CN102688291A - 一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 - Google Patents
一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 Download PDFInfo
- Publication number
- CN102688291A CN102688291A CN2012101801205A CN201210180120A CN102688291A CN 102688291 A CN102688291 A CN 102688291A CN 2012101801205 A CN2012101801205 A CN 2012101801205A CN 201210180120 A CN201210180120 A CN 201210180120A CN 102688291 A CN102688291 A CN 102688291A
- Authority
- CN
- China
- Prior art keywords
- herba scutellariae
- scutellariae barbatae
- total flavones
- compositions
- sculellaria barbata
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 235000011949 flavones Nutrition 0.000 title claims abstract description 64
- 229930003944 flavone Natural products 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- -1 flavone compound Chemical class 0.000 title abstract description 10
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 title abstract description 9
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 title abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 52
- 239000011347 resin Substances 0.000 claims abstract description 19
- 229920005989 resin Polymers 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 10
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 7
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 6
- 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 6
- 206010017758 gastric cancer Diseases 0.000 claims abstract description 6
- 201000011549 stomach cancer Diseases 0.000 claims abstract description 6
- 150000002213 flavones Chemical class 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 17
- 239000006228 supernatant Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000006188 syrup Substances 0.000 claims description 14
- 235000020357 syrup Nutrition 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 238000010828 elution Methods 0.000 claims description 11
- 239000003463 adsorbent Substances 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 7
- 230000002421 anti-septic effect Effects 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000012567 medical material Substances 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 5
- 201000008275 breast carcinoma Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 4
- 238000010298 pulverizing process Methods 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 3
- DJSISFGPUUYILV-UHFFFAOYSA-N UNPD161792 Natural products O1C(C(O)=O)C(O)C(O)C(O)C1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-UHFFFAOYSA-N 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- NPLTVGMLNDMOQE-UHFFFAOYSA-N carthamidin Natural products C1=CC(O)=CC=C1C1OC2=CC(O)=C(O)C(O)=C2C(=O)C1 NPLTVGMLNDMOQE-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- 239000008213 purified water Substances 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- DJSISFGPUUYILV-ZFORQUDYSA-N scutellarin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-ZFORQUDYSA-N 0.000 claims description 3
- 229930190376 scutellarin Natural products 0.000 claims description 3
- 230000001954 sterilising effect Effects 0.000 claims description 3
- 238000004659 sterilization and disinfection Methods 0.000 claims description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- 244000099147 Ananas comosus Species 0.000 claims description 2
- 235000007119 Ananas comosus Nutrition 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 240000008790 Musa x paradisiaca Species 0.000 claims description 2
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- 239000007979 citrate buffer Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 2
- 229960003415 propylparaben Drugs 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019202 steviosides Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- PAKISRAZZVIYMX-UHFFFAOYSA-N triazanium 2-hydroxypropane-1,2,3-tricarboxylate 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [NH4+].[NH4+].[NH4+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PAKISRAZZVIYMX-UHFFFAOYSA-N 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims 4
- 125000000185 sucrose group Chemical group 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 201000005202 lung cancer Diseases 0.000 abstract description 3
- 208000020816 lung neoplasm Diseases 0.000 abstract description 3
- 201000007270 liver cancer Diseases 0.000 abstract description 2
- 208000014018 liver neoplasm Diseases 0.000 abstract description 2
- 230000036210 malignancy Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000915604 Scutellaria barbata Species 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 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
- 238000002156 mixing Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 206010003011 Appendicitis Diseases 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- 241000688694 Cheilanthes argentea Species 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000207923 Lamiaceae Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 241001529246 Platymiscium Species 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- 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 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229930002877 anthocyanin Natural products 0.000 description 1
- 235000010208 anthocyanin Nutrition 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 150000004636 anthocyanins Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229930015036 aurone Natural products 0.000 description 1
- 150000001530 aurones Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 150000007946 flavonol Chemical class 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000003453 lung abscess Diseases 0.000 description 1
- 201000007227 lymph node tuberculosis Diseases 0.000 description 1
- 229930014802 neoflavonoid Natural products 0.000 description 1
- 150000002804 neoflavonoids Chemical class 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001047 pyretic effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明涉及一种半枝莲总黄酮组合物及由其为活性成分的口服制剂，以及二者的制备方法。每1重量份的半枝莲总黄酮组合物包括30-50重量份的半枝莲与180-500重量份的50-80%的乙醇、3-50重量份的大孔吸附树脂、100-300重量份60-80%的乙醇经过制备而成。本发明的半枝莲总黄酮组合物特别适合制成各种口服制剂，是治疗胃癌、肝癌、肺癌、乳腺癌等恶性肿瘤的理想用药，总有效率达到88.1%。
Description
技术领域
本发明属于含有来自传统草药的未完全确定结构的药物组合物，具体涉及一种半枝莲总黄酮组合物及由其为活性成分的口服制剂，以及二者的制备方法。
背景技术
半枝莲总黄酮是指半枝莲(Scutellaria barbata D.Don)中的黄酮类化合物的总和，可能包括双氢黄（醇）、异黄酮、双黄酮、黄烷醇、查尔酮、橙酮、花色苷及新黄酮类等。当采用不同的分离和富集技术时，得到物质成分并不完全相同的半枝莲总黄酮组合物，上述组合物会表现出不同药物活性。目前，尚未有半枝莲总黄酮制剂上市，下述专利中公开了几种半枝莲总黄酮。
专利CN200910074686公开了一种半枝莲总黄酮，其用途为抗痴呆病，制法为分别经过20倍量、10倍量两次醇提，再对回收乙醇后的残留液经酸沉（PH2），制得半枝莲总黄酮。专利CN200710047257公开了一种能抗流感病毒的半枝莲总黄酮，制法为50-80%的酒精提取、乙醚萃取，水相上D101大孔树脂，用水和酒精梯度洗脱，收集，该半枝莲总黄酮的主要组分为芹菜素。专利CN200710023766公开了一种半枝莲总黄酮的注射液，制法为采用20-50%的低浓度乙醇处理，药渣用碱处理，而后采用常规方法制得注射液。专利CN200410088833公开了另外一种半枝莲总黄酮，其制法为先经过水提，再酸处理，再用大孔吸附树脂处理，大孔树脂的洗脱液分别为水和高浓度85%以上的乙醇。
显而易见，由于工艺的不完全一致，上述半枝莲总黄酮表现出不同的药物活性，因而继续优化工艺进而找到疗效更高、作用广泛的半枝莲总黄酮具有重要意义。
发明内容
本发明的目的是提供一种用于治疗癌症的半枝莲总黄酮组合物，特别是适合制备口服制剂的半枝莲总黄酮组合物。具体技术方案如下：
本发明的半枝莲总黄酮组合物，其每1重量份的所述组合物包括如下重量份原料制备而成：
半枝莲30-50 50-80%的乙醇180-500
大孔吸附树脂3-50 60-80%的乙醇100-300。
本发明的半枝莲(Scutellaria barbata D.Don)为唇形科黄芬属植物半枝莲的全草，别名通经草、紫连草、并头草，牙刷草等。主要产于江苏、浙江、贵州、福建、广东、云南等省区。目前从半枝莲中已经分离出了一些化合物，主要是总黄酮类、生物碱、甾体以及酚类等。
本发明的半枝莲总黄酮组合物，其中含野黄芩苷的重量百分比为1-5%，由于植物药物的自身特点，本发明并不限定半枝莲总黄酮组合物的药物活性是以野黄芩苷为代表，与此相反，本发明的半枝莲总黄酮组合物是整体发挥疗效。
本发明的半枝莲总黄酮组合物，为了便于制备口服制剂，一般是无水的，但在含水量为0.1-10%，甚至于更高，均在本发明的保护范围之内。
本发明提供的一种半枝莲总黄酮组合物的制备方法包括如下步骤：
取半枝莲药材粉碎，用50-80%的乙醇浸泡1-3h后，热回流提取2-3h，提取2次，合并滤液，减压浓缩滤液至药材量的3倍，离心，得第一上清液；
取离心后的第一上清液用盐酸调节pH至2-4，离心，得第二上清液，备用；
称取大孔吸附树脂，经预处理后，装柱；
将第二上清液过大孔树脂柱吸附，先用水进行洗脱，再以60-80%的乙醇洗脱，收集60-80%的乙醇洗脱部分，减压浓缩，干燥，即得半枝莲总黄酮组合物。
本发明的大孔吸附树脂优选AB-8、D101两种型号。
本发明的半枝莲总黄酮组合物最适合用于制备以其为活性成分的口服制剂，特别包括口服溶液、糖浆剂、片剂、胶囊、颗粒剂等，当然还可选自中国药典中介绍的其他口服制剂。
本发明的半枝莲总黄酮组合物最适合制备糖浆剂或口服溶液，每1000ml糖浆剂或口服溶液包括如下重量份原料制成的水溶液：
半枝莲总黄酮50~300g 甜味剂10~500g
芳香剂1~5g 防腐剂0.1~3g pH调节剂0.1-10g。
上述pH调节剂的用量以调节pH值在2-7为准。
本发明的甜味剂选自但不限于蔗糖、阿司帕坦、甜菊糖苷、山梨醇；芳香剂选自但不限于香蕉香精、橘子香精、菠萝香精、柠檬香精、草莓香精；防腐剂选自但不限于对羟苯甲酸乙酯、羟苯甲酸丙酯、山梨酸钾、苯甲酸、苯甲酸钠；pH调节剂选自但不限于稀盐酸、枸橼酸、柠檬酸-柠檬酸铵缓冲溶液、磷酸盐缓冲液。
下面是半枝莲总黄酮口服溶液或糖浆的制备方法的详细步骤：
A首先制得半枝莲总黄酮
取半枝莲药材粉碎，用6-10倍量的50-80%的乙醇浸泡1-3h后，热回流提取2-3h，提取2次，合并滤液，减压浓缩至药材量的3倍，离心，取上清液用盐酸调节pH至2-4，离心，收集上清液，备用；称取大孔吸附树脂，经预处理后，装柱，树脂与生药的质量比为1：2-10；将上述上清液过大孔树脂柱吸附，先用水进行洗脱，洗脱至无色后，再以71-80%的乙醇洗脱至无色，收集71-80%的乙醇洗脱部分，减压浓缩，干燥，即得半枝莲总黄酮组合物；
B半枝莲总黄酮口服溶液或糖浆的制备
（1）称取处方量的原辅料；
（2）将称量好的半枝莲总黄酮、甜味剂分别加入到适量纯化水中，搅拌使其完全溶解；
（3）将称量好的的芳香剂和防腐剂分别加适宜溶剂溶解后，加入到药液中，充分搅拌，使其混合均匀并煮沸；
（4）所得的药液用pH调节剂调整pH值至4-7，加水至全量，搅匀，滤过。
（5）取滤过后的药液进行检验，分装，灭菌，即得。
本发明的半枝莲总黄酮组合物在治疗胃癌、肝癌、肺癌、乳腺癌等恶性肿瘤药物中的应用中，疗效显著。
本发明产品符合中医理论，该药性寒，味苦，归肺、肝、肾、胃经。具有清热解毒、活血祛瘀、消肿止痛、抗癌等功效。用于治疗热毒痈肿、咽喉疼痛、肺痈、肠痈、瘰疬、毒蛇咬伤、跌打损伤、及癌症等疾病。现代药理学研究表明，半枝莲对肉瘤180、艾氏腹水癌、脑瘤22等多种肿瘤细胞均有抑制作用，其中半枝莲对JTc-26瘤细胞体外抑制更是率达100%。即使是对治疗乏术的晚期肿瘤，亦有改善症状、抑制肿瘤增殖和延长患者生命的作用。除抗癌作用外，半枝莲还有抑菌、利尿、止咳、平喘等多种药理作用。在临床上，半枝莲可治疗肝癌、肺癌、乳腺癌、绒毛膜癌等。
本发明有益效果为，半枝莲总黄酮组合物特别时候制成各种口服制剂，动物实验观察表明，吸收利用度好，是治疗胃癌、肝癌、肺癌、乳腺癌等恶性肿瘤的理想用药，不良反应小，疗效好，经济安全。此外本发明的口服溶液或糖浆患者依从性好，特别适合于儿童、老年人和吞咽困难的患者服用。同时本发明的制备方法，工艺简单，适合于工业化生产。
下面通过临床应用对本发明做进一步说明
试验药物为实施例2的糖浆剂；
对照药物为半枝莲片（武汉九鼎药业有限公司）
试验人数14人分为对照组和试验组
结果对照组的有效率达到88.1%；试验组的有效率为53.4%，典型病例如下：
典型病例1
某胃癌患者，28岁，胃癌中晚期，连续服用本发明糖浆剂6个疗程，每个疗程1个月，1个疗程即显效，6个疗程后，痊愈。
典型病例2
某肝癌患者，69岁，早期肝癌，连续服用本发明糖浆剂3个疗程，每个疗程1个月，延长生命2年。
典型病例3
某肺癌患者，女，晚期肺癌，连续服用本发明糖浆剂6个疗程，每个疗程1个月，延长生命1.5年。
典型病例4
某乳腺癌晚期患者，服用其他抗癌药物效果不佳，连续服用本发明糖浆剂3个疗程，每个疗程1个月，3个月后基本痊愈。
下面结合具体实施例对本发明作进一步的说明，但不限于此。
具体实施方式
实施例1半枝莲总黄酮的制备
取半枝莲药材5kg，粉碎，用10倍量的70%的乙醇浸泡2h后，热回流提取3h，提取2次，合并滤液，减压浓缩至药材量的3倍，离心，取上清液用盐酸调节pH至2，离心，收集上清液，备用。称取D101型大孔吸附树脂1kg，经预处理后，装柱。将上述上清液过大孔树脂柱吸附，先水进行洗脱，洗脱至无色后，再以70%以上的乙醇洗脱至无色，收集70%以上的乙醇洗脱部分，减压浓缩，干燥，即得半枝莲总黄酮。
实施例2半枝莲总黄酮口服溶液或糖浆的制备
每1000ml半枝莲总黄酮口服溶液或糖浆中各种组分的含量如下：
具体制备方法如下：
将半枝莲总黄酮、遮糖分别加入适量水中溶解，煮沸；另将苯甲酸和草莓香精分别加水溶解后，加入到药液中，搅匀并煮沸；加入用稀盐酸溶液调节pH值，加纯化水至1000ml，搅匀，过滤，检验，分装，灭菌，即得。
实施例3半枝莲总黄酮片
采用常规技术，取半枝莲总黄酮组合物细粉，加入淀粉，再加入10%淀粉浆适量制成软材，制粒，加入微晶纤维素、硬脂酸镁充分混匀，压片，即得。
实施例4半枝莲总黄酮胶囊
采用常规技术，取半枝莲总黄酮细粉，加入微晶纤维素、淀粉，用稀乙醇制粒，整粒后，加入硬脂酸镁适量，充分混匀，填入胶囊，制得1000粒。
以上所述实施例仅仅是本发明的优选实施方式进行描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案作出的各种变形和改进，均应落入本发明的权利要求书确定的保护范围内。
Claims (9)
1.一种半枝莲总黄酮组合物，其特征在于，每1重量份的所述组合物包括如下重量份原料制备而成：
半枝莲30-50 50-80%的乙醇180-500
大孔吸附树脂3-50 60-80%的乙醇100-300。
2.如权利要求1所述的半枝莲总黄酮组合物，其特征在于所述组合物中含野黄芩苷的重量百分比为1-5%。
3.如权利要求1所述的半枝莲总黄酮组合物，其特征在于所述组合物中含水量为0.1-10%。
4.如权利要求1-3所述的任一半枝莲总黄酮组合物的制备方法，其特征在于包括如下步骤：
取半枝莲药材粉碎，用50~80%的乙醇浸泡1-3h后，热回流提取2-3h，提取2次，合并滤液，减压浓缩滤液至药材量的3倍，离心，得第一上清液；
取离心后的第一上清液用盐酸调节pH至2-4，离心，得第二上清液，备用；
称取大孔吸附树脂，经预处理后，装柱；
将第二上清液过大孔树脂柱吸附，先用水进行洗脱，再以60-80%的乙醇洗脱，收集60-80%的乙醇洗脱部分，减压浓缩，干燥，即得半枝莲总黄酮组合物。
5.以权利要求1-3所述的任一半枝莲总黄酮组合物为活性成分的口服固体制剂，其特征在于：所述固体制剂包括口服溶液、糖浆剂、片剂、胶囊、颗粒剂。
6.如权利要求5所述口服固体制剂，其特征在于，所述固体制剂为糖浆剂或口服溶液，每1000ml糖浆剂或口服溶液包括如下重量份原料制成的水溶液：
半枝莲总黄酮50~300g 甜味剂10~500g
芳香剂1~5g 防腐剂0.1~3g pH调节剂0.1-10g。
7.如权利要求6所述的口服溶液或糖浆，其特征在于所述甜味剂选自蔗糖、阿司帕坦、甜菊糖苷、山梨醇；所述芳香剂选自香蕉香精、橘子香精、菠萝香精、柠檬香精、草莓香精；所述防腐剂选自对羟苯甲酸乙酯、羟苯甲酸丙酯、山梨酸钾、苯甲酸、苯甲酸钠；所述pH调节剂选自稀盐酸、枸橼酸、柠檬酸-柠檬酸铵缓冲溶液、磷酸盐缓冲液。
8.如权利要求6所述的半枝莲总黄酮口服溶液或糖浆的制备方法，其特征在于包括以下步骤：
A半枝莲总黄酮的制备
取半枝莲药材粉碎，用6-10倍量的50-80%的乙醇浸泡1-3h后，热回流提取2-3h，提取2次，合并滤液，减压浓缩至药材量的3倍，离心，取上清液用盐酸调节pH至2-4，离心，收集上清液，备用；称取大孔吸附树脂，经预处理后，装柱，树脂与生药的质量比为1：2-10；将上述上清液过大孔树脂柱吸附，先用水进行洗脱，洗脱至无色后，再以71-80%的乙醇洗脱至无色，收集71-80%的乙醇洗脱部分，减压浓缩，干燥，即得半枝莲总黄酮组合物；
B半枝莲总黄酮口服溶液或糖浆的制备
（1）称取处方量的原辅料；
（2）将称量好的半枝莲总黄酮、甜味剂分别加入到适量纯化水中，搅拌使其完全溶解；
（3）将称量好的的芳香剂和防腐剂分别加适宜溶剂溶解后，加入到药液中，充分搅拌，使其混合均匀并煮沸；
（4）所得的药液用pH调节剂调整pH值至4-7，加水至全量，搅匀，滤过。
（5）取滤过后的药液进行检验，分装，灭菌，即得。
9.如权利要求1所述半枝莲总黄酮组合物在治疗胃癌、肝癌、肺癌、乳腺癌等恶性肿瘤药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210180120.5A CN102688291B (zh) | 2012-06-01 | 2012-06-01 | 一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210180120.5A CN102688291B (zh) | 2012-06-01 | 2012-06-01 | 一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102688291A true CN102688291A (zh) | 2012-09-26 |
| CN102688291B CN102688291B (zh) | 2014-07-09 |
Family
ID=46854136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210180120.5A Active CN102688291B (zh) | 2012-06-01 | 2012-06-01 | 一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102688291B (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104758356A (zh) * | 2015-04-01 | 2015-07-08 | 辽宁中医药大学 | 一种抗肝癌中药组合物 |
| CN104758356B (zh) * | 2015-04-01 | 2018-08-31 | 辽宁中医药大学 | 一种抗肝癌中药组合物 |
| CN111195286A (zh) * | 2020-03-28 | 2020-05-26 | 新乡医学院 | 一种抗肿瘤组合物 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726958A (zh) * | 2004-07-26 | 2006-02-01 | 天津药物研究院 | 一种用于治疗流感病毒感染的中药制剂及其制备方法 |
| CN1769292A (zh) * | 2004-11-05 | 2006-05-10 | 王英锋 | 一种半枝莲总黄酮的制备方法和质量控制方法 |
| CN1961898A (zh) * | 2005-11-10 | 2007-05-16 | 黄振华 | 一种复方半枝莲抗肿瘤药物组合物及其制备方法 |
| CN101569658A (zh) * | 2009-06-04 | 2009-11-04 | 承德医学院中药研究所 | 半枝莲总黄酮作为制备抗痴呆病药的应用 |
| CN101623326A (zh) * | 2009-07-30 | 2010-01-13 | 扬州大学 | 一种半枝莲制剂及其制备方法 |
-
2012
- 2012-06-01 CN CN201210180120.5A patent/CN102688291B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726958A (zh) * | 2004-07-26 | 2006-02-01 | 天津药物研究院 | 一种用于治疗流感病毒感染的中药制剂及其制备方法 |
| CN1769292A (zh) * | 2004-11-05 | 2006-05-10 | 王英锋 | 一种半枝莲总黄酮的制备方法和质量控制方法 |
| CN1961898A (zh) * | 2005-11-10 | 2007-05-16 | 黄振华 | 一种复方半枝莲抗肿瘤药物组合物及其制备方法 |
| CN101569658A (zh) * | 2009-06-04 | 2009-11-04 | 承德医学院中药研究所 | 半枝莲总黄酮作为制备抗痴呆病药的应用 |
| CN101623326A (zh) * | 2009-07-30 | 2010-01-13 | 扬州大学 | 一种半枝莲制剂及其制备方法 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104758356A (zh) * | 2015-04-01 | 2015-07-08 | 辽宁中医药大学 | 一种抗肝癌中药组合物 |
| CN104758356B (zh) * | 2015-04-01 | 2018-08-31 | 辽宁中医药大学 | 一种抗肝癌中药组合物 |
| CN111195286A (zh) * | 2020-03-28 | 2020-05-26 | 新乡医学院 | 一种抗肿瘤组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102688291B (zh) | 2014-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102114102B (zh) | 一种具有保肝利胆作用的中药提取物混合制剂及其应用 | |
| CN105012452A (zh) | 黄皮叶的新用途 | |
| CN104666373A (zh) | 东革阿里新用途 | |
| CN104547151A (zh) | 一种中药提取物及制备方法 | |
| CN102302673B (zh) | 一种预防和治疗糖尿病肾病的中药复方制剂 | |
| WO2004054596A1 (fr) | Medicament contenant un extrait d'epimedium et destine au traitement de l'hyperplasie prostatique et de la prostatite | |
| CN102228547B (zh) | 一种中药组合物在制备治疗胰腺炎和/或胆囊炎药物中的应用 | |
| CN100477996C (zh) | 虎眼万年青提取物及其制备方法、药物组合物以及用途 | |
| CN101757391B (zh) | 一种治疗心血管疾病的药物组合物及其制备方法和用途 | |
| CN101564466A (zh) | 一种含有抗肿瘤活性成分的中药有效部位组合物及其制备方法与应用 | |
| CN101390970B (zh) | 一种治疗乙肝的中药及其制备方法 | |
| CN1973853B (zh) | 一种止血镇痛的药物组合物及其制备方法 | |
| CN101411779B (zh) | 一种治疗肝癌的中药有效部位组合物及其制备方法 | |
| CN102688291B (zh) | 一种半枝莲总黄酮组合物及由其制备的口服制剂和制法 | |
| WO2011016652A2 (ko) | 항치루 조성물 및 그 제조 방법 | |
| CN102188483B (zh) | 一种治疗咽喉炎的提取物及其制备方法 | |
| CN103655651A (zh) | 一种灯台叶浸膏和提取物及其制备方法 | |
| CN101199652B (zh) | 治疗急性、亚急性湿疹的药物及其制备方法 | |
| CN103432386B (zh) | 一种治疗咳嗽的中药制剂及其制备方法 | |
| CN102755519B (zh) | 葛根葛花抗口腔溃疡颗粒及其制备方法 | |
| CN101269123A (zh) | 消渴降糖胶囊二次开发的新工艺 | |
| CN100355440C (zh) | 治疗ⅱ型糖尿病、降低血糖的中药复方制剂及其制备方法 | |
| CN101991722B (zh) | 一种石歧外感中药胶囊 | |
| CN102429946B (zh) | 一种用于制备抗流感病毒药物的中药组合物 | |
| CN114601807B (zh) | 一种贝草清肺浓缩丸的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HEILONGJIANG BAITONG CHILDREN'S MEDICAL RESEARCH C Free format text: FORMER OWNER: KANGYANG RUNHE (BEIJING) MEDICAL TECHNOLOGY CO., LTD. Effective date: 20150215 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100073 FENGTAI, BEIJING TO: 150025 HARBIN, HEILONGJIANG PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150215 Address after: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee after: HEILONGJIANG BAITONG CHILDREN MEDICINE RESEARCH CO.,LTD. Address before: 100073 Beijing city Fengtai District Lize Road No. 1 Building No. 9 Hospital No. 104 (Taiping Bridge enterprises centralized office area) Patentee before: KANGYANG RUNHE (BEIJING) MEDICAL TECHNOLOGY CO.,LTD. |
|
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee after: Heilongjiang children doctor biological medicine science and Technology Co.,Ltd. Address before: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee before: HEILONGJIANG BAITONG CHILDREN MEDICINE RESEARCH CO.,LTD. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160612 Address after: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai Lunanli people biopharmaceutical research center of life medicine venture building, No. 315 Patentee after: Heilongjiang Dong doctor children bio Pharmaceutical Co.,Ltd. Address before: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee before: Heilongjiang children doctor biological medicine science and Technology Co.,Ltd. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160630 Address after: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee after: HEILONGJIANG CHILDREN DOCTOR CHILDREN BIOLOGY PHARMACY Co.,Ltd. Address before: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee before: Heilongjiang children doctor biological medicine science and Technology Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200820 Address after: No.2, 1st floor, unit 6, no.508-2, Xinyang Road, Daoli District, Harbin City, Heilongjiang Province Patentee after: HARBIN KUNMENG PHARMACEUTICAL TECHNOLOGY Co.,Ltd. Address before: 150025 Heilongjiang city of Harbin province Shenyang Limin Development Zone, East Street Zhuhai people Lunanli biomedical research center of life medicine venture building, No. 315 Patentee before: HEILONGJIANG CHILDREN DOCTOR CHILDREN BIOLOGY PHARMACY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220711 Address after: 150000 No. 315, life medicine entrepreneurship building, Limin biomedical research and development center, East Shenyang Street and South Zhuhai Road, Limin Development Zone, Harbin, Heilongjiang Province Patentee after: HEILONGJIANG CHILDREN DOCTOR CHILDREN BIOLOGY PHARMACY Co.,Ltd. Address before: 150070 No.2, 1st floor, unit 6, no.508-2, Xinyang Road, Daoli District, Harbin City, Heilongjiang Province Patentee before: HARBIN KUNMENG PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |