CN114246903B - 心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 - Google Patents
心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 Download PDFInfo
- Publication number
- CN114246903B CN114246903B CN202011009537.6A CN202011009537A CN114246903B CN 114246903 B CN114246903 B CN 114246903B CN 202011009537 A CN202011009537 A CN 202011009537A CN 114246903 B CN114246903 B CN 114246903B
- Authority
- CN
- China
- Prior art keywords
- radix
- extract
- preparation
- xintong
- parts
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 50
- 206010006458 Bronchitis chronic Diseases 0.000 title claims abstract description 33
- 206010006451 bronchitis Diseases 0.000 title claims abstract description 33
- 208000007451 chronic bronchitis Diseases 0.000 title claims abstract description 33
- 239000000463 material Substances 0.000 claims abstract description 39
- 241000512259 Ascophyllum nodosum Species 0.000 claims abstract description 35
- 241001474374 Blennius Species 0.000 claims abstract description 35
- 241000893536 Epimedium Species 0.000 claims abstract description 35
- 241000237502 Ostreidae Species 0.000 claims abstract description 35
- 235000018905 epimedium Nutrition 0.000 claims abstract description 35
- 235000020636 oyster Nutrition 0.000 claims abstract description 35
- 244000183685 Citrus aurantium Species 0.000 claims abstract description 34
- 235000007716 Citrus aurantium Nutrition 0.000 claims abstract description 34
- 240000002948 Ophiopogon intermedius Species 0.000 claims abstract description 7
- 244000046146 Pueraria lobata Species 0.000 claims abstract description 6
- 235000010575 Pueraria lobata Nutrition 0.000 claims abstract description 6
- 240000001341 Reynoutria japonica Species 0.000 claims abstract description 6
- 235000018167 Reynoutria japonica Nutrition 0.000 claims abstract description 6
- 235000006533 astragalus Nutrition 0.000 claims abstract description 6
- 241001061264 Astragalus Species 0.000 claims abstract description 4
- 210000004233 talus Anatomy 0.000 claims abstract description 4
- 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 claims abstract 2
- 244000132619 red sage Species 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 149
- 239000000284 extract Substances 0.000 claims description 91
- 239000000706 filtrate Substances 0.000 claims description 57
- 238000001914 filtration Methods 0.000 claims description 54
- 238000002156 mixing Methods 0.000 claims description 44
- 241000756943 Codonopsis Species 0.000 claims description 38
- 239000009636 Huang Qi Substances 0.000 claims description 38
- 239000002775 capsule Substances 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
- 239000000843 powder Substances 0.000 claims description 33
- 241001289529 Fallopia multiflora Species 0.000 claims description 29
- 241000382455 Angelica sinensis Species 0.000 claims description 20
- 238000005303 weighing Methods 0.000 claims description 18
- 241000125175 Angelica Species 0.000 claims description 14
- 235000001287 Guettarda speciosa Nutrition 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- 239000008213 purified water Substances 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 239000004014 plasticizer Substances 0.000 claims description 12
- 239000010135 fructus aurantii immaturus Substances 0.000 claims description 11
- 239000003094 microcapsule Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- 238000001291 vacuum drying Methods 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 8
- 239000000839 emulsion Substances 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 8
- 229930006000 Sucrose Natural products 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 239000005720 sucrose Substances 0.000 claims description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003995 emulsifying agent Substances 0.000 claims description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical group CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 4
- 240000007164 Salvia officinalis Species 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 230000001804 emulsifying effect Effects 0.000 claims description 4
- 239000000469 ethanolic extract Substances 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 239000008347 soybean phospholipid Substances 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
- -1 sucrose fatty acid ester Chemical class 0.000 claims description 4
- 108010060630 Lactoglobulins Proteins 0.000 claims description 3
- 229920002774 Maltodextrin Polymers 0.000 claims description 3
- 239000005913 Maltodextrin Substances 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 3
- KCYQMQGPYWZZNJ-BQYQJAHWSA-N hydron;2-[(e)-oct-1-enyl]butanedioate Chemical compound CCCCCC\C=C\C(C(O)=O)CC(O)=O KCYQMQGPYWZZNJ-BQYQJAHWSA-N 0.000 claims description 3
- 229940035034 maltodextrin Drugs 0.000 claims description 3
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 235000005412 red sage Nutrition 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 239000000230 xanthan gum Substances 0.000 claims description 3
- 229920001285 xanthan gum Polymers 0.000 claims description 3
- 235000010493 xanthan gum Nutrition 0.000 claims description 3
- 229940082509 xanthan gum Drugs 0.000 claims description 3
- 239000002131 composite material Substances 0.000 claims description 2
- 102000000119 Beta-lactoglobulin Human genes 0.000 claims 1
- 235000010469 Glycine max Nutrition 0.000 claims 1
- 229940107666 astragalus root Drugs 0.000 claims 1
- 241000700159 Rattus Species 0.000 abstract description 48
- 238000012360 testing method Methods 0.000 abstract description 23
- 230000000694 effects Effects 0.000 abstract description 20
- 206010011224 Cough Diseases 0.000 abstract description 17
- 210000001519 tissue Anatomy 0.000 abstract description 13
- 206010062717 Increased upper airway secretion Diseases 0.000 abstract description 12
- 210000004072 lung Anatomy 0.000 abstract description 12
- 208000026435 phlegm Diseases 0.000 abstract description 12
- 108090000174 Interleukin-10 Proteins 0.000 abstract description 10
- 108090000978 Interleukin-4 Proteins 0.000 abstract description 10
- 238000011282 treatment Methods 0.000 abstract description 8
- 206010061218 Inflammation Diseases 0.000 abstract description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 7
- 230000004054 inflammatory process Effects 0.000 abstract description 7
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 abstract description 6
- 208000006673 asthma Diseases 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 239000013585 weight reducing agent Substances 0.000 abstract description 3
- 230000003213 activating effect Effects 0.000 abstract description 2
- 206010016256 fatigue Diseases 0.000 abstract description 2
- 229940126680 traditional chinese medicines Drugs 0.000 abstract description 2
- 241000213006 Angelica dahurica Species 0.000 abstract 1
- 241000931143 Gleditsia sinensis Species 0.000 abstract 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract 1
- 230000003467 diminishing effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 25
- 229940079593 drug Drugs 0.000 description 18
- 239000008187 granular material Substances 0.000 description 18
- 239000013641 positive control Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 11
- 241000195493 Cryptophyta Species 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000000465 moulding Methods 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 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 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 6
- 238000005498 polishing Methods 0.000 description 6
- 238000010171 animal model Methods 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 229940001482 sodium sulfite Drugs 0.000 description 5
- 235000010265 sodium sulphite Nutrition 0.000 description 5
- 210000003437 trachea Anatomy 0.000 description 5
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000000556 factor analysis Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 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 3
- 239000001116 FEMA 4028 Substances 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 208000037656 Respiratory Sounds Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 206010047924 Wheezing Diseases 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000001341 hydroxy propyl starch Substances 0.000 description 3
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 229940126673 western medicines Drugs 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 241000045403 Astragalus propinquus Species 0.000 description 2
- 241000007126 Codonopsis pilosula Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 102000008192 Lactoglobulins Human genes 0.000 description 2
- 206010024642 Listless Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 208000017971 listlessness Diseases 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010067715 Gastrointestinal sounds abnormal Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
- 235000017276 Salvia Nutrition 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 210000003489 abdominal muscle Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000008576 chronic process Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000008183 oral pharmaceutical preparation Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910021487 silica fume Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229940071440 soy protein isolate Drugs 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000000534 thyroid cartilage Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
- A61K36/296—Epimedium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/34—Campanulaceae (Bellflower family)
- A61K36/344—Codonopsis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/483—Gleditsia (locust)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8968—Ophiopogon (Lilyturf)
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Abstract
本发明公开了心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法,属于中药技术领域。所述的心通制剂由黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味原料药材制成,具有益气活血,消炎化痰之功。药效学试验表明,本发明心通制剂具有抗炎、平喘、止咳作用,能有效改善慢性支气管炎大鼠倦怠无力、进食减少和体重下降等身体状况,可显著降低慢性支气管炎大鼠肺组织匀浆TNF‑α水平,同时使IL‑10、IL‑4水平升高,对慢性支气管炎有确切显著的治疗效果。
Description
技术领域
本发明涉及心通制剂的应用及其制备方法,具体涉及心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法,属于中医药技术领域。
背景技术
慢性支气管炎(Chronic Bronchitis)是由感染或非感染因素引起的气管、支气管黏膜及周围组织的慢性非特异性炎症。临床上以咳嗽、咳痰或伴有喘息及反复发作的慢性过程为特征,其病理特点是支气管腺体增生、粘液分泌增多。慢性支气管炎为临床常见病,发病率高,病情进展缓慢,反复发作,病程长久,若不及时治疗,可并发阻塞性肺气肿、支气管扩张,甚至肺动脉高压、肺源性心脏病等,危害严重,严重影响患者的工作和生活。
目前,西医治疗慢性支气管炎主要以抗感染为主,常选用消炎、平喘、扩张气管药、激素药等药物治疗。但西药只能对该病的急性发作起到一定的控制作用,且因多数为抗生素类药物,长期服用会产生耐药性,副作用大,治标不治本,复发率高。中医认为,慢性支气管炎多属于中医学中的“咳嗽”、“痰证”、“饮证”、“喘证”等疾病范畴。慢性支气管炎的发病,在外为六淫邪气侵袭,在内为肺脾肾三脏功能失调及虚损导致的痰邪壅盛,随着病情的发展,痰凝阻滞,气机不畅,气滞血瘀,势在必然。因此中医药多通过健脾补肾,宣肺化痰,止咳平喘等方法治疗慢性支气管炎。同时,对于慢性支气管炎的治疗除祛风、清热、消滞、除痰等法外,活血化瘀之法也应贯穿始终。
CN1287835C公开了一种中药组合物,由黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实13味原料药材制成,具益气补肾、软坚散结、活血化瘀、化痰通络功效,适用于胸痹气虚、痰淤交阻,心痛、心悸、胸闷气短、心烦乏力、脉沉细、弦滑、结代等证,临床上主要用于冠心病、心绞痛和高血脂的治疗。该发明的药品名称为心通口服液(批准文号:国药准字Z10920014)和心通颗粒(批准文号:国药准字Z20020098),以上产品的商品名称为均为鲁南厚普制药有限公司的中成药产品。
发明内容
本发明的目的是提供一种心通制剂在制备治疗慢性支气管炎药物中的应用。本发明处方产品为心通口服液(国药准字Z10920014)或心通颗粒(国药准字Z20020098),临床上用于冠心病、心绞痛和高血脂的治疗,在临床实际应用过程中发现本发明所述的用途,后经相关的药效学试验验证,疗效确切,具有较大的商业价值。
心通制剂在制备治疗慢性支气管炎药物中的应用,所述心通制剂由下列中药组分制成:
优选为:
药效学试验表明,心通制剂是治疗慢性支气管炎有效组方,具有抗炎、平喘、止咳作用,能有效改善慢性支气管炎大鼠倦怠无力、进食减少和体重下降等身体状况,具有抗炎、平喘、止咳作用,可显著降低慢性支气管炎大鼠肺组织匀浆TNF-α水平,同时使IL-10、IL-4水平升高,对慢性支气管炎有确切显著的治疗效果。
本发明的另一个目的是提供一种含有上述中药组合物的中药口服制剂及其制备方法,所述中药口服制剂为颗粒剂、口服液、胶囊剂和微囊中的一种。
所述的中药口服制剂的制备方法包括以下步骤:
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加6-9倍量60-80%的乙醇回流,每次1.5-2.5小时,滤过,合并滤液,得醇提液Ⅰ备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味原料药材加6-9倍量水煎煮,每次1.5-2.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.16-1.22的浸膏Ⅰ;
D、步骤B醇提液Ⅰ与步骤C浸膏Ⅰ合并,加乙醇使含醇量达60-70%,冷藏24-48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.12-1.18的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,经常规工序直接或加入药学上可接受的赋形剂制成口服药物制剂。
本发明优选的剂型是颗粒剂,所述心通颗粒的制备方法包括下列步骤:
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,合并滤液,得醇提液Ⅰ备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味原料药材加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.18的浸膏Ⅰ;
D、步骤B醇提液Ⅰ与步骤C浸膏Ⅰ合并,加乙醇使含醇量达65%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.15的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,带式真空干燥,粉碎,得心通提取物细粉,加入配方量的蔗糖粉:羟丙基淀粉:甘露醇=5:3:1混合物赋形剂,混匀,制成颗粒,干燥,整粒,即得。
本发明另一种优选的剂型是微囊制剂,所述心通微囊的制备方法包括下列步骤:
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味原料药材加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.16的浸膏Ⅰ;
D、步骤B醇提液Ⅰ与步骤C浸膏Ⅰ合并,加乙醇使含醇量达70%,冷藏36小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.18的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,制成颗粒,带式真空干燥,粉碎,得心通提取物细粉,备用;
F、按配方量称取步骤E心通提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,57℃条件下加热搅拌使溶解,配置成质量分数为31.5%的囊材溶液,冷却至室温,搅拌状态下加入心通提取物细粉和乳化剂,均质乳化,得乳化液,备用;
G、步骤F乳化液在进风温度158℃、喷雾压力0.395MPa、进料速度20.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。
优选地,步骤E中带式真空干燥的条件为真空度-0.08MPa--0.10Mpa,干燥温度59℃。
优选地,步骤F所述囊材为辛烯基琥珀酸酯化淀粉:β-乳球蛋白=5:3或大豆分离蛋白:麦芽糊精:黄原胶=7:3:0.5,抗粘剂为十八醇:二氧化钛=3:1或单硬脂酸甘油酯,增塑剂为聚乙二醇:柠檬酸=3:1或丙二醇。
优选地,步骤F所述乳化剂按重量计为蔗糖脂肪酸酯:大豆磷脂=7∶2的复合乳化剂,用量按质量分数计为制剂配方总量的1.22%。
为验证本发明心通制剂治疗慢性支气管炎的作用,发明人开展了相应动物试验研究。需要说明的是,动物试验研究所选取是本发明具有代表性的配方及其制备方法所得的样品,本发明所包含的其它配方及制备方法所得产品涉及的试验及其结果,由于篇幅限制,在此不一一穷举。
实验例1药物对慢性支气管炎模型大鼠全身状态的影响
1材料
1.1实验动物及饲料SPF级SD大鼠,雌雄各半,60只,体重(200±20)g,由鲁南制药集团股份有限公司提供,实验动物许可证号:SYXK(鲁)2018 0008。实验前在清洁级动物实验室适应性饲养1周,雌雄分开,室温20-25℃,相对湿度40%-60%,自然光照,自由摄食、饮水。
1.2仪器、试剂及药品AG285型电子分析天平(瑞士Mettler-Toledo公司);亚硫酸钠、硫酸(济南弘博化工有限公司);受试药物为实施例3心通颗粒,阳性对照药为桂龙咳喘宁胶囊(批号Z20053135,桂龙药业(安徽)有限公司)。
2方法
2.1分组与造模取SPF级SD大鼠60只,随机分为6组,即正常对照组、模型对照组、桂龙咳喘宁胶囊阳性对照组(简称“阳性对照组”)、心通颗粒高剂量组(简称“试验高剂量组”)、心通颗粒中剂量组(简称“试验中剂量组”)和心通颗粒低剂量组(简称“试验低剂量组”),每组10只,雌雄各半。除正常对照组外,将其余5组大鼠分批置于40cm×35cm×60cm的熏箱(熏箱上留有缝隙)内,利用3g的亚硫酸钠与过量的硫酸反应生成SO2,每日1次,每次30min,连续熏28d造模。
2.2给药28天造模后,各组均进行灌胃给药,根据《中药新药临床研究指导原则》中附录的不同动物的剂量折算系数进行剂量折算,其中阳性对照组灌服桂龙咳喘宁胶囊0.75g/kg受试药物心通颗粒成人用临床剂量为0.35g/(kg.d),试验高、中、低剂量组依次为4.24g/kg、2.12g/kg和1.06g/kg,相当于2倍、1倍和0.5倍人用等效剂量,正常对照组、模型对照组则给予等容量生理盐水灌服,每日1次,连续给药7天。
2.3检测指标及方法
观察大鼠全身状态:实验过程中,记录各组大鼠活动状态、毛发光泽度、进食饮水及体质量变化,观察各组大鼠呼吸情况。
2.4统计学处理采用SPSS19.0统计学软件进行分析,实验数据以“均数±标准差”的形式表示。多组间比较采用单因素方差分析,以P<0.05表示差异具有统计学意义。
3结果
造模7天后,与正常对照组大鼠相比,模型对照组大鼠出现了倦怠、活动减少、食欲减少等状况;造模14天之后,与正常对照组大鼠相比,模型对照组大鼠的体质量增长速度明显变缓;给药结束时,与正常对照组大鼠相比,模型对照组大鼠体质量增加量明显减少,差异具统计学意义(P<0.05),而且模型对照组大鼠体质量普遍偏轻,差异具统计学意义(P<0.05);与模型对照组大鼠相比,阳性对照组、试验高剂量组、试验中剂量组大鼠的体质量增加量明显升高,差异均具统计学意义(P<0.05),试验低剂量组大鼠的体质量增加量无显著性差异。结果见表1。
造模21天后,模型对照组大鼠皮毛枯槁,可听到气道痰鸣音,并且出现咳嗽、哮鸣、呼吸困难等现象。给药结束后,经给药治疗的阳性对照组、试验高剂量组、试验中剂量组大鼠气道痰鸣音减轻,咳嗽等现象得到缓解,模型对照组及试验低剂量组大鼠改善不明显。
表1心通颗粒对慢性支气管炎大鼠体质量的影响(n=10)
注:与正常对照组比较:P<0.05用“△”表示;与模型对照组比较:P<0.05用“**”表示。
实验例2药物对慢性支气管炎模型大鼠的镇咳作用
1材料
1.1实验动物及饲料同实验例1。
1.2仪器、试剂及药品AG285型电子分析天平(瑞士Mettler-Toledo公司);无水亚硫酸钠、亚硫酸钠、硫酸(济南弘博化工有限公司);受试药物为实施例3心通颗粒,阳性对照药为桂龙咳喘宁胶囊(批号Z20053135,桂龙药业(安徽)有限公司)。
2方法
2.1分组与造模取SPF级SD大鼠50只,随机分为5组,即模型对照组、桂龙咳喘宁胶囊阳性对照组(简称“阳性对照组”)、心通颗粒高剂量组(简称“试验高剂量组”)、心通颗粒中剂量组(简称“试验中剂量组”)和心通颗粒低剂量组(简称“试验低剂量组”),每组10只,雌雄各半。将5组大鼠分批置于40cm×35cm×60cm的熏箱(熏箱上留有缝隙)内,利用3g的亚硫酸钠与过量的硫酸反应生成SO2,每日1次,每次30min,连续熏28d造模。
2.2给药28天造模后,各组均进行灌胃给药,根据《中药新药临床研究指导原则》中附录的不同动物的剂量折算系数进行剂量折算,其中阳性对照组灌服桂龙咳喘宁胶囊0.75g/kg受试药物心通颗粒成人用临床剂量为0.35g/(kg.d),试验高、中、低剂量组依次为4.24g/kg、2.12g/kg和1.06g/kg,相当于2倍、1倍和0.5倍人用等效剂量,模型对照组则给予等容量生理盐水灌服,每日1次,连续给药7天。
2.3检测指标及方法
各组大鼠末次给药后1小时将盛有0.5g无水亚硫酸钠的蒸发皿置于500mL的干燥器内,迅速滴入50%的硫酸5mL,立即将大鼠放入含有二氧化硫气体的干燥器内,观察记录大鼠的咳嗽潜伏期(s)和2min内的咳嗽次数(注:大鼠咳嗽的判断以剧烈收缩腹肌并张嘴为准,有时可听到轻微咳嗽声)。
2.4统计学处理采用SPSS19.0统计学软件进行分析,实验数据以“均数±标准差”的形式表示。多组间比较采用单因素方差分析,以P<0.05表示差异具有统计学意义。
3结果
与模型对照组相比,阳性对照组及试验高、中、低剂量组的大鼠在2min内的咳嗽次数明显减少,咳嗽潜伏期明显延长,差异均具统计学意义(P<0.05),表明心通颗粒对慢性支气管炎大鼠具有明显的镇咳作用。结果见表2。
表2心通颗粒对慢性支气管炎大鼠二氧化硫引咳的作用(n=10)
注:与模型对照组比较:P<0.05用“**”表示。
实验例3药物对慢性支气管炎模型大鼠的祛痰作用
1材料
1.1实验动物及饲料同实验例1。
1.2仪器、试剂及药品AG285型电子分析天平(瑞士Mettler-Toledo公司)、酶标仪(南京华东电子集团医疗装备有限责任公司)、OLYMPUS BX51显微镜(OlympusCorporation,日本);酚红(美国Sigma公司)、亚硫酸钠、硫酸(济南弘博化工有限公司);受试药物为实施例3心通颗粒,阳性对照药为桂龙咳喘宁胶囊(批号Z20053135,桂龙药业(安徽)有限公司)。
2方法
2.1分组与造模同实验例2。
2.2给药28天造模后,各组均进行灌胃给药,根据《中药新药临床研究指导原则》中附录的不同动物的剂量折算系数进行剂量折算,其中阳性对照组灌服桂龙咳喘宁胶囊0.75g/kg受试药物心通颗粒成人用临床剂量为0.35g/(kg.d),试验高、中、低剂量组依次为4.24g/kg、2.12g/kg和1.06g/kg,相当于2倍、1倍和0.5倍人用等效剂量,模型对照组则给予等容量生理盐水灌服,每日1次,连续给药7天。
2.3检测指标及方法
各组大鼠实验前一天饥饿过夜,空腹16h,只供饮水。实验当天给药30min后,大鼠腹腔注射酚红10mL/kg,30min后颈椎脱臼处死,背位固定,分离气管,取自甲状软骨至气管开叉上方(长约1.5cm)一段气管,放入预先加入1mL生理盐水的试管中室温振荡30min。将溶液吸入试管加0.1mL浓度为1mol/L的NaOH,使用酶标仪在波长546nm处比色,所得吸光度代入酚红标准曲线方程,求出大鼠气管酚红排泄量为祛痰指标进行比较。
2.4统计学处理采用SPSS19.0统计学软件进行分析,实验数据以“均数±标准差”的形式表示。多组间比较采用单因素方差分析,以P<0.05表示差异具有统计学意义。
3结果
与模型对照组相比,阳性对照组及试验高、中、低剂量组均能显著增加大鼠气管的酚红排泄量,差异均具统计学意义(P<0.05),表明心通颗粒对慢性支气管炎大鼠具有明显的祛痰作用。结果见表3。
表3心通颗粒对慢性支气管炎大鼠酚红排泄量的影响(n=10)
注:与模型对照组比较:P<0.05用“**”表示。
实验例4药物对慢性支气管炎模型大鼠肺组织匀浆中TNF-a、IL-4、IL-10水平的影响
1材料
1.1实验动物及饲料同实验例1。
1.2仪器、试剂及药品AG285型电子分析天平(瑞士Mettler-Toledo公司)、FS-1可调高速匀浆机(广州市深华生物技术有限公司)、GL-20A全自动冷冻高速离心机(湖南仪器仪表总厂离心机厂);TNF-α、IL-4、IL-10试剂盒(Cusabio Biotech公司)、ELISA试剂盒(美国Sigma公司);亚硫酸钠、硫酸(济南弘博化工有限公司);受试药物为实施例3心通颗粒,阳性对照药为桂龙咳喘宁胶囊(批号Z20053135,桂龙药业(安徽)有限公司)。
2方法
2.1分组与造模同实验例1。
2.2给药28天造模后,各组均进行灌胃给药,根据《中药新药临床研究指导原则》中附录的不同动物的剂量折算系数进行剂量折算,其中阳性对照组灌服桂龙咳喘宁胶囊0.75g/kg受试药物心通颗粒成人用临床剂量为0.35g/(kg.d),试验高、中、低剂量组依次为4.24g/kg、2.12g/kg和1.06g/kg,相当于2倍、1倍和0.5倍人用等效剂量,正常对照组、模型对照组则给予等容量生理盐水灌服,每日1次,连续给药7天。
2.3检测指标及方法
制备肺组织匀浆及检测TNF-α、IL-4、IL-10水平:各组大鼠眼眶取血后,立即断颈处死,剖取气管和肺脏,取左肺下叶组织0.3g左右,在冰冷的生理盐水中漂洗,除去血液,滤纸拭干,称质量,置于小烧杯中。用移液管量取0.86%的预冷生理盐水2.7mL(按照实际组织质量的9倍计算),先将1.8mL置于小烧杯中,用眼科剪尽快剪碎组织块。将剪碎的组织倒入玻璃匀浆管中,用剩余的冷生理盐水冲洗小烧杯,一起倒入匀浆管中。将匀浆器下端插入盛有冰水混合物的器皿中,充分研磨使组织匀浆化。将制备好的匀浆以4000r/min离心10min,移取上清液,在-20℃下冻存待测。取上清液按试剂盒要求,用ELISA法测定TNF-α、IL-4、IL-10水平。
2.4统计学处理采用SPSS19.0统计学软件进行分析,实验数据以“均数±标准差(x±s)”的形式表示。多组间比较采用单因素方差分析,以P<0.05表示差异具有统计学意义。
3结果
与正常对照组相比,模型对照组大鼠肺组织匀浆中TNF-α水平明显升高,而IL-10、IL-4水平则明显降低,差异均具统计学意义(P<0.05)。与模型对照组相比,阳性对照组及试验高、中、低剂量可显著降低慢性支气管炎大鼠肺组织匀浆中升高的TNF-α,同时使下降的IL-10、IL-4水平升高,差异均具统计学意义(P<0.05)。结果见表4。
表4心通颗粒对慢性支气管炎大鼠肺组织匀浆中TNF-α、IL-10、IL-4水平的影响(n=10)
注:与正常对照组比较:P<0.05用“△”表示;与模型对照组比较:P<0.05用“**”表示。
以上实验结果表明,本发明心通制剂具有抗炎、平喘、止咳作用,能有效改善慢性支气管炎大鼠倦怠无力、进食减少和体重下降等身体状况,具有抗炎、平喘、止咳作用,可显著降低慢性支气管炎大鼠肺组织匀浆TNF-α水平,同时使IL-10、IL-4水平升高,对慢性支气管炎有确切显著的治疗效果。
具体实施方式
为了使本领域技术人员充分了解本发明,以下通过具体的实施例进一步说明本发明,但本领域技术人员应该知晓,本发明实施例并不以任何方式限制本发明。
实施例1心通胶囊的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加7倍量80%的乙醇回流2次,每次1.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加7倍量水煎煮2次,每次煎煮2.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.19的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达70%,冷藏36小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.17的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,真空度-0.09MPa--0.10Mpa,干燥温度63℃的条件下带式真空干燥,粉碎,得心通提取物细粉,加入配方量的淀粉、微粉硅胶、低取代羟丙基纤维素(重量比5:2:1),混匀,制粒,干燥,整粒,灌装,磨光机中抛光,剔除破损胶囊,即得。
实施例2心通口服液的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量60%的乙醇回流2次,每次2.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加9倍量水煎煮2次,每次煎煮1.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.22的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达60%,冷藏24小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.13的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,加入4倍量纯化水搅拌均匀得水提液,水提液滤过,每100ml滤液加入1g活性炭,加热至80℃保温60分钟,过滤除炭,加纯化水至配制总量,调节pH至7.5,每100ml药液加入0.5gβ-环糊精,控制包合温度40℃,包合60分钟,过滤,加纯化水至配制总量,过滤至澄明度合格后灌装,灭菌,包装即可。
实施例3心通颗粒的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.18的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达65%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.15的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,加入配方量的蔗糖粉:羟丙基淀粉:甘露醇=5:3:1混合物赋形剂,混匀,制成颗粒,干燥,整粒,即得。
实施例4心通胶囊的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加9倍量70%的乙醇回流2次,每次1.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加6倍量水煎煮2次,每次煎煮2.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.17的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达70%,冷藏36小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.12的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,真空度-0.09MPa--0.10Mpa,干燥温度62℃的条件下带式真空干燥,粉碎,得心通提取物细粉,加入配方量的淀粉、微晶纤维素(重量比7:2,混匀,制粒,干燥,整粒,灌装,磨光机中抛光,剔除破损胶囊,即得。
实施例5心通口服液的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加6倍量80%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.19的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达65%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.15的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,加入6倍量纯化水搅拌均匀得水提液,水提液滤过,每100ml滤液加入1g活性炭,加热至80℃保温60分钟,过滤除炭,加纯化水至配制总量,调节pH至7.0,每100ml药液加入0.6gβ-环糊精,控制包合温度40℃,包合60分钟,过滤,加纯化水至配制总量,过滤至澄明度合格后灌装,灭菌,包装即可。
实施例6心通微囊的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加7倍量60%的乙醇回流2次,每次2.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加7倍量水煎煮2次,每次煎煮1.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.16的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达70%,冷藏24小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.13的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,制成颗粒,在真空度-0.08MPa--0.10Mpa,干燥温度59℃条件下带式真空干燥,粉碎,得心通提取物细粉,备用;
F、按配方量称取步骤E心通提取物细粉、囊材、抗粘剂和增塑剂,其中囊材为辛烯基琥珀酸酯化淀粉:β-乳球蛋白=5:3,抗粘剂为十八醇:二氧化钛=3:1,增塑剂为丙二醇,将囊材、抗粘剂和增塑剂加入纯化水,57℃条件下加热搅拌使溶解,配置成质量分数为31.5%的囊材溶液,冷却至室温,搅拌状态下加入心通提取物细粉和按重量比计1.22%的蔗糖脂肪酸酯:大豆磷脂=7∶2的复合乳化剂,均质乳化,得乳化液,备用;
G、步骤F乳化液在进风温度158℃、喷雾压力0.395MPa、进料速度20.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。
实施例7心通颗粒的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.18的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达65%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.15的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,加入配方量的蔗糖粉:羟丙基淀粉:甘露醇=5:3:1混合物赋形剂,混匀,制成颗粒,干燥,整粒,即得。
实施例8心通口服液的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.19的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达65%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.16的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,加入5倍量纯化水搅拌均匀得水提液,水提液滤过,每100ml滤液加入1g活性炭,加热至80℃保温60分钟,过滤除炭,加纯化水至配制总量,调节pH至7.3,每100ml药液加入0.55gβ-环糊精,控制包合温度40℃,包合60分钟,过滤,加纯化水至配制总量,过滤至澄明度合格后灌装,灭菌,包装即可。
实施例9心通微囊的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加9倍量80%的乙醇回流2次,每次1.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加6倍量水煎煮2次,每次煎煮2.5小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.22的浸膏Ⅰ;
D、步骤C浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达70%,冷藏24小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.14的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,制成颗粒,在真空度-0.09MPa--0.10Mpa,干燥温度61℃条件下带式真空干燥,粉碎,得心通提取物细粉,备用;
F、按配方量称取步骤E心通提取物细粉、囊材、抗粘剂和增塑剂,其中囊材为大豆分离蛋白:麦芽糊精:黄原胶=7:3:0.5,抗粘剂为单硬脂酸甘油酯,增塑剂为聚乙二醇:柠檬酸=3:1,将囊材、抗粘剂和增塑剂加入纯化水,58℃条件下加热搅拌使溶解,配置成质量分数为30%的囊材溶液,冷却至室温,搅拌状态下加入心通提取物细粉和按重量比计1.22%的蔗糖脂肪酸酯:大豆磷脂=7∶2的复合乳化剂,均质乳化,得乳化液,备用;
G、步骤F乳化液在进风温度157℃、喷雾压力0.399MPa、进料速度21ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。
实施例10心通胶囊的制备
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加6倍量60%的乙醇回流2次,每次2.5小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味加7倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.17的浸膏Ⅰ;
D、步骤E浸膏Ⅰ与步骤A醇提液Ⅰ合并,加乙醇使含醇量达60%,冷藏48小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.16的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,真空度-0.09MPa--0.10Mpa,干燥温度62℃的条件下带式真空干燥,粉碎,得心通提取物细粉,加入配方量淀粉、微晶纤维素(重量比4:1),混匀,制粒,干燥,整粒,灌装,磨光机中抛光,剔除破损胶囊,即得。
Claims (2)
1.心通制剂在制备治疗慢性支气管炎药物中的应用;所述心通制剂为微囊剂,由下列中药组分制成:
黄芪26重量份 党参14重量份 麦冬10重量份 何首乌8重量份
淫羊藿8重量份 葛根22重量份 当归8重量份 丹参15重量份
皂角刺8重量份 海藻14重量份 昆布14重量份 牡蛎14重量份
枳实4重量份
所述微囊制剂的制备方法包括下列步骤:
A、称取黄芪、党参、麦冬、何首乌、淫羊藿、葛根、当归、丹参、皂角刺、海藻、昆布、牡蛎和枳实十三味药材,其中麦冬、淫羊藿、枳实净选,党参、海藻、昆布净选后切段,何首乌、葛根、牡蛎净选后切块,黄芪、当归、丹参净选后切片,皂角刺净选后粉碎成细粉,备用;
B、取葛根、丹参,加8倍量70%的乙醇回流2次,每次2小时,滤过,滤液合并,得醇提液Ⅰ,备用,药渣备用;
C、步骤B葛根、丹参药渣与其余黄芪、党参、麦冬、何首乌、淫羊藿、当归、皂角刺、海藻、昆布、牡蛎和枳实十一味原料药材加8倍量水煎煮2次,每次煎煮2小时,合并煎煮液,滤过,滤液减压浓缩至50-60℃时相对密度为1.16的浸膏Ⅰ;
D、步骤B醇提液Ⅰ与步骤C浸膏Ⅰ合并,加乙醇使含醇量达70%,冷藏36小时,滤过,滤液回收乙醇并减压浓缩至50-60℃时相对密度为1.18的浸膏Ⅱ,备用;
E、取步骤D浸膏Ⅱ,制成颗粒,带式真空干燥,粉碎,得心通提取物细粉,备用;
F、按配方量称取步骤E心通提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,57℃条件下加热搅拌使溶解,配置成质量分数为31.5%的囊材溶液,冷却至室温,搅拌状态下加入心通提取物细粉和乳化剂,均质乳化,得乳化液,备用;
G、步骤F乳化液在进风温度158℃、喷雾压力0.395MPa、进料速度20.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得;
其中,步骤F所述囊材为辛烯基琥珀酸酯化淀粉:β-乳球蛋白=5∶3或大豆分离蛋白:麦芽糊精:黄原胶=7∶3∶0.5,抗粘剂为十八醇:二氧化钛=3∶1或单硬脂酸甘油酯,增塑剂为聚乙二醇:柠檬酸=3∶1或丙二醇;
步骤F所述乳化剂按重量计为蔗糖脂肪酸酯:大豆磷脂=7∶2的复合乳化剂,用量按质量分数计为制剂配方总量的1.22%。
2.根据权利要求1所述的应用,其特征在于,步骤E中带式真空干燥的条件为真空度-0.08MPa--0.10Mpa,干燥温度59℃。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011009537.6A CN114246903B (zh) | 2020-09-23 | 2020-09-23 | 心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011009537.6A CN114246903B (zh) | 2020-09-23 | 2020-09-23 | 心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114246903A CN114246903A (zh) | 2022-03-29 |
CN114246903B true CN114246903B (zh) | 2023-12-05 |
Family
ID=80788620
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011009537.6A Active CN114246903B (zh) | 2020-09-23 | 2020-09-23 | 心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114246903B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1628837A (zh) * | 2004-08-30 | 2005-06-22 | 鲁南制药股份有限公司 | 一种治疗冠心病、心绞痛的药物组合物及其制备方法 |
CN103083597A (zh) * | 2011-10-28 | 2013-05-08 | 北京六盛合医药科技有限公司 | 一种治疗慢性支气管炎的药物组合物及其制法 |
CN110507772A (zh) * | 2019-09-22 | 2019-11-29 | 李佳 | 一种治疗慢性支气管炎的中药膏剂及其制备方法 |
-
2020
- 2020-09-23 CN CN202011009537.6A patent/CN114246903B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1628837A (zh) * | 2004-08-30 | 2005-06-22 | 鲁南制药股份有限公司 | 一种治疗冠心病、心绞痛的药物组合物及其制备方法 |
CN103083597A (zh) * | 2011-10-28 | 2013-05-08 | 北京六盛合医药科技有限公司 | 一种治疗慢性支气管炎的药物组合物及其制法 |
CN110507772A (zh) * | 2019-09-22 | 2019-11-29 | 李佳 | 一种治疗慢性支气管炎的中药膏剂及其制备方法 |
Non-Patent Citations (3)
Title |
---|
崔笑.心通颗粒主要医治什么?.百度.2013,第1页第2段. * |
心通颗粒主要医治什么?;崔笑;百度;第1页第2段 * |
胡维勤.《吃对食物 养好肺 精挑细选72种上好的清肺养肺食材,对症调理12种易发的呼吸系统疾病》.2016,第214页. * |
Also Published As
Publication number | Publication date |
---|---|
CN114246903A (zh) | 2022-03-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2450046B1 (en) | A medicinal composition for the treatment of bronchitis and preparation thereof | |
CN106138360A (zh) | 一种中药组合物及其制备方法、应用 | |
CN114246903B (zh) | 心通制剂在制备治疗慢性支气管炎药物中的应用及其制备方法 | |
CN112826889A (zh) | 一种治疗非酒精性脂肪肝病的中药组合物 | |
CN111529608A (zh) | 小儿消积止咳制剂在制备治疗发热证药物中的应用及其制备方法 | |
WO2023109574A1 (zh) | 一种治疗甲状腺癌的中药组合物及其制备方法 | |
CN107412462B (zh) | 一种黄龙咳喘胶囊的制备方法 | |
CN102048841A (zh) | 一种具有催乳作用的中药组合物及其制备工艺 | |
CN103989762B (zh) | 一种清热泻腑止咳化痰的中药组合物及其制备方法 | |
CN112870309A (zh) | 中药组合物在制备治疗或改善胃肠道疾病的药物方面的应用 | |
CN113952419A (zh) | 一种用于慢性肾功能衰竭的药物组合物及制备方法和应用 | |
CN103861041B (zh) | 一种治疗急慢性鼻炎的中药组合物及其制备方法 | |
CN107595870B (zh) | 一种健脑安神的药物组合物、药物制剂及应用和制备方法 | |
CN105362645A (zh) | 一种制备治疗口腔炎症的药物组合物的方法 | |
CN105617319A (zh) | 一种制备治疗急性胆囊炎的中药组合物的方法 | |
CN113876844B (zh) | 一种用于治疗慢性气管炎的纯中药藏药及其制备方法和应用 | |
CN102100814A (zh) | 一种治疗重症哮喘的纳米中药制备及其生产方法 | |
CN113694167B (zh) | 一种治疗脾胃虚弱型萎缩性胃炎的中药组合物及其制备方法 | |
CN105395831A (zh) | 一种治疗口腔炎症的药物组合物 | |
CN105396105A (zh) | 一种制备防治小儿反复感冒的中药组合物的方法 | |
CN115607624A (zh) | 一种中药组合物及其制备方法、用途 | |
CN105031339A (zh) | 一种治疗口腔炎的中药组合物 | |
CN113181297A (zh) | 一种治疗颈椎病的中药组合物及其制备方法 | |
CN112999282A (zh) | 一种用于防治虚证便秘的中药复方制剂及其制备工艺 | |
CN114712489A (zh) | 一种缓解骨关节疼痛组合物及其制备方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |