CN103585291B - Application of herba delphinii extract in preparation of drugs treating AIDS - Google Patents
Application of herba delphinii extract in preparation of drugs treating AIDS Download PDFInfo
- Publication number
- CN103585291B CN103585291B CN201310525344.XA CN201310525344A CN103585291B CN 103585291 B CN103585291 B CN 103585291B CN 201310525344 A CN201310525344 A CN 201310525344A CN 103585291 B CN103585291 B CN 103585291B
- Authority
- CN
- China
- Prior art keywords
- extract
- herba delphinii
- delphinii grandiflori
- hair herba
- exhibition
- 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.)
- Expired - Fee Related
Links
- 239000000284 extract Substances 0.000 title claims abstract description 132
- 239000003814 drug Substances 0.000 title claims abstract description 63
- 208000030507 AIDS Diseases 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 229940079593 drug Drugs 0.000 title claims abstract description 25
- 239000011347 resin Substances 0.000 claims abstract description 37
- 229920005989 resin Polymers 0.000 claims abstract description 37
- 238000001179 sorption measurement Methods 0.000 claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 72
- 239000007788 liquid Substances 0.000 claims description 38
- 238000000605 extraction Methods 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 239000003463 adsorbent Substances 0.000 claims description 18
- 230000001476 alcoholic effect Effects 0.000 claims description 18
- 239000012141 concentrate Substances 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 18
- 239000003480 eluent Substances 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 12
- -1 reflux Substances 0.000 claims description 11
- 230000002879 macerating effect Effects 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims 2
- 238000000746 purification Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 31
- 241000725303 Human immunodeficiency virus Species 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 241000700605 Viruses Species 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 208000011580 syndromic disease Diseases 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 206010022000 influenza Diseases 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 11
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- 206010035664 Pneumonia Diseases 0.000 description 6
- 241000725643 Respiratory syncytial virus Species 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 231100000614 poison Toxicity 0.000 description 6
- 241000712461 unidentified influenza virus Species 0.000 description 6
- 241000282693 Cercopithecidae Species 0.000 description 5
- 239000004378 Glycyrrhizin Substances 0.000 description 5
- 108010021119 Trichosanthin Proteins 0.000 description 5
- 210000004970 cd4 cell Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 5
- 229960004949 glycyrrhizic acid Drugs 0.000 description 5
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 5
- 235000019410 glycyrrhizin Nutrition 0.000 description 5
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- BTXNYTINYBABQR-UHFFFAOYSA-N hypericin Chemical compound C12=C(O)C=C(O)C(C(C=3C(O)=CC(C)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 BTXNYTINYBABQR-UHFFFAOYSA-N 0.000 description 4
- 229940005608 hypericin Drugs 0.000 description 4
- PHOKTTKFQUYZPI-UHFFFAOYSA-N hypericin Natural products Cc1cc(O)c2c3C(=O)C(=Cc4c(O)c5c(O)cc(O)c6c7C(=O)C(=Cc8c(C)c1c2c(c78)c(c34)c56)O)O PHOKTTKFQUYZPI-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002574 poison Substances 0.000 description 4
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 241000714177 Murine leukemia virus Species 0.000 description 3
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 3
- 108090000829 Ribosome Inactivating Proteins Proteins 0.000 description 3
- 241000713311 Simian immunodeficiency virus Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000002155 anti-virotic effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 208000002672 hepatitis B Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 208000007778 simian acquired immunodeficiency syndrome Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000208340 Araliaceae Species 0.000 description 2
- 235000010894 Artemisia argyi Nutrition 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- 241000709673 Coxsackievirus B4 Species 0.000 description 2
- 241000219104 Cucurbitaceae Species 0.000 description 2
- 241001337079 Delphinium kamaonense Species 0.000 description 2
- 235000017309 Hypericum perforatum Nutrition 0.000 description 2
- 244000302512 Momordica charantia Species 0.000 description 2
- 235000009811 Momordica charantia Nutrition 0.000 description 2
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 description 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
- 235000003140 Panax quinquefolius Nutrition 0.000 description 2
- 240000007643 Phytolacca americana Species 0.000 description 2
- 235000009074 Phytolacca americana Nutrition 0.000 description 2
- 241000218201 Ranunculaceae Species 0.000 description 2
- 206010041660 Splenomegaly Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 244000030166 artemisia Species 0.000 description 2
- FXNFHKRTJBSTCS-UHFFFAOYSA-N baicalein Chemical compound C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 description 2
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin 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=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 description 2
- 229960003321 baicalin Drugs 0.000 description 2
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000003748 differential diagnosis Methods 0.000 description 2
- 208000001848 dysentery Diseases 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- 101150008103 hal gene Proteins 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 239000008517 radix Trichosanthis Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 239000009254 shuang-huang-lian Substances 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- NIDRYBLTWYFCFV-FMTVUPSXSA-N (+)-calanolide A Chemical compound C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-FMTVUPSXSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000272522 Anas Species 0.000 description 1
- NIDRYBLTWYFCFV-IUUKEHGRSA-N Calanolide A Natural products C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-IUUKEHGRSA-N 0.000 description 1
- 241000871287 Calophyllum lanigerum Species 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000725618 Duck hepatitis B virus Species 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 208000015220 Febrile disease Diseases 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 240000008917 Glycyrrhiza uralensis Species 0.000 description 1
- 235000000554 Glycyrrhiza uralensis Nutrition 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000891326 Homo sapiens Treacle protein Proteins 0.000 description 1
- 239000009636 Huang Qi Substances 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- 206010021718 Induced labour Diseases 0.000 description 1
- 241001500351 Influenzavirus A Species 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001007959 Mucuna birdwoodiana Species 0.000 description 1
- OSKIPPQETUTOMW-YHLOVPAPSA-N N-[(2R,3R,4R,5S,6R)-5-[(2S,3R,4R,5S,6R)-3-Acetamido-5-[(2R,3S,4S,5R,6R)-4-[(2R,3S,4S,5S,6R)-3-[(2S,3S,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2S,3S,4S,5R,6R)-6-[[(2S,3S,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxymethyl]-3,5-dihydroxy-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxymethyl]-3,5-dihydroxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,4-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O[C@@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO[C@@H]3[C@H]([C@@H](O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)O3)O)O2)O)[C@@H](CO)O1 OSKIPPQETUTOMW-YHLOVPAPSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108050001408 Profilin Proteins 0.000 description 1
- 102000011195 Profilin Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 231100000645 Reed–Muench method Toxicity 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 240000006023 Trichosanthes kirilowii Species 0.000 description 1
- 235000009818 Trichosanthes kirilowii Nutrition 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- NIDRYBLTWYFCFV-UHFFFAOYSA-N calanolide F Natural products C1=CC(C)(C)OC2=C1C(OC(C)C(C)C1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-UHFFFAOYSA-N 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000003771 laboratory diagnosis Methods 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000031864 metaphase Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 229940100050 virazole Drugs 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Abstract
The invention relates to new application of a herba delphinii extract in preparation of drugs treating AIDS. The herba delphinii extract is prepared by: extracting herba delphinii, and conducting macroporous adsorption resin purification twice. The herba delphinii extract provided by the invention is of great significance in preparing drugs treating AIDS.
Description
Technical field
The invention belongs to biomedicine field, relate to the application of a kind of Chinese medicinal material extract in preparation treatment AIDS-treating medicine, specifically relate to a kind of mao Herba delphinii grandiflori extract of opening up and preparing the application in treatment AIDS-treating medicine.
Background technology
Acquired immune deficiency syndrome (AIDS) is the new virus sexually transmitted disease found in 1981, and the traditional Chinese medical science past is not on the books to it.The traditional Chinese medical science is dialectical to acquired immune deficiency syndrome (AIDS), thinks that acquired immune deficiency syndrome (AIDS) belongs to epidemic disease category.The cause of disease is the scorchingly hot heresy invasion and attack of epidemic disease, deficiency of vital QI and causing.Pathogenesis is mainly weakened defensive QI, and yang-energy damages, and internal organs are got involved, and causes that the deficiency of the lung is insufficiency of the spleen suffers from a deficiency of the kidney, secondary infection.Thermal burn venation, coagulation of QI-blood, Xing Cheng mass in the abdomen lump tumor.
Syndrome Differentiation of Chinese Medicine " card ": mainly distinguish ebb and flow between pathogen and vital QI and deficiency syndrome excess syndrome.HIV (human immunodeficiency virus) is evil poison, and the change of disease in evil poison enters, the dynamic change of just resisting with the heresy of body healthy energy is advancing of disease process.Infect early stage based on the domination of pathogen, mid-term " causes void because of real ", late period " excess caused by deficiency ".The acquired immune deficiency syndrome (AIDS) state of an illness copies changeable, and acquired immune deficiency syndrome (AIDS) and secondary infection thereof all can be formed " disease ", and has difference " type " and " phase ".The traditional Chinese medical science has dialectical differential diagnosis of diseases to acquired immune deficiency syndrome (AIDS), the typing different diagnosis and treatment project such as by stages.
The Chinese medicine of acquired immune deficiency syndrome (AIDS) still belongs to conceptual phase at present, at home and abroad there is no at present generally acknowledged curative effect certainly go through produce AIDS virus resisting Chinese medicine or Chinese medicine monomer compound.AIDS virus resisting plant amedica and Chinese medicine research mainly divide 3 kinds of approach, and the AIDS virus resisting Chinese medicinal plant medicine that smoking set obtains and composition thereof, some is in clinic trial.
Since HIV (human immunodeficiency virus) finds, use HIV (human immunodeficiency virus) cell culture and reverse transcriptase in the world, the ill vitro test method such as protease and intergrase, while extensive SCREENED COMPOUND, also plant and Chinese herbal medicine extract and composition thereof is screened in a large number, also studied some compound Chinese medicinal preparation, find the active drug of inhibiting HIV in vitro, the viremia of the suppressed simian immunodeficiency virus had (SIV) infected monkey.Some is in clinic trial, not yet clear and definite effect.
China removes Africa treatment AIDS patients from 1987 Nian Pai combination of Chinese and Western medicine medical teams.Domestic before 2002, lack specially good effect Anti-AIDS Drugs, Chinese and western medicine, combines with dialectical to AIDS patients differential diagnosis of diseases according to theory of Chinese medical science clinical, with heat-clearing and toxic substances removing, strengthening the body resistance, or removing heat from blood the kidney invigorating, the rule for the treatment of such as blood circulation promoting and blood stasis dispelling, by the property of Chinese materia medica, select Chinese medicine, prescribed treatment.By clinical practice, think that some Medical Complex Prescription in Treating AIDS can improve symptom, mitigate the disease.In recent years to the AIDS patients that laboratory diagnosis is made a definite diagnosis, adopt treatment by Chinese herbs, if matched group, at treatments period, periodic detection blood viral charge (HIV-RNA) and cd4 cell level, evaluation effect.There is report to improve symptom, improve immunity, mostly still in clinical verification.Enter clinical AntiHIV1 RT activity single medicinal material or plant amedica and Chinese medicine compound as follows:
Glycyrrhizin: glycyrrhizin (glycyrrhizin, GL) be the glycyrrhizin that glycyrrhiza uralensis fisch (Glycyrrhiza glabra L) extracts, there is broad-spectrum disease resistance toxic action, vitro inhibition HIV1-RT, HIV cell fusion is suppressed in cell culture, also resisiting influenza virus and SARS virus, the dead and pneumonopathy change of the pneumonia that experiment in vivo proves to protect influenza infection mice to cause; The CCl of protection mice
4toxic liver injury; Induce gamma interferon; There is parahormone effect.Japan's its intravenous administrations chronic hepatitis B conventional, also once tried out treatment AIDS patients, can suppress serum HIV-1-P24 antigen, raised cd4 cell.Lv Weibai professor 1988-1992 can treat AIDS patients African Tanzania application glycyrrhizin oral formulations gram Chinese mugwort can improve symptom, and cd4 cell slightly rises.Its effect is not yet verified.
Trichosanthin: trichosanthin (Trichosanthin, TCS, GLQ223, Q material) belong to Cucurbitaceae (Cucurbitaceae) for Chinese medicine Fructus Trichosanthis (Trichosanthes kirilowii), the main Chinese medicine ingredients of China's Chinese medicine compound for miscarrying among the people is Fructus Trichosanthis, the effective ingredient of China scientist isolation identification device antiearly pregnancy and induced labor is trichosanthin, molecular weight is 27kD, one, secondary structure and three dimensional structure are understood fully completely, for the toxalbumin of Profilin synthesis, ribosome inactivating protein (the Ribosome Inactivating Protein of strand, RIP).The U.S. is when screening anti-HIV-1 medicines, find that it suppresses HIV-1 cell fusion in lymphocyte is cultivated, thereafter find P24 antigen and the RNA of HIV-1 in mononuclear phagocyte is cultivated, blood plasma HIV-1 can be suppressed in the intravenous injection of 3 simian acquired immunodeficiency syndrome virus (SIV) infected monkeys.The U.S. uses intravenous administrations AIDS patients in forest farm, and HIV-1-P24 antigen in the T lymphocyte that peripheral blood HIV-1 can be suppressed to infect and mononuclear phagocyte, makes CD4/ CD8 ratio slightly raise.Due to anaphylactic reaction can be caused dead, neurovirulent Mental Subnormality and nephrotoxicity reaction, clinical experiment stops.From Radix Trichosanthis, isolate other albumen TAP29 in recent years, molecular weight, at 29 kD, also have the effect suppressing HIV-1, but toxicity is less, not in clinic trial.In addition the bitter melon protein of Fructus Momordicae charantiae (MOmordica charantia) and the Radix Phytolaccae albumen (Pokeweed protein) etc. of Radix Phytolaccae (Phytolacca americana) have the effect suppressing HIV.
Hypericin: plant Herba Hyperici Monogyni (St. John Wort, Hypericum perforatum) its extract for treating depression of folk tradition, the active component proposed from flower is hypericin (hypericin), it is the multi-ring dimerization anthraquinone analog compound of aromatic series, for anti-depression drug, complete synthesis.Hypericin has multiple antiviral activity, in cell culture, suppress HIV, and its mechanism of action is undressing of blocking virus, and assembling and release, the effect of killing the virus, by blood brain barrier.Murine leukemia virus can be suppressed in cell culture to breed.The splenomegaly that murine leukemia virus infecting mouse causes can be suppressed in vivo, duck hepatitis B virus infection Sanguis Anas domestica also can be suppressed to ask viral DNA, and have broad spectrum antibiotic active.Once in treatment on probation of clinical I/II phase HIV sufferers, test had been stopped because there being light sensitization.
1992 year report the native compound that from Malaysian rainforest plant Calophyllum lanigerum be separated dextrorotation lane element A: dextrorotation lane element A(+Calanolide A), Mus coumarin kind compound, suppress HIV1-RT, but invalid to HIV-2.Belong to non-nucleoside HIV1-RT inhibitor, in cell culture, multi-to-multi lives in the responsive and drug resistance HIV-1 of the AZT of clinical separation effectively, and and AZT, NVP have synergism.In HIV hollow fiber pipe Mice Body, prove there is AIDS virus resisting effect in experimental model (HIV hollow fiber mouse model), can drug effect be strengthened with AZT use in conjunction.Complete synthesis, having carried out its clinical trial of I-II proves there is the therapeutic effect suppressing HIV-1 to infect, and toxicity is little, and side effect is light, has headache and inappetence etc., effective with AZT drug combination.Be the single plant component uniquely entering II phase clinical experiment at present, observing in checking curative effect, not yet ratify to produce.
Herba Sidae Rhombifoliae soup: Herba Sidae Rhombifoliae soup (Radix Bupleuri, Radix Ginseng, the Rhizoma Pinelliae, Radix Scutellariae, Radix Glycyrrhizae, Rhizoma Zingiberis Recens, Fructus Jujubae)
It is Zhang Zhongjing Treatise on Febrile Diseases side.Hepatitis B is treated with it by Japan, finds that it suppresses HIV in cell culture.The U.S. is used for the treatment of numerical example AIDS patients clinical, can reduce blood-serum P 24 antigen.We prove that it has the effect suppressing HIV1-RT and suppress HIV-1 in cell culture.Study the effect of its 7 kinds of composition Chinese medicines respectively, find that only Radix Scutellariae water extract and composition baicalin (baicalin) thereof have and suppress HIV-1 effect, HIV1-RT is suppressed in vitro in cell free system, HIV-1 cytopathy is suppressed in human T-cell and peripheral blood lymphocytes cultivate, FLuorescent antigen and P24 antigen, in body, oral splenomegaly and the blood leukocytes of suppressing of murine leukemia virus infecting mouse raises.Japan Ono reports that noroxylin (baicalien) suppresses HIV1-RT.
In grind No. I: in grind No. I commodity such as (principal agent has Herba Violae, Radix Trichosanthis composition) and be called: Chinese mugwort
Gram electuary take heat-clearing and toxic substances removing as the rule for the treatment of, by Chinese medicine research institute of China prescription 1992-1993 in African Tanzania to the clinical practice of early metaphase acquired immune deficiency syndrome (AIDS), think to have and necessarily improve symptom, improve the effect of immunity.Laboratory proves that this medicine vitro inhibition hiv reverse transcriptase is active, simian acquired immunodeficiency syndrome poison infected monkey experimental therapy result is shown in body, plasma viral titre can be reduced, and cd4 cell number and CD4/CD8 ratio and T can be improved, bone-marrow-derived lymphocyte numerical value, inducement interferon and generation immunoloregulation function.Once in Africa and China's clinic trial, not yet clinical verification was ratified.
Zhongyan No. 2: Zhongyan No. 2 (Radix Astragali, Radix Ginseng, Radix Angelicae Sinensis, Fructus Lycii and Radix Glycyrrhizae etc.) is China's traditional Chinese medical science
Academy medical team prescription.1992 at African Tanzania treatment AIDS patients.1998-1999 is at African special outpatient clinic to 29 routine AIDS patients treatments, and 2/16 routine HIV virus load declines, and the routine CD4 of CD4 8/29 raises.2001-2002 helps the routine AIDS patients of peace hospitalize 15 in Beijing, 3/15 routine virus load declines, and the routine CD4 of CD4 1/15 raises.Be improved the effect of symptom.Experiment proves that this medicine shows simian acquired immunodeficiency syndrome poison infected monkey experimental therapy in human body, and medication 4-12 week can reduce plasma viral titre, P27 antigen, and can improve cd4 cell number, has activation to infected monkey lymphocyte.
Exhibition hair Herba delphinii grandiflori is be ranunculaceae plant exhibition hair Herba delphinii grandiflori Delphinium kamaonense Huth var.glabrescens (W.T.Wang) W.T.Wang and the dry aerial parts belonging to several plants together.6 ~ August gathers, and dries.Record in " Drug Standard of Ministry of Public Health of the Peoples Republic of China Tibetan medicine (first) ", standard number: WS3-BC-0088-95.Cool in nature, bitter in the mouth.There is heat clearing away, antidiarrheal dysentery, more effect of skin ulcer.For intestinal heat diarrhoea, dysentery; The external application open sore part.The common drug of the minority areas such as illiteracy is hidden for China.But about the basic research of exhibition hair Herba delphinii grandiflori is still very limited, the follow-up promotion and application of this medical material are restricted.Modern study shows, exhibition hair Herba delphinii grandiflori contains alkaloids composition; Exhibition hair Herba delphinii grandiflori pharmacological research has no report.
Domestic patent search result, has no exhibition hair Herba delphinii grandiflori Patents.
Above-mentioned document and patent etc., there is not yet exhibition hair Herba delphinii grandiflori or open up the report of hair Herba delphinii grandiflori extract for the preparation for the treatment of AIDS-treating medicine.
Summary of the invention
A kind of mao Herba delphinii grandiflori extract of opening up is the object of the present invention is to provide to prepare the application in treatment AIDS-treating medicine.
The present invention is achieved through the following technical solutions:
The present invention's exhibition hair used Herba delphinii grandiflori is ranunculaceae plant exhibition hair Herba delphinii grandiflori Delphinium kamaonense Huth var.glabrescens (W.T.Wang) W.T.Wang and the dry aerial parts belonging to several plants together.
The present invention is a kind of opens up the application of mao Herba delphinii grandiflori extract in preparation treatment AIDS-treating medicine, and the preparation method of described exhibition hair Herba delphinii grandiflori extract is:
(1) hair Herba delphinii grandiflori is opened up, with concentration 50%-95% ethanol as solvent, extract at 30 DEG C of-60 DEG C of warm macerating, extraction time is 2-6 time, each extraction time is 2-8 hour, each solvent load is 10-30 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 60%-95%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 2-5 time, each extraction time is 1-6 hour, and each solvent load is 6-20 times of exhibition hair Herba delphinii grandiflori weight, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 30%-80%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B, wherein one or both mix by a certain percentage, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
The preparation method of exhibition hair Herba delphinii grandiflori extract is:
(1) hair Herba delphinii grandiflori is opened up, with concentration 50%-95% ethanol as solvent, extract at 30 DEG C of-60 DEG C of warm macerating, extraction time is 2-6 time, each extraction time is 2-8 hour, each solvent load is 10-30 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 60%-95%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 2-5 time, each extraction time is 1-6 hour, and each solvent load is 6-20 times of exhibition hair Herba delphinii grandiflori weight, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 30%-80%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, exhibition hair Herba delphinii grandiflori extract of the present invention is obtained.
Preferred the present invention opens up a mao preparation method for Herba delphinii grandiflori extract:
(1) hair Herba delphinii grandiflori is opened up, with concentration 70% ethanol as solvent, extract at 50 DEG C of warm macerating, extraction time is 3 times, each extraction time is 4 hours, each solvent load is 20 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.10, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by D101 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting successively of concentration 60%, collect 60% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract A must be opened up;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load is 10 times of exhibition hair Herba delphinii grandiflori weight, and filter, extracting solution is concentrated into relative density d=1.11, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by DM130 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting of concentration 70%, collect 70% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract B must be opened up;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, exhibition hair Herba delphinii grandiflori extract of the present invention is obtained.
The preparation method that exhibition hair Herba delphinii grandiflori of the present invention extracts, is characterized in that: the nonpolar macroporous adsorption resin adopted is AB-8 macroporous adsorbent resin, D101 macroporous adsorbent resin; The polar macroporous adsorption resin adopted is DM130 macroporous adsorbent resin, ADS-3 macroporous adsorbent resin.
The application of exhibition hair Herba delphinii grandiflori extract of the present invention in preparation treatment AIDS-treating medicine.
Exhibition hair Herba delphinii grandiflori extract A of the present invention, the application of exhibition hair Herba delphinii grandiflori extract B in preparation treatment AIDS-treating medicine.
The treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract of the present invention and chemical drugs or Chinese medicine or natural drug form.
The treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract A of the present invention, exhibition hair Herba delphinii grandiflori extract B form with chemical drugs or Chinese medicine or natural drug.
Exhibition hair Herba delphinii grandiflori extract of the present invention, by adding the various adjuvants that pharmaceutics allows, makes the peroral dosage forms such as the tablet on pharmaceutics, granule, capsule.
The present invention's exploratory development first treats acquired immune deficiency syndrome (AIDS) extract with the dry seed of leguminous plant exhibition hair Herba delphinii grandiflori Mucuna birdwoodiana Tutcher for raw material extracts preparation.This experimentation shows, the external infected by influenza of the exhibition each extract of hair Herba delphinii grandiflori, parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), Coxsackie virus B 4 type (C
oxb
4), adenovirus type III ((Ard
3) and rhinoviral cytopathy comparatively virus control group alleviate all to some extent.There is obvious inhibitory action to mouse influenza pneumonia in body, have significant protective effect to influenza to dead mouse, show that each extract of exhibition hair Herba delphinii grandiflori has good antivirus action.Clinical observation result of the test shows, takes 12 routine HIV sufferers of exhibition hair Herba delphinii grandiflori extract for treating, obviously improves symptom, repairs hepatic and renal function, improve, stablize or prolong CD
4decline, suppress virus replication etc. to have obvious curative effect.
Detailed description of the invention
Open up the application that mao Herba delphinii grandiflori extract treats in AIDS-treating medicine in preparation below by specific experiment example and embodiment be described further a kind of, but be not limited to the present invention.
Embodiment 1: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) hair Herba delphinii grandiflori 20kg is opened up, with concentration 70% ethanol as solvent, extract at 50 DEG C of warm macerating, extraction time is 3 times, each extraction time is 4 hours, each solvent load is 20 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.10, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by D101 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting of concentration 60%, collect 60% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract A must be opened up;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load is 10 times of exhibition hair Herba delphinii grandiflori weight, and filter, extracting solution is concentrated into relative density d=1.11, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by ADS-3 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting of concentration 70%, collect 70% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract B must be opened up;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, exhibition hair Herba delphinii grandiflori extract of the present invention is obtained.
Embodiment 2: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) hair Herba delphinii grandiflori 25kg is opened up, with concentration 50% ethanol as solvent, extract at 60 DEG C of warm macerating, extraction time is 6 times, each extraction time is 2 hours, each solvent load is 10 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.12, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by AB-8 nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 60%, collect 60% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract A must be opened up;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 2 times, and each extraction time is 6 hours, and each solvent load is 20 times of exhibition hair Herba delphinii grandiflori weight, and filter, extracting solution is concentrated into relative density d=1.05, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by ADS-3 polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 30%, collect 30% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract B must be opened up;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, exhibition hair Herba delphinii grandiflori extract of the present invention is obtained.
Embodiment 3: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) hair Herba delphinii grandiflori is opened up, with concentration 95% ethanol as solvent, extract at 30 DEG C of warm macerating, extraction time is 2 times, each extraction time is 8 hours, each solvent load is 30 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by D101 nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 95%, collect 95% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract A must be opened up;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 5 times, and each extraction time is 1 hour, and each solvent load is 6 times of exhibition hair Herba delphinii grandiflori weight, and filter, extracting solution is concentrated into relative density d=1.12, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by ADS-3 polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 80%, collect 80% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract B must be opened up;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, exhibition hair Herba delphinii grandiflori extract of the present invention is obtained.
Embodiment 4: the preparation of exhibition hair Herba delphinii grandiflori extract sheet
Example 1 opens up hair Herba delphinii grandiflori extract 270g, adds starch 70g, mixing, granulates, dry, sieves, adds microcrystalline Cellulose 25g, magnesium stearate 3g, and mixing, is pressed into 1000, must opens up hair Herba delphinii grandiflori extract sheet.
Embodiment 5: the preparation of exhibition hair Herba delphinii grandiflori extract particles
Example 2 opens up hair Herba delphinii grandiflori extract 150g, adds dextrin 95g, mixing, granulates, and dry, granulate, must open up hair Herba delphinii grandiflori extract particles.
Embodiment 6: the preparation of exhibition hair Herba delphinii grandiflori extract capsule
Example 3 opens up hair Herba delphinii grandiflori extract 240g, adds starch 85g, mixing, granulates, and dry, granulate, must open up hair Herba delphinii grandiflori extract capsule by encapsulated 1000.
Experimental example l: the antivirus action of each extract of exhibition hair Herba delphinii grandiflori
Test material: open up hair Herba delphinii grandiflori extract, exhibition hair Herba delphinii grandiflori extract A, (prepare by the embodiment of the present invention 1 method, lot number is respectively exhibition hair Herba delphinii grandiflori extract B: 20110708,20110709,20110710); Virazole (ribavirin) is produced by Hubei Province's institute of Pharmaceutical Industry, lot number: 20110503; SHUANGHUANGLIAN JIAONANG is produced by Jinghai Pharmaceutical Co., Ltd., Beijing, lot number: 20110701; Influenza virus A 3 type, the sick 4 type (C of coxsackie B race
oxb
4), parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), adenovirus type III (Ard
3), rhinovirus 14 type and influenza virus A-prime Mus lung adapted strain FM1, respectively purchased from Virology Inst., Chinese Academy of Preventive Medical Science and institute of pediatrics; People's laryngeal carcinoma passage cell HEP-2 strain, purchased from Ministry of Public Health pharmaceutical biological product calibrating institute; Containing 10% calf serum, 0.29mg paddy ammonia phthalein amine/m1,100 μ l are blue or green, the Eagle'MEM of Streptomycin; Cell maintenance medium, except contained calf serum is except 2%, all same culture fluid of other content.Kunming mouse, is provided by Shandong Province's Experimental Animal Center.
Experimental technique
1. antiviral effect in vitro: the toxicity test to Hep-2 cultured cell: medicinal liquid Eagle's is cultivated and makes 1:20-1:1280 doubling dilution, be added to and grow up in the HEP-2 Tissue Culture Plate of monolayer, 100 μ l/ holes, each dilution factor medicinal liquid does 3 multiple holes, establishes normal cell controls simultaneously.Culture plate is put 37 DEG C, 5% C0
2cultivate 4 days in incubator, observation of cell growing state under every day inverted microscope, determines that cell does not occur that the minimum of obvious regression releases rare multiple, postpones and accomplish minimum effective drug concentration (maximum dilution multiple) during experiment.50% toxic concentration (TC is calculated by Reed-Muench method
50) and maximal non-toxic concentration (TC
0), the results are shown in Table 1.
The TC of table 1 pair cultured cell
0tC
50(mg/ml).
2. interior resisting virus effect: the inhibitory action to mouse influenza virus pneumonia: get mice 70,7 groups are divided at random by body weight, be respectively intact animal's matched group, virus-infected controls group, trial drug 3 groups (exhibition hair Herba delphinii grandiflori extract, exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B), virazole group, SHUANGHUANGLIAN JIAONANG group.Except Normal group, mice is used ether light anesthesia, infect with 15 LD50 influenza virus drop noses, every 0.05ml.Gastric infusion from infecting the previous day, every day 3 times, each 0.5ml, continuous 5 days, matched group is distilled water gavage under equal conditions.Dissect after within 6th day, taking Mouse Weight, perusal pulmonary lesion, the degree of record pulmonary liver sample consolidation, wins full lung and weighs, calculate Lung Exponent value one by one, and obtain lung index.Result: the mice pneumonia that exhibition hair Herba delphinii grandiflori each extract infected by influenza causes all has obvious inhibitory action, the results are shown in Table 2.
The inhibitory action of table 2 pair mouse influenza virus pneumonia
Note: compare with Normal group:
##p<0.01; Compare with virus control group: * * P<0.01, * P<0.05.
3. the protective effect of infected by influenza induced mice death: get mice 120, be divided into 6 groups at random by body weight.Be respectively trial drug three dosage groups, virazole group, SHUANGHUANLIAN group and virus-infected controls group.Each group of mice, with after ether light anesthesia, infects with 2 LD50 influenza virus drop noses, every 0.05ml.Gastric infusion from infecting the previous day, every day 3 times, each 0.5ml, continuous 7 days.The accumulative death toll infecting rear mice, calculates mortality rate, protective rate and increase in life span, the results are shown in Table 3,4.
Table 3 infected by influenza causes the protective effect of dead mouse
Note: compare with infection matched group:
*p<0.0l,
*p<0.05.
Table 4 infected by influenza causes the protective effect of dead mouse
Note: compare with infection matched group:
*p<0.0l,
*p<0.05.
Table 3; table 4 result show: mouse infection virus latter 14 days in; the death toll of exhibition hair Herba delphinii grandiflori each extract group mice comparatively infects matched group and obviously reduces; mice Average Survival natural law comparatively infects matched group and obviously extends, and shows that trial drug infected by influenza infection when this dosage causes dead mouse and has certain protective role.
The external infected by influenza of the exhibition each extract of hair Herba delphinii grandiflori, parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), Coxsackie virus B 4 type (C is found in experimentation
oxb
4), adenovirus type III ((Ard
3) and rhinoviral cytopathy comparatively virus control group alleviate all to some extent.There is obvious inhibitory action to mouse influenza pneumonia in body, have significant protective effect to influenza to dead mouse, show that each extract of exhibition hair Herba delphinii grandiflori has good antivirus action, therefore have the basis developed preferably.
Experimental example 2: the clinical observation on the therapeutic effect of exhibition hair Herba delphinii grandiflori extract for treating acquired immune deficiency syndrome (AIDS)
Physical data: 12 routine cases are all HIV sufferers through hospital diagnosis, accept clinical research voluntarily; Can adhere to that accepting assessment detects and treatment; Age 21-63 year; Man 8 example, female 3 example; 32 years old mean age.All case never received antiviral treatments.
Diagnostic criteria: all cases all meet HIV/AIDS diagnostic criteria.
Therapeutic Method: all oral the present invention of all cases opens up a mao Herba delphinii grandiflori extract, a 1g, 3 times on the one 30 days is a course for the treatment of.
Clinical efficacy evaluation criteria: " the Treating AIDS with Traditional Chinese Medicine pilot project clinical technology scheme " formulated according to State Administration of Traditional Chinese Medicine, the standard of curative effect evaluation is as follows: effectively: Clinical symptom and sign improves obviously, and total mark declines>=1/3; CD
4rising>=30% or 50 μ l; Virus load reduces >0.5log/ml; Stable: Clinical symptom and sign makes moderate progress, total mark decline <1/3; CD
4raise or decline <30% or 50 μ l; Virus load rises or decline <0.5log/ml.Invalid: Clinical symptom and sign is without improvement or increase the weight of, and total mark does not decline or increases; CD
4decline>=30% or 50 μ l; Viral load levels continues to rise, copy number rising >0.5log/ml.
Result is tired out in clinical sight: symptom and sign change before and after treatment: effective 8 examples, stable: 4 examples, invalid: 0 example.
CD before and after treatment
4cellular change: effective 7 examples is stable: 4 examples, invalid: 1 example.
Virus load change before and after treatment: effective 7 examples, stable: 4 examples, invalid: 1 example.
Clinical observation result shows: the 12 routine HIV sufferers taking exhibition hair Herba delphinii grandiflori extract for treating, obviously improves symptom, repairs hepatic and renal function, improve, stablize or prolong CD
4decline, suppress virus replication etc. to have obvious curative effect.
Claims (12)
1. open up the application of mao Herba delphinii grandiflori extract in preparation treatment AIDS-treating medicine, the preparation method of described exhibition hair Herba delphinii grandiflori extract is:
(1) hair Herba delphinii grandiflori is opened up, with concentration 50%-95% ethanol as solvent, extract at 30 DEG C of-60 DEG C of warm macerating, extraction time is 2-6 time, each extraction time is 2-8 hour, each solvent load is 10-30 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density 1.05-1.12, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 60%-95%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 2-5 time, each extraction time is 1-6 hour, and each solvent load is 6-20 times of exhibition hair Herba delphinii grandiflori weight, filters, extracting solution is concentrated into relative density 1.05-1.12, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 30%-80%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, hair Herba delphinii grandiflori extract must be opened up.
2. open up the preparation method of hair Herba delphinii grandiflori extract:
(1) hair Herba delphinii grandiflori is opened up, with concentration 50%-95% ethanol as solvent, extract at 30 DEG C of-60 DEG C of warm macerating, extraction time is 2-6 time, each extraction time is 2-8 hour, each solvent load is 10-30 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density 1.05-1.12, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by nonpolar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 60%-95%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 2-5 time, each extraction time is 1-6 hour, and each solvent load is 6-20 times of exhibition hair Herba delphinii grandiflori weight, filters, extracting solution is concentrated into relative density 1.05-1.12, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by polar macroporous adsorption resin, first wash with water, then use the alcoholic solution eluting of concentration 30%-80%, collect different concentration ethanol eluent, concentrate drying, must open up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, hair Herba delphinii grandiflori extract must be opened up.
3. open up the preparation method of hair Herba delphinii grandiflori extract according to claim 2:
(1) hair Herba delphinii grandiflori is opened up, with concentration 70% ethanol as solvent, extract at 50 DEG C of warm macerating, extraction time is 3 times, each extraction time is 4 hours, each solvent load is 20 times of exhibition hair Herba delphinii grandiflori weight, filters, obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density 1.10, filter, obtain medicinal liquid A;
(2) by the medicinal liquid A that step (1) obtains, by D101 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting successively of concentration 60%, collect 60% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract A must be opened up;
(3) step (1) being obtained medicinal residues A water is solvent, reflux, extract, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load is 10 times of exhibition hair Herba delphinii grandiflori weight, and filter, extracting solution is concentrated into relative density 1.11, filters, obtains medical liquid B;
(4) by the medical liquid B that step (3) obtains, by DM130 macroporous adsorbent resin, first wash with water, then use the alcoholic solution eluting of concentration 70%, collect 70% concentration ethanol eluent, concentrate drying, hair Herba delphinii grandiflori extract B must be opened up;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, the mixing of exhibition hair Herba delphinii grandiflori extract B, hair Herba delphinii grandiflori extract must be opened up.
4. application according to claim 1, is characterized in that adopted nonpolar macroporous adsorption resin is AB-8 macroporous adsorbent resin, D101 macroporous adsorbent resin; The polar macroporous adsorption resin adopted is DM130 macroporous adsorbent resin, ADS-3 macroporous adsorbent resin.
5. the preparation method of exhibition hair Herba delphinii grandiflori extract according to claim 2, is characterized in that: the nonpolar macroporous adsorption resin adopted is AB-8 macroporous adsorbent resin, D101 macroporous adsorbent resin; The polar macroporous adsorption resin adopted is DM130 macroporous adsorbent resin, ADS-3 macroporous adsorbent resin.
6. the treatment AIDS-treating medicine that forms of exhibition hair Herba delphinii grandiflori extract according to claim 1 and chemical drugs or Chinese medicine or natural drug.
7. the application of exhibition hair Herba delphinii grandiflori extract A according to claim 1 in preparation treatment AIDS-treating medicine.
8. the application of exhibition hair Herba delphinii grandiflori extract B according to claim 1 in preparation treatment AIDS-treating medicine.
9. the treatment AIDS-treating medicine that forms of exhibition hair Herba delphinii grandiflori extract A according to claim 1 and chemical drugs or Chinese medicine or natural drug.
10. the treatment AIDS-treating medicine that forms of exhibition hair Herba delphinii grandiflori extract B according to claim 1 and chemical drugs or Chinese medicine or natural drug.
11. application according to claim 1, is characterized in that the various adjuvants that described exhibition hair Herba delphinii grandiflori extract allows by adding pharmaceutics, making tablet, granule, capsule.
12. according to claim 2 or preparation method according to claim 3, it is characterized in that the various adjuvants that described exhibition hair Herba delphinii grandiflori extract allows by adding pharmaceutics, making tablet, granule, capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525344.XA CN103585291B (en) | 2013-10-31 | 2013-10-31 | Application of herba delphinii extract in preparation of drugs treating AIDS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525344.XA CN103585291B (en) | 2013-10-31 | 2013-10-31 | Application of herba delphinii extract in preparation of drugs treating AIDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103585291A CN103585291A (en) | 2014-02-19 |
| CN103585291B true CN103585291B (en) | 2015-06-03 |
Family
ID=50075745
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310525344.XA Expired - Fee Related CN103585291B (en) | 2013-10-31 | 2013-10-31 | Application of herba delphinii extract in preparation of drugs treating AIDS |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103585291B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110604795A (en) * | 2019-09-27 | 2019-12-24 | 山东佳硒雅生物有限公司 | Gynecological inflammation gel and preparation method thereof |
-
2013
- 2013-10-31 CN CN201310525344.XA patent/CN103585291B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN103585291A (en) | 2014-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20030054047A1 (en) | Pharmaceutical composition for the treatment of viral infection | |
| CN102552512B (en) | Traditional Chinese medicine used for treating hepatitis B | |
| CN103585291B (en) | Application of herba delphinii extract in preparation of drugs treating AIDS | |
| CN101695562B (en) | Chinese medicinal composition for treating viral hepatitis and preparation method thereof | |
| CN103585259B (en) | The application of a kind of Mucuna birdwoodiana Tutcher extract in preparation treatment AIDS-treating medicine | |
| CN101044857A (en) | Application of compounding preparation in medicine for treating human Aids hepatitis and skin diseases | |
| CN103585222B (en) | The application of a kind of Ligularia purdomii extract in preparation treatment AIDS-treating medicine | |
| CN103585212B (en) | The application of Dorema ammoniacum resin extract in preparation treatment AIDS-treating medicine | |
| CN102805810B (en) | Chinese medicinal preparation for treating acquired immune deficiency syndrome (AIDS) and preparation method thereof | |
| CN102198192A (en) | Traditional Chinese medicine composition for treating HINI and application thereof | |
| CN103585239B (en) | A kind of preparation method of Boraginaceae extract and application thereof | |
| CN103585188B (en) | The application of wall tapestry extract in preparation treatment AIDS-treating medicine | |
| CN103585219B (en) | The application of a kind of Altay Heteropappus hispidus (Thunb.) Less.-Aster hispidus Thunb． extract in preparation treatment AIDS-treating medicine | |
| CN103585197B (en) | The application of mesh Herba Lepisori Thunbergiani extract in preparation treatment AIDS-treating medicine | |
| CN103585236B (en) | The application of Radix Berberidis Amurensis berry extract in preparation treatment AIDS-treating medicine | |
| CN103585223B (en) | The application of Herba Elephantopi Mollis extract in preparation treatment AIDS-treating medicine | |
| CN104510742A (en) | Pharmaceutical composition for treating AIDS | |
| CN104510740A (en) | Pharmaceutical composition for treating AIDS | |
| CN1315480C (en) | Herpes virus treating medicine composition and its production process | |
| CN102614467A (en) | Traditional Chinese medical composition for treatment of acquired immunodeficiency syndrome and preparation method and application thereof | |
| CN1981812B (en) | Chinese-medicinal preparation for treating AIDS and its production | |
| CN104510741A (en) | Pharmaceutical composition for treating AIDS | |
| CN104208250B (en) | A kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) | |
| CN104510739A (en) | Pharmaceutical composition for treating AIDS | |
| CN104510734A (en) | Pharmaceutical composition for treating AIDS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: TAISHAN HOSPITAL Free format text: FORMER OWNER: JINAN XINGYI MEDICAL TECHNOLOGY CO., LTD. Effective date: 20150512 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Yanlin Inventor after: Wang Yanhui Inventor after: Zhang Weitao Inventor after: Yin Ling Inventor after: Chen Wenwen Inventor before: Kong Qianqian |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 250101 JINAN, SHANDONG PROVINCE TO: 271016 TAIAN, SHANDONG PROVINCE Free format text: CORRECT: INVENTOR; FROM: KONG QIANQIAN TO: LIU YANLIN WANG YANHUI ZHANG WEITAO YIN LING CHEN WENWEN |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20150512 Address after: 271016 the Great Wall Road, Shandong, Tai'an, No. 619 Applicant after: Taishan Hospital Address before: 250101 No. 51 Industrial South Road, Ji'nan hi tech Zone, Shandong, Ji'nan Applicant before: Jinan Xingyi Medical Technology Co.,Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150603 Termination date: 20181031 |