水溶性提取物及其制备方法和用途 |
WO2009076869A1 (zh) * | 2007-12-07 | 2009-06-25 | Lichao Yuan | 高纯度丹酚酸、制备方法及应用 |
CN103923042A (zh) * | 2013-01-15 | 2014-07-16 | 天津天士力现代中药资源有限公司 | 丹酚酸b提取物的制备方法 |
CN104130226A (zh) * | 2014-04-01 | 2014-11-05 | 王平 | 一种高含量丹参丹酚酸b的制备方法 |
Non-Patent Citations (3)
Title |
---|
"丹参中丹参酮IIA和丹酚酸B的提取与纯化工艺研究";熊加伟 等;《天然产物研究与开发》;第29卷;第1396-1402,1379页 * |
"丹参总酚酸肺部吸入给药的评价研究";黎翊君;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》(第8期);E057-175:第9,24-25,42-51页 * |
中国医学科学院药物研究所编著.《中草药现代研究》.中国协和医科大学出版社,2010,(第1版),第630-633页. * |
Also Published As
Publication number | Publication date |
---|---|
CN114848606A (zh) | 2022-08-05 |
CN110563677A (zh) | 2019-12-13 |
CN110563677B (zh) | 2022-06-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2905267T3 (es) | Composición de medicina tradicional china, y preparación y aplicación de la misma | |
TW201521754A (zh) | 中藥組合物及其製劑和用途 | |
CN114848606B (zh) | 一种丹酚酸b及其粉雾剂胶囊和制备方法 | |
CN1310029C (zh) | 良附滴丸的质量控制方法 | |
CN102058642A (zh) | 人参次苷提取物及制备方法 | |
CN112516219A (zh) | 一种治疗***性红斑狼疮中药颗粒的制备工艺和质量控制方法 | |
CN1947736A (zh) | 一种灯盏细辛注射制剂的制备方法及其应用 | |
CN103142474B (zh) | 以高纯度银杏内酯b为活性成分的组合物及其制备方法 | |
CN113116935B (zh) | 蟾皮甾烯总内酯提取物及其制备方法和用途 | |
CN115006419A (zh) | 拟人参皂苷f11在制备治疗心力衰竭药物中的应用、治疗心力衰竭的药物及制备方法 | |
WO2016150355A1 (zh) | 提高绿原酸生物利用度的绿原酸酰化物及应用 | |
EP3777844B1 (en) | Method for preparing solution formulation for aerosol inhalation of naringenin | |
CN112500358A (zh) | 赛乐西帕晶型及其制备方法 | |
CN106974917B (zh) | 茯苓皮三萜在制备治疗肾病药物中的应用 | |
CN115420886B (zh) | 基于二氧化钛微球提取血浆中脂质体并测定游离药物、包裹药物和总药物含量的方法 | |
CN118141954B (zh) | 一种猴耳环可溶性粉剂及其制备方法 | |
CN114748432B (zh) | 一种中药复方颗粒的制备工艺 | |
CN109846841B (zh) | 一种速效氯巴占口服冻干制剂及其制备方法 | |
CN117940442A (zh) | 苦丁皂苷a化合物的晶型、其药物组合物和用途 | |
CN110624047B (zh) | 一种中药降脂组合物及其制备方法和用途 | |
CN107625774A (zh) | 薏苡茎叶中环阿乔醇在抗肿瘤药物的应用及其提取方法 | |
CN113559086A (zh) | 一种含氯喹类治疗剂的吸入剂及其制备方法 | |
CN112641795A (zh) | 一种治疗功能失调性子宫出血的头顶一颗珠有效部位及制备方法 | |
CN116270691A (zh) | 一种药物组合物 | |
CN1718192A (zh) | 一种洋参二醇皂苷粉针剂及其制备方法 |
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 |
Inventor after: Liu Yong Inventor after: Gao Chongkai Inventor after: Huang Huiqiu Inventor before: Gao Chongkai Inventor before: Huang Huiqiu |
|
CB03 | Change of inventor or designer information | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20230209 Address after: 516007 No.199 Nan'an Road, Huicheng District, Huizhou City, Guangdong Province Applicant after: JIUHUI PHARMACEUTICAL CO.,LTD. Applicant after: Huizhou Jiuhui Pharmaceutical Co.,Ltd. Address before: 516007 No.199 Nan'an Road, Huicheng District, Huizhou City, Guangdong Province Applicant before: JIUHUI PHARMACEUTICAL CO.,LTD. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant |