CN114099480A - 一种雾化吸入型虎杖苷溶液及制备方法 - Google Patents
一种雾化吸入型虎杖苷溶液及制备方法 Download PDFInfo
- Publication number
- CN114099480A CN114099480A CN202010860303.6A CN202010860303A CN114099480A CN 114099480 A CN114099480 A CN 114099480A CN 202010860303 A CN202010860303 A CN 202010860303A CN 114099480 A CN114099480 A CN 114099480A
- Authority
- CN
- China
- Prior art keywords
- polydatin
- solution
- tromethamine
- injection
- water
- 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
- HSTZMXCBWJGKHG-UHFFFAOYSA-N (E)-piceid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(C=CC=2C=CC(O)=CC=2)=C1 HSTZMXCBWJGKHG-UHFFFAOYSA-N 0.000 title claims abstract description 122
- 229960003764 polydatin Drugs 0.000 title claims abstract description 122
- HSTZMXCBWJGKHG-CUYWLFDKSA-N trans-piceid Polymers O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 HSTZMXCBWJGKHG-CUYWLFDKSA-N 0.000 title claims abstract description 122
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000000243 solution Substances 0.000 claims abstract description 90
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims abstract description 60
- 229960000281 trometamol Drugs 0.000 claims abstract description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 52
- 239000008215 water for injection Substances 0.000 claims abstract description 41
- 238000003756 stirring Methods 0.000 claims abstract description 40
- 238000001914 filtration Methods 0.000 claims abstract description 21
- 239000012528 membrane Substances 0.000 claims abstract description 20
- 239000000443 aerosol Substances 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 10
- 238000012859 sterile filling Methods 0.000 claims abstract description 10
- 238000011146 sterile filtration Methods 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 4
- 239000010419 fine particle Substances 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 3
- 230000029219 regulation of pH Effects 0.000 claims 1
- 230000007928 solubilization Effects 0.000 claims 1
- 238000005063 solubilization Methods 0.000 claims 1
- 208000000059 Dyspnea Diseases 0.000 abstract description 2
- 206010013975 Dyspnoeas Diseases 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 21
- 238000000889 atomisation Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000006184 cosolvent Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- 230000004089 microcirculation Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- -1 stilbene glycoside compounds Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 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 description 1
- WDJUZGPOPHTGOT-OAXVISGBSA-N Digitoxin Natural products O([C@H]1[C@@H](C)O[C@@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@@](C)([C@H](C6=CC(=O)OC6)CC5)CC4)CC3)CC2)C[C@H]1O)[C@H]1O[C@@H](C)[C@H](O[C@H]2O[C@@H](C)[C@@H](O)[C@@H](O)C2)[C@@H](O)C1 WDJUZGPOPHTGOT-OAXVISGBSA-N 0.000 description 1
- 244000166124 Eucalyptus globulus Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 241001289529 Fallopia multiflora Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 206010022773 Intracranial pressure increased Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000219926 Myrtaceae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 241000218657 Picea Species 0.000 description 1
- 241000218641 Pinaceae Species 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000219050 Polygonaceae Species 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- 208000010476 Respiratory Paralysis Diseases 0.000 description 1
- 240000001341 Reynoutria japonica Species 0.000 description 1
- 235000018167 Reynoutria japonica Nutrition 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 206010044541 Traumatic shock Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- WDJUZGPOPHTGOT-XUDUSOBPSA-N digitoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)CC5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O WDJUZGPOPHTGOT-XUDUSOBPSA-N 0.000 description 1
- 229960000648 digitoxin Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000001309 inhibitory effect on influenza Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000009941 intracranial hypertension Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 208000019180 nutritional disease Diseases 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Otolaryngology (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种雾化吸入型虎杖苷溶液及制备方法。溶液包括:活性成分虎杖苷、起助溶和pH调节作用的氨丁三醇和注射用水。制备方法包括:S1,将1/2处方量的氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入虎杖苷,搅拌至其充分分散于注射用水中;S2,分四次加入剩余1/2处方量的氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.0‑10.0,补加注射用水定容至处方总量,搅拌使其混合均匀;S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。本发明溶液适用于无自主吸入能力的婴幼儿童和主动呼吸困难患者,本发明的制备方法工艺简单,重现性好,易于大规模工业化生产。
Description
技术领域
本发明涉及中药制剂领域,具体涉及一种雾化吸入型虎杖苷溶液及制备方法。
背景技术
虎杖苷是蓼科植物虎杖的根茎中的活性成分,具有较强的生理活性。目前在蓼科植物何首乌根、松科库页云杉树皮、桃金娘科桉树属等72种植物中均有发现,分布广泛。虎杖苷属于二苯乙烯苷类化合物,易溶于乙醇、丙酮,微溶于水、乙酸乙酯、醋酸丁酯等,几乎不溶于乙醚、石油醚等。
近年来虎杖苷因其较强的生理活性,国内外对其药理作用研究较为广泛。现代药理研究表明,虎杖苷具有通过增加单个细胞中的游离钙离子浓度而直接增强心肌收缩性,产生比洋地黄苷更优越的强心功能,它不但使心肌收缩更有力,而且使心肌舒张更彻底,从而大大的提高心肌工作效率;虎杖苷在体内外都有抑制花生四烯酸(AA)、二磷酸腺苷(ADP)和肾上腺素(AD)诱导的兔血小板聚集作用;虎杖苷静脉注射能促进微循环中出现动脉血流,减轻烧伤后微血栓形成,善微循环;虎杖苷具有护肝脏,抑制类脂质过氧化物在肝脏堆积的作用;具有降血脂、抗脂质过氧化作用;虎杖苷具有体外抗肠道病毒71型的活性;另外对流感亚洲甲型京科68~1株病毒、孤儿病毒、单纯疱疹病毒均有抑制作用。
现有技术中公开的虎杖苷制剂有注射液制剂,国内有虎杖苷注射液作为治疗心肌缺血、脑缺血、休克等心脑血管疾病,进行临床申请及补充申请,受理号分别为CXZL0500018和CXZB0600214。同时作为中毒烧伤和创伤性休克临床应用进行临床试验,登记号分别为CTR20132636和CTR20160804。 2013年该注射液向美国FDA提交的美国II期临床试验申请正式获得FDA受理。
现有技术中公开的虎杖苷制剂除注射液制剂外,还有口服液及冻干粉针剂,但未进入临床使用。如中国专利CN100408043C公开了一种可作为注射剂、口服液、气雾剂或喷雾剂的溶液制剂。其由选自虎杖苷的主成分、选自注射用水的溶剂、选自乙醇的潜溶剂、选自丙二醇和乙醇混合液的助溶剂等成分组成。其乙醇用量为50%-80%,丙二醇用量为0%-50%。注射剂因需根据医嘱由技术熟练的人注射以保证安全,一般不能自己使用,且注射的给药方式会引起疼痛。且其中大量的乙醇用量,极易引起中枢神经系统的抑制作用,还可以伴有神经错乱、狂躁、活动不协调尿便失禁、血压下降、呼吸麻痹、颅内压增高等急性乙醇中毒现象。长期使用还可以造成营养障碍、慢性胃炎、胃溃疡、肝硬化、多发神经病等慢性疾病。WTO根据代谢和毒性试验数据,降日摄入量定为每公斤体重25mg,含有35%丙二醇的处方能至溶血。按照专利公开的处方,含有高浓度乙醇和丙二醇,无法直接用于注射给药,毒副作用风险很大,迄今尚无具有临床应用价值。且通过专利处方配制的溶液,通过试验验证因含有5%丙二醇,即无法实现有效雾化粒径,无法雾化吸入,且稳定性极差,所以其所述喷雾剂和喷雾剂处方亦无实际应用价值。
另外,中国专利CN101062044B公开了一种高浓度虎杖苷药物组合物,其由选自虎杖苷的主成分、选自注射用水的溶剂、选自葡甲胺和/或环糊精为助溶剂的药物组合物,其还可以包括缓冲液、甘露醇为冻干剂的支撑剂。按照专利处方配制溶液后发现,葡甲胺、磺丁基倍他环糊精、环糊精作为助溶剂时,其溶液稳定性差,室温放置两天均有不同程度的性状改变即颜色加深,冷藏两天有不同程度药物析出现象,且其所涉及气雾剂处方中助溶剂用量,其雾化粒径不能满足肺部沉积。所以到目前为止,尚无具有临床应用价值的虎杖苷制剂面世,有关数据显示,相关注射剂补充申请的审评结论不予通过。
由于现有虎杖苷的给药制剂,存在不同程度的各种缺陷,不适合吸入给药,因此为满足市场安全有效的用药需求,开发一种新的安全有效且质量稳定可控的虎杖苷新剂型,是虎杖苷制剂应用中亟待解决的问题。
发明内容
鉴于现有技术存在的问题,提出了本发明的一种雾化吸入型虎杖苷溶液及制备方法,以便克服上述问题或者至少部分地解决上述问题。
为了实现上述目的,本发明采用了如下技术方案:
根据本发明的一个方面,提供一种雾化吸入型虎杖苷溶液,所述溶液包括:活性成分虎杖苷、起助溶和pH调节作用的氨丁三醇和注射用水。
优选地,所述雾化吸入型虎杖苷溶液中虎杖苷的含量为0.4-5mg/ml,氨丁三醇的剂量为2-62mg/ml。
优选地,所述雾化吸入型虎杖苷溶液中虎杖苷的含量为1-5mg/ml,氨丁三醇的剂量为12-61.1mg/ml。
优选地,所述雾化吸入型虎杖苷溶液的pH值为9.0-10.0。
优选地,所述雾化吸入型虎杖苷溶液的单次给药剂量为2ml-5ml。
优选地,所述雾化吸入型虎杖苷溶液的日给药时间为5min-120min,优选为5min-60min,更优选为10min-30min。
优选地,所述雾化吸入型虎杖苷溶液给药时的空气动力学质量中直径为 1-5μm,优选地,空气动力学质量中直径为2-4μm,微细粒子百分比为30% -70%,优选地,微细粒子百分比为40%-70%。
优选地,所述雾化吸入型虎杖苷溶液可通过装填于单剂量的雾化吸入装置向肺部给药。
根据本发明的另一个方面,提供一种雾化吸入型虎杖苷溶液的制备方法,该方法包括如下步骤,
S1,将1/2处方量的氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余1/2处方量的氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.0-10.0,补加注射用水定容至处方总量,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
下面为雾化吸入型虎杖苷溶液的处方研究试验
1.助溶剂的选择
以吐温80、PEG400、丙二醇、甘油、辛酸癸酸聚乙二醇甘油酯为助溶剂,考察其对虎杖苷在水中溶解度影响,其中,用量为20ml,实验现象见表1。
表1:
由表1可知,吐温80、PEG400、丙二醇、辛酸癸酸聚乙二醇甘油酯对虎杖苷有不同程度助溶作用,但都存在析晶、溶液难以雾化使用等问题,因此上述试剂不易作为虎杖苷溶液处方中的助溶剂。
2.增溶剂的选择
以氢氧化钠、磷酸氢二钠、碳酸钠、碳酸氢钠、氨丁三醇为增溶剂,考察其对虎杖苷在水中溶解度的影响,实验现象见表2。
表2:
由表2中可知,氨丁三醇适合作为虎杖苷溶液处方中的增溶剂。
3.pH调节剂的选择
经试验研究,虎杖苷在碱性条件下更易溶于水,在强碱性条件下易分解,氨丁三醇为非钠的氨基缓冲碱,其水溶液为碱性水溶液,且氨丁三醇随着用量增加而碱性增强。为增加虎杖苷溶解性且避免虎杖苷溶液因强碱性或局部瞬间强碱性而造成分解,因此选用氨丁三醇作为虎杖苷溶液的pH调节剂。
因此,虎杖苷溶液的处方为:虎杖苷、氨丁三醇和注射用水。
4.pH值范围的考察
按照雾化吸入型虎杖苷溶液的处方,分别在pH值为8.5、8.8、9.0、9.3、 9.5、9.8、10.0制备虎杖苷溶液,考察不同pH值条件下制剂的稳定性,将制备的溶液冷藏在2-8℃,0天、10天后测定结果见表3。
表3:
由表3可知,雾化吸入用虎杖苷溶液的制剂pH值在9.0-10.0时,制剂的稳定性更优;pH值低于9.0,制剂不稳定,因此pH值范围选用9.0-10.0。
本发明的有益效果是:
1、本发明提供的雾化吸入型虎杖苷溶液不含另外的pH调节剂、缓冲液、防腐剂及抗氧剂,通过调整单一辅料即能达到良好的稳定性及雾化效果,工艺简单,重现性好,易于大规模工业化生产。
2、本发明制备的雾化吸入型虎杖苷溶液,为无自主吸入能力的婴幼儿童和主动呼吸困难患者提供了一种安全有效的药物剂型。
3、本发明的制备方法采用过滤除菌工艺,在保障产品无菌水平的同时,进一步提高了制剂的稳定性,质量安全可靠。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚,下面将对本发明实施方式作进一步地详细描述。
实施例1:配置雾化吸入型虎杖苷溶液200支,每支为2ml,规格为0.4mg/ml。
名称 | 用量 |
虎杖苷 | 0.16g |
氨丁三醇 | 0.8g |
加注射用水至 | 400ml |
步骤如下:
S1,将0.4g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入0.16g 虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余0.4g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.0,补加注射用水定容至400ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例2:配置雾化吸入型虎杖苷溶液200支,每支为2ml,规格为0.75mg/ml。
处方:
名称 | 用量 |
虎杖苷 | 0.3g |
氨丁三醇 | 3.2g |
加注射用水至 | 400ml |
步骤如下:
S1,将1.6g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入0.3g 虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余1.6g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.3,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例3:配置雾化吸入型虎杖苷溶液250支,每支为4ml,规格为1mg/ml。
名称 | 用量 |
虎杖苷 | 1g |
氨丁三醇 | 12.1g |
加注射用水至 | 1000ml |
步骤如下:
S1,将6.05g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入1g 虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余6.05g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.4,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例4:配置雾化吸入型虎杖苷溶液250支,每支为4ml,规格为2mg/ml。
名称 | 用量 |
虎杖苷 | 2g |
氨丁三醇 | 25.2g |
加注射用水至 | 1000ml |
步骤如下:
S1,将12.6g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入2g 虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余12.6g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.5,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例5:配置雾化吸入型虎杖苷溶液200支,每支为5ml,规格为3mg/ml。
名称 | 用量 |
虎杖苷 | 3g |
氨丁三醇 | 37.5g |
加注射用水至 | 1000ml |
步骤如下:
S1,将18.75g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入 3g虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余18.75g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.7,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例6:配置雾化吸入型虎杖苷溶液200支,每支为5ml,规格为4mg/ml。
步骤如下:
S1,将24.65g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入 4g虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余24.65g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9.8,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
实施例7:配置雾化吸入型虎杖苷溶液250支,每支为4ml,规格为5mg/ml。
名称 | 用量 |
虎杖苷 | 5g |
氨丁三醇 | 61.1g |
加注射用水至 | 1000ml |
步骤如下:
S1,将30.55g氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入 3g虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余30.55g氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至10.0,补加注射用水定容至1000ml,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
下面是对实施例1-7的试验结果进行考察。
1、稳定性考察
将实施例1-7中制备的雾化吸入型虎杖苷溶液放置在2-8℃冷藏10天后,试验结果见表4,
表4:
由表4可知,实施例1-7制备的雾化吸入型虎杖苷溶液的含量10天后均无变化,可见,制备的雾化吸入型虎杖苷溶液的稳定性较好。
2、空气动力学雾化粒径测定
采用新帕泰克粒径测定仪,对实施例1-7中制备的雾化粒径进行测定,测定结果见表5,
表5:
由表5可知,本发明实施例1-7中的雾化粒径X50均在2~4μm之间,X84< 6μm。
3、雾化吸入型虎杖苷溶液雾化性能测定
分别采用德国百瑞PARI BOY SX型雾化器、NEU22型欧姆龙雾化器(压缩空气雾化)、英华融泰(压缩空气式雾化器)雾化器,取实施例1溶液2ml、实施例2溶液2ml、实施例3溶液4ml、实施例4溶液4ml、实施例5溶液 5ml、实施例6溶液5ml、实施例7溶液4ml进行雾化,记录微细粒子百分比FPF(%)及空气动力学质量中直径MMAD(μm),结果见表6。
表6:
由表6结果可知,采用本发明制备的雾化吸入型虎杖苷溶液具有较好的雾化特性,其空气动力学质量中直径在1-5μm,微细粒子百分比为30%-70%,能够满足雾化吸入的要求。
4、吸入型虎杖苷溶液的雾化时间测定
分别采用德国百瑞PARI BOY SX型雾化器、NEU22型欧姆龙雾化器(压缩空气雾化)、英华融泰(压缩空气式雾化器)雾化器,取实施例1溶液2ml、实施例2溶液2ml、实施例3溶液4ml、实施例4溶液4ml、实施例5溶液 5m、实施例6溶液5ml、实施例7溶液4ml进行雾化,记录雾化结束时间(以无白色雾状喷出为准),结果见表7。
表7:
由表7可知,采用本发明制备的吸入型虎杖苷溶液的雾化吸入给药时间在10-30min之间。
以上对本发明进行了详细介绍。以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出对本领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也落入本发明权利要求的保护范围内。
Claims (9)
1.一种雾化吸入型虎杖苷溶液,其特征在于,所述溶液包括:活性成分虎杖苷、起增溶和pH调节作用的氨丁三醇、注射用水。
2.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液中虎杖苷的含量为0.4-5mg/ml,氨丁三醇的剂量为2-62mg/ml。
3.如权利要求2所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液中虎杖苷的含量为1-5mg/ml,氨丁三醇的剂量为12-61.1mg/ml。
4.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液的pH值为9.0-10.0。
5.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液的单次给药剂量为2ml-5ml。
6.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液的单次给药时间为5min-120min,优选为5min-60min,更优选为10min-30min。
7.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液给药时的空气动力学质量中直径为1-5μm,优选地,空气动力学质量中直径为2-4μm,微细粒子百分比为30%-70%,优选地,微细粒子百分比为40%-70%。
8.如权利要求1所述的溶液,其特征在于,所述雾化吸入型虎杖苷溶液可通过装填于单剂量的雾化吸入装置向肺部给药。
9.如权利要求1-8任一项所述溶液的制备方法,其特征在于,该方法包括如下步骤,
S1,将1/2处方量的氨丁三醇和注射用水混合,搅拌至其全部溶解后,加入虎杖苷,搅拌至其充分分散于注射用水中;
S2,分四次加入剩余1/2处方量的氨丁三醇,搅拌使氨丁三醇和虎杖苷充分溶解,并调节溶液的pH至9-10.0,补加注射用水定容至处方总量,搅拌使其混合均匀;
S3,用0.45μm滤膜进行初滤,0.22μm滤膜进行精滤,无菌过滤后,灌装。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010860303.6A CN114099480A (zh) | 2020-08-25 | 2020-08-25 | 一种雾化吸入型虎杖苷溶液及制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010860303.6A CN114099480A (zh) | 2020-08-25 | 2020-08-25 | 一种雾化吸入型虎杖苷溶液及制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114099480A true CN114099480A (zh) | 2022-03-01 |
Family
ID=80373765
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010860303.6A Pending CN114099480A (zh) | 2020-08-25 | 2020-08-25 | 一种雾化吸入型虎杖苷溶液及制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114099480A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114652704A (zh) * | 2022-04-29 | 2022-06-24 | 兆科药业(广州)有限公司 | 一种曲前列尼尔软雾吸入剂 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108670950A (zh) * | 2018-06-29 | 2018-10-19 | 深圳海王医药科技研究院有限公司 | 一种不含有机溶剂的虎杖苷药物组合物及其制备方法 |
-
2020
- 2020-08-25 CN CN202010860303.6A patent/CN114099480A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108670950A (zh) * | 2018-06-29 | 2018-10-19 | 深圳海王医药科技研究院有限公司 | 一种不含有机溶剂的虎杖苷药物组合物及其制备方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114652704A (zh) * | 2022-04-29 | 2022-06-24 | 兆科药业(广州)有限公司 | 一种曲前列尼尔软雾吸入剂 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6375037B2 (ja) | 生薬等含有医薬組成物(肆) | |
CN107789340B (zh) | 一种穿心莲雾化吸入用溶液制剂及其制备方法 | |
EP2594283B1 (de) | Aerosolpräparat auf aprotininbasis zur behandlung von virusinfektionen der atemwege | |
CN106974898B (zh) | 一种急支雾化吸入用溶液制剂及其制备方法 | |
WO2019119720A1 (zh) | 一种福多司坦雾化吸入用溶液制剂及其制备方法 | |
US20240285658A1 (en) | Pharmaceutical assembly comprising tobramycin inhalation solution and use thereof | |
CN114099480A (zh) | 一种雾化吸入型虎杖苷溶液及制备方法 | |
US20100104669A1 (en) | Method for preparing an aqueous solution containing triterpenic acid, aqueous solution containing triterpenic acid, and use thereof | |
CN113368208A (zh) | 一种抗病毒雾化吸入用溶液制剂及其制备方法 | |
CN114796168A (zh) | 一种羧甲司坦雾化吸入用溶液制剂及其制备方法 | |
CN114159414A (zh) | 一种雾化吸入用法匹拉韦溶液及其制备方法 | |
CN101023953B (zh) | 治疗支气管哮喘的组合物 | |
CN114344380A (zh) | 一种止喘灵雾化吸入用溶液制剂及其制备方法 | |
CN112999204A (zh) | 一种双黄连雾化吸入用溶液制剂及其制备方法 | |
CN112957350A (zh) | 一种鱼腥草雾化吸入用溶液制剂及其制备方法 | |
DE69917658T3 (de) | Micronisierte pharmazeutische zusammensetzungen | |
CN107334754B (zh) | 一种清开灵雾化吸入用溶液制剂及其制备方法 | |
CN117205186B (zh) | 一种雷芬那辛吸入喷雾剂及其制备方法 | |
DE60202299T2 (de) | Pharmazeutische zusammensetzung enthaltend salmeterol und budesonid zur behandlung von atemkrankheiten | |
CN113456619A (zh) | 一种双嘧达莫吸入制剂及其制备方法 | |
CN110522786A (zh) | 一种吸入用紫花杜鹃溶液制剂及其制备方法 | |
CN115337311B (zh) | 一种治疗呼吸系统疾病的组合物及其制备方法 | |
CN113209056A (zh) | 一种金莲花雾化吸入用溶液制剂及其制备方法 | |
CN108283629A (zh) | 吸入用罗氟司特混悬液及其制备方法 | |
CN107773593A (zh) | 一种小儿清热止咳雾化吸入用溶液制剂及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20221221 Address after: 300385 E12, No. 1 Sizhi Dao, Xuefu Industrial Zone, Xiqing District, Tianjin Applicant after: INCREASE (TIANJIN) INNOVATIVE MEDICINE RESEARCH Co.,Ltd. Address before: 570208 Dalu Town, Qionghai City, Haikou City, Hainan Province Applicant before: STAR PHARMACEUTICAL Ltd. |
|
TA01 | Transfer of patent application right | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |