CN1935762A - Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus - Google Patents
Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus Download PDFInfo
- Publication number
- CN1935762A CN1935762A CN 200610053827 CN200610053827A CN1935762A CN 1935762 A CN1935762 A CN 1935762A CN 200610053827 CN200610053827 CN 200610053827 CN 200610053827 A CN200610053827 A CN 200610053827A CN 1935762 A CN1935762 A CN 1935762A
- Authority
- CN
- China
- Prior art keywords
- compound
- mapping
- hepatitis
- formula
- eucalyptus
- 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
- 230000002401 inhibitory effect Effects 0.000 title abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title abstract description 3
- 229930004725 sesquiterpene Natural products 0.000 title description 30
- 150000004354 sesquiterpene derivatives Chemical class 0.000 title description 27
- 241000700605 Viruses Species 0.000 title description 10
- 208000006454 hepatitis Diseases 0.000 title description 4
- 231100000283 hepatitis Toxicity 0.000 title description 3
- 230000000694 effects Effects 0.000 claims abstract description 23
- 230000005764 inhibitory process Effects 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 62
- 229930182470 glycoside Natural products 0.000 claims description 28
- 208000002672 hepatitis B Diseases 0.000 claims description 27
- 241001269712 Laggera Species 0.000 claims description 25
- 238000013507 mapping Methods 0.000 claims description 23
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 20
- 241000700721 Hepatitis B virus Species 0.000 claims description 19
- 239000000427 antigen Substances 0.000 claims description 17
- 102000036639 antigens Human genes 0.000 claims description 17
- 108091007433 antigens Proteins 0.000 claims description 17
- 150000002338 glycosides Chemical class 0.000 claims description 15
- 244000274638 Laggera alata Species 0.000 claims description 14
- 241000196324 Embryophyta Species 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 210000001541 thymus gland Anatomy 0.000 claims description 8
- 244000166124 Eucalyptus globulus Species 0.000 claims description 7
- LKKDASYGWYYFIK-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-1,4a-dimethyl-decahydronaphthalen-1-ol Chemical compound C1CCC(C)(O)C2CC(C(C)(O)C)CCC21C LKKDASYGWYYFIK-UHFFFAOYSA-N 0.000 claims description 6
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 241001529246 Platymiscium Species 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- DJOWTWWHMWQATC-KYHIUUMWSA-N Karpoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1(O)C(C)(C)CC(O)CC1(C)O)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C DJOWTWWHMWQATC-KYHIUUMWSA-N 0.000 claims description 3
- 239000002131 composite material Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- ODDNJYHUVXKJBI-UHFFFAOYSA-N pterodontriol B Natural products OC1CCC(C)(O)C2CC(C(C)(O)C)CCC21C ODDNJYHUVXKJBI-UHFFFAOYSA-N 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 claims description 3
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 claims description 2
- 244000192528 Chrysanthemum parthenium Species 0.000 claims description 2
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 235000008384 feverfew Nutrition 0.000 claims description 2
- 239000010408 film Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002402 hexoses Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000865 liniment Substances 0.000 claims description 2
- 229940040145 liniment Drugs 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 16
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 abstract description 8
- 229960001627 lamivudine Drugs 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 230000010076 replication Effects 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000009385 viral infection Effects 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 229930182478 glucoside Natural products 0.000 abstract 1
- 150000008131 glucosides Chemical class 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- VGAJNILINWUWOP-UHFFFAOYSA-N Eudesmane Natural products COC(=O)C(=C)C1C(O)C2C(=O)CCC(O)C2(C)CC1OC(=O)C(=C)CO VGAJNILINWUWOP-UHFFFAOYSA-N 0.000 description 28
- DYEQPYSFRWUNNV-APIJFGDWSA-N eudesmane Chemical compound C1CC[C@@H](C)[C@@H]2C[C@H](C(C)C)CC[C@]21C DYEQPYSFRWUNNV-APIJFGDWSA-N 0.000 description 27
- -1 sesquiterpene alcohol derivatives Chemical class 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000000452 restraining effect Effects 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 10
- 230000000840 anti-viral effect Effects 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 230000004543 DNA replication Effects 0.000 description 2
- 241000725643 Respiratory syncytial virus Species 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000223019 Caragana korshinskii Species 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241001269715 Laggera pterodonta Species 0.000 description 1
- 241000218195 Lauraceae Species 0.000 description 1
- 241001620208 Litsea verticillata Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- QRVJFHKYVKNIIK-MYYUVRNCSA-N Pterocarptriol Natural products OC(C)(C)[C@H]1C[C@H]2[C@@](O)(C)C[C@H](O)C[C@]2(C)CC1 QRVJFHKYVKNIIK-MYYUVRNCSA-N 0.000 description 1
- 241000545405 Tripterygium Species 0.000 description 1
- 241001197778 Tripterygium hypoglaucum Species 0.000 description 1
- 241000830536 Tripterygium wilfordii Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000003097 anti-respiratory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- CSJIHBJWGQPLPI-LUBZDXBGSA-N chembl1169612 Chemical compound C([C@]1(C)O2)OC(=O)C3=CN=CC=C3[C@@H](C)[C@@H](O)C(=O)O[C@H]([C@]3(C)O)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@]4([C@@H]5OC(C)=O)[C@@]23[C@H](OC(C)=O)[C@H]1[C@H]5OC(=O)[C@@H](C)CCC(=O)[C@@H](CC(=O)OC)C(=O)OC4 CSJIHBJWGQPLPI-LUBZDXBGSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000000174 eudesmanes Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229930194935 pterodontriol Natural products 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Natural products 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 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 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
- GSBZVVMZYQMZBG-UHFFFAOYSA-N triptonine B Natural products O1C2(C)COC(=O)C3=CN=CC=C3C(C)C(C)(O)C(=O)OC(C3(C)O)C(OC(C)=O)C(OC(C)=O)C4(C5OC(C)=O)C13C(OC(C)=O)C2C5OC(=O)C(C)CCC(=O)C(CC(=O)OC)C(=O)OC4 GSBZVVMZYQMZBG-UHFFFAOYSA-N 0.000 description 1
- CKGNGZNSTIOFOY-XQLPTFJDSA-N verticillatol Chemical compound O[C@H]1CCC(=C)[C@@]2(O)C[C@@H](C(C)C)CC[C@@]21C CKGNGZNSTIOFOY-XQLPTFJDSA-N 0.000 description 1
- CKGNGZNSTIOFOY-UHFFFAOYSA-N verticillatol Natural products OC1CCC(=C)C2(O)CC(C(C)C)CCC21C CKGNGZNSTIOFOY-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an enantiomorphic amine alkyl sesquiterpene alcohol and glucoside and the medicated salt or solvent thereof, as well as the effect and activity of the composed medicine combination, mainly relating to the medical use in reducing HBV-DNA replication activity. And it has considerably strong inhibiting effect on HBsAG screted by HepG2.2.15 and HBV-DNA replication as compared with positive contrast Lamivudine; and it has obvious inhibition activity to HBV-DNA replication at large dosage (100 mug/mL) and medium dosage(20 mug/mL) as contrasted with Lamivudine, and can be expected to apply to preparing medicines for curing HB virus infection disease.
Description
Technical field
The drug activity of the pharmaceutical composition that the present invention relates to a pure and mild glycosides of class mapping eudesmane type sesquiterpene and pharmacologically acceptable salt thereof or solvate and form thus relates generally to it at the medicinal use that reduces hepatitis B surface antigen(HBsAg) and suppress hepatitis B virus thymus nucleic acid (HBV-DNA) replication activity.
Technical background
Hepatitis B (abbreviation hepatitis B) is the transmissible disease that is caused by hepatitis B virus (HBV), by blood and body fluid communication, has chronic carrier state.This disease is widely current in China, crowd infection rate's height, and infection rate reaches more than 35% in certain areas.According to pertinent data, the patient of hepatitis tests positive reaction has reached 1.89 hundred million, and the number (carrier) nearly 400,000,000 of should not going to a doctor.It is one of the most serious transmissible disease of current harm people ' s health.Hepatitis B clinical manifestation variation easily develops into chronic hepatitis and liver cirrhosis, and a few patients can change primary hepatocarcinoma into.Now the medicine of hepatitis B mainly contains nucleoside medicine, protects the liver class medicine and immunological reagent etc., but equal progress of disease controlling fully.At present the most frequently used in the nucleoside medicine also is lamivudine the most effectively, but its life-time service can cause resistance, easily knock-on after the drug withdrawal, and this has had a strong impact on the curative effect of this medicine.
The present antiviral of the using inhibitor of virus replication just in fact, directly kill virus and break virus body, otherwise will damage host cell.These antiviral also exist toxic side effect greatly, easily to cause after virogene sudden change, the drug withdrawal shortcomings such as easily knock-on, so the development of new antiviral drug is the task of top priority in current medicament research and development field.
Eudesmane type sesquiterpene is the terpenoid that 15 carbon constitute skeletons, and this compounds generally has multiple biological activity, and report focuses mostly in antitumor, antibiotic, antimalarial and antimycotic direction.External this eudesmane type sesquiterpene alcohol derivatives of discovery in the recent period has multiple antiviral activity.As (Journal of Antimicrobial Chemotherapy such as Hayashi in 1996,1996,37 (4), separate when 759-768) Tripterygium platymiscium Tripterygium wilfordii Hook fil.var.regelii Makino being studied and obtained one herpes simplex types 1 virus (Herpes simplex virustype 1, HSV-1) (treatment index TI) surpasses 10 compound TriptofordinC-2 (compound 1) to the selective therapy index.
(Tennen Yuki Kagobutsu Toronkai Koen Yoshishu such as Duan in 1999,1999,41st, 535-540) ethyl acetate of the methanol extract of the root position of plant Tripterygium hypoglaucum (Levi.) Hutch that Tripterygium is belonged to has partly been carried out system's separation, obtain compound 2, and find that it has the activity of certain anti AIDS virus (HIV), can promote the generation of cytokine simultaneously.At continuation further investigation (Duan etc. to this plant, Journal ofNatural Products, 2000,63 (3), the new eudesmane type sesquiterpene alcaloid-derivatives Triptonine B (compound 3) that is separated to 357-361) has embodied the activity of potential anti HIV-1 virus, its half virtual value (EC50) is less than 0.1 μ g/ml, and its external treatment index is greater than 1000, so there is very much exploitation to be worth.
(Phytochemistry such as Hoang Vu Dinh in 2002,2002,59 (3), 325-329) separate from Litseaverticillata Hance (Lauraceae) and obtain new eudesmane type sesquiterpene verticillatol (compound 4), it has anti-activity (its 503nhibiting concentration IC that likes magnetic virus to use the test shows of being carried out as model by the osteosarcoma of HIV virus infection (human osteosarcoma) HOG.R5 cell
50Value is 34.5 μ g/ml), when 20 μ g/ml, detect toxicity simultaneously less than its pair cell, can be used as the lead compound of AIDS resisting.
(Journal of Natural Products such as Sun in 2004,2004,67 (12), 1975-1979) reported new eudesmane type sesquiterpene 4 (15)-eucalyptus alkane-1 β that are separated to from Caragana intermedia, the minimum inhibitory concentration that 7 salmefamols (5) are gone into the HIV-IIIB virus of MT-2 cell to infection is 10 μ g/ml, and other three compounds (6,7,8) then shown restraining effect to rice blast virus, minimum inhibitory concentration is respectively 12,16 and 20 μ g/ml.
By above-mentioned result of study as seen, this type of eudesmane type sesquiterpene alcohol has than obvious effects suppressing virus, yet the inventor finds the eudesmane type sesquiterpene compound of having reported so far with antiviral activity and focuses mostly on eucalyptus alkanols compound, and the still rare investigator of mapping eudesmane type sesquiterpene alcohol compound sets foot in.In addition, nobody carries out antiviral activity research and report to the glycosides compound of eudesmane type sesquiterpene especially.The inventor thereby further forefathers are not added the pure and mild glycoside derivative of the mapping eudesmane type sesquiterpene of studying and carry out antiviral activity test.
During the inventor worked in the past systematic study once the chemical ingredients and the pharmacological action of Yunnan treatment influenza among the people and parotitic herbal medicine composite family Laggera alata (Roxb.) Sch.-Bip. platymiscium Wingedtooth Laggera Herb (being tooth wing Laggera alata (Roxb.) Sch.-Bip. Laggera pterodonta (DC.) Benth) and Laggera alata (Roxb.) Sch.-Bip. (Laggera alata (D.Don) Sch.-Bip.ex Oliv), [girth is new, Zhao Yu etc. to find wherein to contain a large amount of pure and mild glycosides compounds of mapping eudesmane type sesquiterpene, CHINA JOURNAL OF CHINESE MATERIA MEDICA, (summary) 2006,31 (14), 1133-1140, and the pertinent literature quoted of this article; Li Shunlin etc., Yunnan plant research, 1993,15 (3), 303; Li Shunlin etc., Yunnan plant research, 1994,16 (3), 313; Zhao Yu (Yu Zhao) etc., Chinese Chemical Letters, 1996,7 (12), 1093; Zhao Yu (Yu Zhao) etc., Phytochemistry, 1997,44 (3), 459; Zhao Yu (Yu Zhao) etc., J.Nat.Prod.1997,60 (6), 545; Zheng Qunxiong, Zhao Yu etc., journal of Zhejiang university (medicine) 2002,31 (6), 406].Even more noteworthy: Hong Kong researchist finds that tooth wing Laggera alata (Roxb.) Sch.-Bip. aqueous extract has anti-I type hsv (HSV-1) effect, half-inhibition concentration (IC in the recent period
50) be 250 μ g/mL, and half cell toxicant concentration (CC
50) be 750 μ g/mL.The IC of while anti respiratory syncytial virus (RSV)
50Be 15.6 μ g/mL, CC
50Be 500 μ g/mL[Li YL, Ooi LSM, Wang H, et al.Antiviral activities of medicinalherbs traditionally used in southern mainland China.Phytother Res, 2004,18 (9): 718].The inventor has done further research on the basis of existing technology, being primarily aimed at the anti-HBV activity of this platymiscium chemical monomer composition screens, discovery belongs to the pure and mild glycosides compound of such mapping eudesmane type sesquiterpene that extracts the medicinal plant from Laggera alata (Roxb.) Sch.-Bip. and has the effect that significant hepatitis B virus resisting reduces hepatitis B surface antigen simultaneously, and consult through document, up to the present, still not about the pure and mild glycoside compound treatment of such mapping eudesmane type sesquiterpene hepatitis B virus infection disease and the report for preparing anti-hepatic-B virus medicine.Finish the present invention in view of the above.
Summary of the invention
The pharmaceutical composition that the purpose of this invention is to provide the pure and mild glycosides of mapping eudesmane type sesquiterpene of the class high-efficiency low-toxicity shown in the formula (1) and pharmacologically acceptable salt thereof or solvate and formed thus, specifically pure and mild glycosides of such mapping eudesmane type sesquiterpene and pharmacologically acceptable salt thereof or solvate are reducing hepatitis B surface antigen(HBsAg) and are suppressing the active medicinal use of hepatitis B viruses (HBV) dna replication dna.
Wherein, R
1, R
2, R
3, R
4, R
5Can be the same or different, can be hydrogen, hydroxyl, contain alkoxyl group, the halogen of 1～8 carbon, also can be replacement or unsubstituted five-carbon sugar or the hexose that links with any configuration and eucalyptus alkane skeleton.Preferably separation and purification from plant of the pure and mild glycosides of mapping eudesmane type sesquiterpene shown in the Chinese style of the present invention (1) more preferably obtains from feverfew, most preferably obtains from composite family Laggera alata (Roxb.) Sch.-Bip. platymiscium Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip..Most preferred formula (1) compound is among the present invention:
Compound 1-a: pterodondiol (pterodondiol, 4 β, 11-dihydroxyl-mapping-eucalyptus alkane);
Compound 1-b: Wingedtooth Laggera Herb triol first (pterodontriolA, 2 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-c: Pterodontriol B (pterodontriolB, 1 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-d: Wingedtooth Laggera Herb triol third (pterodontriolC, 4 β, 8 α, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-e: Wingedtooth Laggera Herb tetrol (pterodontetraol, 1 α, 2 β, 4 β, 11-tetrahydroxy-mapping-eucalyptus alkane);
Compound 1-f:4 β, 9 α, 11-trihydroxy--mapping-eucalyptus alkane (4 β, 9 α, 11-triol-enantio-eudesmane);
Compound 1-g: Wingedtooth Laggera Herb glycosides C (pterodontoside C, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-11-ol);
Compound 1-h: Wingedtooth Laggera Herb glycosides D (pterodontoside D, 11-(β-D-glucopyranosyloxy)-the enantio-eudesma-4 beta-ol);
Compound 1-i: Wingedtooth Laggera Herb glycosides E (pterodontoside E, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-1 α, 11-diol);
Compound 1-j: Pterodontoside F (pterodontoside F, 1 α-(β-D-glucopyranosyloxy)-enantio-eudesma-4 β, 11-diol);
Another purpose of the present invention has provided the purposes that formula (1) compound is used to prevent and treat hepatitis B, reduces hepatitis B surface antigen;
Another object of the present invention has provided a kind of pharmaceutical composition of preventing and treating hepatitis B, reduction hepatitis B surface antigen that contains formula (1) compound, it contains the formula as activeconstituents (1) compound for the treatment of significant quantity, perhaps its pharmacologically acceptable salt or solvate and pharmaceutically acceptable auxiliaries.It can be that tablet, capsule, injection squeeze, aerosol, suppository, film, pill, paster agent, subcutaneous planting bury agent, externally-applied liniment, oral liquid or ointment, can also adopt the known controlled release of modern pharmaceutical circle or slow release formulation or nanometer formulation.
Embodiment
The preparation method of the pure and mild glycosides of mapping eudesmane type sesquiterpene shown in this formula (1), can publish an article referring to investigators such as the inventor [Li Shunlin etc., Yunnan plant research, 1993,15 (3), 303; Li Shunlin etc., Yunnan plant research, 1994,16 (3), 313; Zhao Yu (Yu Zhao) etc., Chinese Chemical Letters, 1996,7 (12), 1093; Zhao Yu (Yu Zhao) etc., Phytochemistry, 1997,44 (3), 459; Zhao Yu (Yu Zhao) etc., J.Nat.Prod.1997,60 (6), 545; Zheng Qunxiong, Zhao Yu etc., journal of Zhejiang university (medicine) 2002,31 (6), 406].Prepare the pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the formula (1) according to the method for describing in the document, its spectroscopic data of each compound that purifying obtains conforms to corresponding reported values in above-mentioned the offering.Below list the part spectroscopic data.Compound 1-a: pterodondiol (pterodondiol, 4 β, 11-dihydroxyl-mapping-eucalyptus alkane); No color lump crystalline substance (acetone), 105～106 ℃ of fusing points; [α]
25 D29.2 (CHCl
3, c2.1); Mass spectrum EIMS:240[M]
+(1), 222,204,164,108,81,41.
Compound 1-b: Wingedtooth Laggera Herb triol first (pterodontriol A, 2 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane); Colourless needle (acetone), 187～188 ℃ of fusing points; Mass spectrum EIMS:256 [M]
+(2), 238,220,205,180,147,106,93,55.
Compound 1-c: Pterodontriol B (pterodontriolB, 1 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane); Colourless needle (acetone), 182～183 ℃ of fusing points; Mass spectrum EIMS:256 [M]
+(1), 238,220,205,187,165,136,98,67,59.
Compound 1-d: Wingedtooth Laggera Herb triol third (pterodontriol C, 4 β, 8 α, 11-trihydroxy--mapping-eucalyptus alkane); Colourless column crystal (methyl alcohol), 193～194 ℃ of fusing points; Mass spectrum EIMS:256 [M]
+(0.5), 238,220,205,187,180,177,162,147,109,95,59.
Compound 1-e: Wingedtooth Laggera Herb tetrol (pterodontetraol, 1 α, 2 β, 4 β, 11-tetrahydroxy-mapping-eucalyptus alkane); Colourless powder (acetone), fusing point＞228 ℃ (decomposition); Mass spectrum EIMS:254[M-H
2O]
+(1), 236,218,200,165,105,59.
Compound 1-f:4 β, 9 α, 11-trihydroxy--mapping-eucalyptus alkane (4 β, 9 α, 11-triol-enantio-eudesmane); Colourless needle (acetone), 183～184 ℃ of fusing points; Mass spectrum EIMS:256[M]
+(0.5), 238,220,187,162,103,67.
Compound 1-g: Wingedtooth Laggera Herb glycosides C[pterodontoside C, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-11-ol]; Colourless powder (methyl alcohol), 187～188 ℃ of fusing points; Mass spectrum EIMS:240[M-glucosyl group]
+(2), 222,204,189,149,109,81,69.
Compound 1-h: Wingedtooth Laggera Herb glycosides D[pterodontoside D, 11-(β-D-glucopyranosyloxy)-the enantio-eudesma-4 beta-ol]; Colourless powder (methyl alcohol), 193～194 ℃ of fusing points; Mass spectrum EIMS:240[M-glucosyl group]
+(4), 222,204,189,137,81,55.
Compound 1-i: Wingedtooth Laggera Herb glycosides E[pterodontoside E, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-1 α, 11-diol]; Colourless powder (methyl alcohol), 203～205 ℃ of fusing points; Mass spectrum EIMS:256[M-glucosyl group]
+(0.5), 238,221,203,163,147,121,59.
Compound 1-j: Pterodontoside F [pterodontoside F, 1 α-(β-D-glucopyranosyloxy)-
Enantio-eudesma-4 β, 11-diol]; Colourless powder (methyl alcohol), 196～198 ℃ of fusing points; Mass spectrum EIMS:256[M-glucosyl group]
+(2), 238,221,203,163,147,121,107,59.
Adopt mtt assay to measure the restraining effect of the pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the formula (1) to the growth of HepG2.2.15 cell.The toxic experimental result of specimen pair cell shows that the formula of extracting (1) compound does not have obvious restraining effect to the growth of HepG2.2.15 cell under experimental concentration from Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip..Measure the restraining effect of eudesmane type sesquiterpene derivative to HBV: experimental result shows that the formula of extracting (1) compound has the effect of significant inhibition HBV from Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip..Its hepatitis B surface antigen to HepG2.2.15 emiocytosis (HBsAg) and duplicating of hepatitis B virus thymus nucleic acid (HBV-DNA) have significant inhibitory effect, and prompting type (1) compound has the characteristics of drug safety and highly efficient anti-virus.Therefore, according to the inventor's research, the formula of extracting from Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip. (1) compound can be used for the treatment of the hepatitis B virus infection disease and be used to prepare the medicine of treatment hepatitis B virus infection disease.In order to understand essence of the present invention better, use formula (1) compound to the HepG2.2.15 cell growth inhibition and to the result of the restraining effect of the duplicating test of the HBsAg of HepG2.2.15 emiocytosis and HBV-DNA below respectively, its new purposes in pharmacy field is described.Embodiment has provided the part activity data of the pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the formula (1).Mandatory declaration, embodiments of the invention are to be used to illustrate the present invention rather than limitation of the present invention.Root a tree name essence of the present invention all belongs to the scope of protection of present invention to the simple modifications that the present invention carries out.
Embodiment 1: formula (1) compound is to the restraining effect of the hepatitis B surface antigen(HBsAg) (HBsAg) of HepG2.2.15 emiocytosis
1) cell cultures:
In containing 10% inactivated fetal bovine serum, 100U/ml penicillin and 100 μ g/ml Streptomycin sulphates in the DMEM substratum of 100 μ g/mlG418, are put 37 ℃, 5%CO with the HepG2.2.15 cell cultures
2, cultivate in the incubator of 100% relative humidity.
2) adopt mtt assay to measure the restraining effect of formula (1) compound to the growth of HepG2.2.15 cell:
The HepG2.2.15 cell of taking the logarithm vegetative period falls cell dilution with substratum and becomes 1 * 10
5/ ml is inoculated in 96 porocyte culture plates, every hole 100 μ l, and at 37 ℃, 5%CO
2, cultivate formula (1) compound that adds after 24 hours with the substratum dilution in the incubator of 100% relative humidity, concentration is respectively 1000 μ g/ml, 200 μ g/ml, 40 μ g/ml and 8 μ g/ml, every hole 200 μ l, each concentration is established three multiple holes, places 37 ℃, 5%CO
2, cultivate in the incubator of 100% relative humidity, cultivate after 72 hours, every hole adds 5mg/ml MTT reagent 10 μ l, continues to cultivate 4 hours, discards substratum, every hole adds DMSO 200 μ l, with vibrator vibration 20 minutes, measures the OD value with microplate reader under the 570nm wavelength.With the culture hole that only adds substratum is control wells.
Inhibiting rate (%)=(control wells OD value-experimental group OD value)/control wells OD value * 100%.The experiment triplicate.
The pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the mensuration formula (1) is to the restraining effect of hepatitis B surface antigen(HBsAg) (HBsAg).The HepG2.2.15 cell of taking the logarithm vegetative period becomes 1 * 10 with substratum with cell dilution
5/ ml is inoculated in 96 porocyte culture plates, every hole 100 μ l, and at 37 ℃, 5%CO
2, cultivate formula (1) compound that adds after 24 hours with the substratum dilution in the incubator of 100% relative humidity, concentration is respectively 100 μ g/ml, 20 μ g/ml and 40 μ g/ml, every hole 200 μ l, each concentration is established three multiple holes, places 37 ℃, 5%CO
2, cultivate in the incubator of 100% relative humidity, changed the substratum that contains the same concentrations sample in per 4 days, with the substratum equal-volume mixing that swaps out of same sample one concentration, as testing sample.With hepatitis B surface antigen(HBsAg) (HBsAg) concentration in the ELISA kit measurement substratum, represent with P/N; With the positive contrast of lamivudine (3-TC).
3) experimental result
The example that experimental result is as shown in table 1, the formula of extracting from Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip. (1) compound has the effect of significant inhibition hepatitis B surface antigen(HBsAg) (HBsAg).It is to the no obvious restraining effect of HepG2.2.15 cell growth, all is higher than lamivudine but the hepatitis B surface antigen(HBsAg) HBsAg of HepG2.2.15 emiocytosis is suppressed activity under high, medium and low dosage.
Table 1 formula (1) compound is to HepG2.2.15 excretory hepatitis B surface antigen(HBsAg) (HBsAg) inhibiting rate (%)
| Sample number into spectrum | Concentration (μ g/mL) | 4 days | 8 days |
| HBsAg inhibiting rate (%) | HBsAg inhibiting rate (%) | ||
| Compound 1-a | 100 20 4 | 30.03 / / | 35.98 32.30 / |
| Compound 1-c | 100 20 4 | 24.70 / / | 22.63 19.59 / |
| Compound 1-j | 100 20 4 | 17.68 / / | 51.45 34.04 32.88 |
| 3TC (lamivudine) | 100 20 4 | 28.12 / / | 14.7 / / |
This embodiment presentation of results: the pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the formula (1) has significant inhibitory effect at the 8th day hepatitis B surface antigen(HBsAg) (HBsAg) to HepG2.2.15 emiocytosis, can expect and develop into the medicine that reduces hepatitis B surface antigen(HBsAg), control Type B viral hepatitis symptom.
Embodiment 2: the restraining effect that formula (1) compound duplicates the hepatitis B virus thymus nucleic acid (HBV-DNA) of HepG2.2.15 emiocytosis
1) cell cultures:
Method is with embodiment 1.
2) adopt mtt assay to measure the restraining effect of the pure and mild glycoside compound compound of mapping eudesmane type sesquiterpene shown in the formula (1) to the growth of HepG2.2.15 cell: method is with embodiment 1.
3) the pure and mild glycoside compound compound of the mapping eudesmane type sesquiterpene shown in the mensuration formula (1) restraining effect that hepatitis B virus thymus nucleic acid (HBV-DNA) is duplicated.The HepG2.2.15 cell of taking the logarithm vegetative period becomes 1 * 10 with substratum with cell dilution
5/ ml is inoculated in 96 porocyte culture plates, every hole 100 μ l, and at 37 ℃, 5%CO
2Cultivate the pure and mild glycoside compound compound of mapping eudesmane type sesquiterpene that adds after 24 hours with shown in the formula (1) of substratum dilution in the incubator of 100% relative humidity, concentration is respectively 100 μ g/ml, 20 μ g/ml and 40 μ g/ml, every hole 200 μ l, each concentration is established three multiple holes, places 37 ℃, 5%CO
2, cultivate in the incubator of 100% relative humidity, changed the substratum that contains the same concentrations sample in per 4 days, with the substratum equal-volume mixing that swaps out of the same concentration of same sample, as testing sample.Measure HBV-DNA concentration in the substratum with the HBV-DNA quantitative PCR kit in the time of the 8th day.With the positive contrast of lamivudine (3-TC).
4) experimental result
Experimental result illustrates as shown in table 2, the formula of from Wingedtooth Laggera Herb or Laggera alata (Roxb.) Sch.-Bip., extracting (1) compound Three Represents composition 1-a, and 1-c and 1-j all have the effect that potent inhibition hepatitis B virus thymus nucleic acid (HBV-DNA) duplicates.
The inhibiting rate (%) that table 2 formula (1) compound duplicated the HBV-DNA of HepG2.2.15 cell in the time of the 8th day
| Sample number into spectrum | Concentration (μ g/mL) | Inhibiting rate (%) |
| 1-a | 100 20 4 | 73.46 / / |
| 1-c | 100 20 4 | 79.45 76.65 23.49 |
| 1-j | 100 20 4 | 82.99 67.94 59.24 |
| 3TC (lamivudine) | 100 20 4 | 84.78 75.16 67.52 |
This embodiment presentation of results: the pure and mild glycoside compound of mapping eudesmane type sesquiterpene shown in the formula (1) has great restraining effect to duplicating of hepatitis B virus thymus nucleic acid (HBV-DNA), and it suppresses activity to duplicating of hepatitis B viruses (HBV)-DNA when heavy dose of (100 μ g/mL) the strongest.Belong to potent non-nucleoside and suppress the hepatitis B virus natural product, be worth further paying close attention to and further investigation, and can expect that optimal development is to suppress the medicine of hepatitis B viruses (HBV) dna replication dna.
Claims (7)
1. class mapping eucalyptus alkanols sesquiterpenoid as the formula (1) is to the inhibition activity of the hepatitis B surface antigen (HBsAg) of HepG2.2.15 emiocytosis;
Wherein, R
1, R
2, R
3, R
4, R
5Can be identical or different, can be hydrogen, hydroxyl, contain alkoxyl group, the halogen of 1～8 carbon, also can be replacement or unsubstituted five-carbon sugar or the hexose that links with any configuration and eucalyptus alkane skeleton.
2. described formula (1) compound of claim 1 inhibition activity that the hepatitis B virus thymus nucleic acid (HBV-DNA) in the HepG2.2.15 cell is duplicated.
3. according to claim 1～2, have mapping eucalyptus alkanols sesquiterpenoid and pharmaceutical salts and the solvate thereof shown in the formula (1), these mapping eucalyptus alkanols sesquiterpenoids specifically:
Compound 1-a: pterodondiol (pterodondiol, 4 β, 11-dihydroxyl-mapping-eucalyptus alkane);
Compound 1-b: Wingedtooth Laggera Herb triol first (pterodontriolA, 2 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-c: Pterodontriol B (pterodontriolB, 1 α, 4 β, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-d: Wingedtooth Laggera Herb triol third (pterodontriolC, 4 β, 8 α, 11-trihydroxy--mapping-eucalyptus alkane);
Compound 1-e: Wingedtooth Laggera Herb tetrol (pterodontetraol, 1 α, 2 β, 4 β, 11-tetrahydroxy-mapping-eucalyptus alkane);
Compound 1-f:4 β, 9 α, 11-trihydroxy--mapping-eucalyptus alkane (4 β, 9 α, 11-triol-enantio-eudesmane);
Compound 1-g: Wingedtooth Laggera Herb glycosides C (pterodontosideC, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-11-ol);
Compound 1-h: Wingedtooth Laggera Herb glycosides D (pterodontosideD, 11-(β-D-glucopyranosyloxy)-the enantio-eudesma-4 beta-ol);
Compound 1-i: Wingedtooth Laggera Herb glycosides E (pterodontosideE, 4 β-(β-D-glucopyranosyloxy)-enantio-eudesma-1 α, 11-diol);
Compound 1-j: Pterodontoside F (pterodontosideF, 1 α-(β-D-glucopyranosyloxy)-enantio-eudesma-4 β, 11-diol);
4. according to claim 1～3, formula (1) compound is used to prevent and treat the purposes of hepatitis B, reduction hepatitis B surface antigen.
5. be used to suppress the pharmaceutical composition that hepatitis B virus thymus nucleic acid (HBV-DNA) duplicated, reduced hepatitis B surface antigen according to what claim 4 a kind of contained formula (1) compound, it contains the formula as activeconstituents (1) compound for the treatment of significant quantity, perhaps its pharmacologically acceptable salt or solvate and pharmaceutically acceptable auxiliaries.
6. according to the pharmaceutical composition of claim 5, it can be that tablet, capsule, injection, aerosol, suppository, film, pill, paster agent, subcutaneous planting bury agent, externally-applied liniment, oral liquid or ointment, can also adopt the known controlled release of modern pharmaceutical circle or slow release type or nanometer formulation.
7. according to the preparation of formula (1) compound of claim 1～6, it is characterized in that: separation and purification from plant, preferably from feverfew, obtain, most preferably from composite family Laggera alata (Roxb.) Sch.-Bip. platymiscium, obtain.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100538274A CN100497279C (en) | 2006-10-13 | 2006-10-13 | Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100538274A CN100497279C (en) | 2006-10-13 | 2006-10-13 | Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1935762A true CN1935762A (en) | 2007-03-28 |
| CN100497279C CN100497279C (en) | 2009-06-10 |
Family
ID=37953534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100538274A Expired - Fee Related CN100497279C (en) | 2006-10-13 | 2006-10-13 | Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100497279C (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104804014A (en) * | 2015-03-27 | 2015-07-29 | 云南民族大学 | Icetexane type diterpene dimer compound as well as preparation method and application thereof |
| CN104844616A (en) * | 2015-03-27 | 2015-08-19 | 云南民族大学 | Icetexane type C18 norditerpenoid compound, preparation method therefor and application thereof |
| CN106432380A (en) * | 2015-08-04 | 2017-02-22 | 成都康弘制药有限公司 | New sesquiterpene glycoside compound, preparation method and uses thereof |
| CN109200036A (en) * | 2017-07-05 | 2019-01-15 | 广州医科大学附属第医院 | A kind of drug and its preparation and preparation method for preventing and treating influenza |
| CN112898358A (en) * | 2021-01-30 | 2021-06-04 | 河南中医药大学 | New compound NBY-4 extracted from folium Arctii and having antiinflammatory activity, and its preparation method and application |
| CN115583981A (en) * | 2022-10-10 | 2023-01-10 | 西北农林科技大学 | Eudesmane type sesquiterpene glycoside compound, pittosporum ovatum extract containing same and application thereof |
-
2006
- 2006-10-13 CN CNB2006100538274A patent/CN100497279C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104804014A (en) * | 2015-03-27 | 2015-07-29 | 云南民族大学 | Icetexane type diterpene dimer compound as well as preparation method and application thereof |
| CN104844616A (en) * | 2015-03-27 | 2015-08-19 | 云南民族大学 | Icetexane type C18 norditerpenoid compound, preparation method therefor and application thereof |
| CN106432380A (en) * | 2015-08-04 | 2017-02-22 | 成都康弘制药有限公司 | New sesquiterpene glycoside compound, preparation method and uses thereof |
| CN106432380B (en) * | 2015-08-04 | 2019-05-24 | 成都康弘制药有限公司 | A kind of new sequiterpene glucoside compound, preparation method and the usage |
| CN109200036A (en) * | 2017-07-05 | 2019-01-15 | 广州医科大学附属第医院 | A kind of drug and its preparation and preparation method for preventing and treating influenza |
| CN112898358A (en) * | 2021-01-30 | 2021-06-04 | 河南中医药大学 | New compound NBY-4 extracted from folium Arctii and having antiinflammatory activity, and its preparation method and application |
| CN112898358B (en) * | 2021-01-30 | 2022-06-17 | 河南中医药大学 | A new compound NBY-4 with anti-inflammatory activity extracted from burdock leaves and its preparation method and application |
| CN115583981A (en) * | 2022-10-10 | 2023-01-10 | 西北农林科技大学 | Eudesmane type sesquiterpene glycoside compound, pittosporum ovatum extract containing same and application thereof |
| CN115583981B (en) * | 2022-10-10 | 2024-04-12 | 西北农林科技大学 | Eucalyptane-type sesquiterpenoid glycoside compounds, Pittosporum ovatum extracts containing the same and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100497279C (en) | 2009-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69624813T2 (en) | ROBUSTAFLAVON AND ITS DERIVATIVES AS AN ANTIVIRAL AGENT | |
| EP1421933A1 (en) | Use of stilbene compounds in preparing medicaments for treating or preventing diabetes and diseases associated with retrovirus | |
| US5908857A (en) | Agent for the treatment of infections | |
| CN102727563A (en) | HIV latency-resistant effective part of euphorbia and use thereof | |
| CN100497279C (en) | Pharmaceutical use of ent-eudesmane alcohol type sesquiterpene for inhibiting hepatitis virus | |
| CN104490908B (en) | A kind of medical composition and its use being derived from the Cortex Eucommiae | |
| EP2116253A1 (en) | Novel phyllanthus extract | |
| EP0348509A1 (en) | Anti-retroviral drug | |
| WO2010040254A1 (en) | The use of flavones from radix scutellariae in manufacture of medicaments for treating enterovirus infection | |
| CN100482217C (en) | Medical usage of 2beta-hydroxyilicicacid in inhibiting hepatitis B | |
| CN1927197B (en) | Medical use of 1beta-keto-5, 11(13)-diene eudesmane-12-acid for inhibiting hepatitis B virus | |
| CN113521060A (en) | Application of NEEDOLIDE in resisting novel coronavirus | |
| CN100413495C (en) | Medical use of 2 alpha, 3 beta-dihydroxy-5, 11(13)- diallyl eudesmane-12 acid for inhibiting hepatitis B virus | |
| CN1935131B (en) | Pharmaceutical use of 1 beta-hydroxy ilexolic acid for inhibiting hepatitis virus | |
| US12403125B2 (en) | Use of Ovatodiolide against SARS-CoV-2 | |
| TWI754260B (en) | Use of ovatodiolide against sars-cov-2 | |
| CN101590072B (en) | Application of calycosin-7-O-beta-D-glucopyranoside or salt thereof in resisting AIDS | |
| CN110818613B (en) | Carbazole compound, preparation method thereof and application thereof in anti-HIV (human immunodeficiency virus) medicines | |
| CN111617076B (en) | Compound pharmaceutical composition containing arbidol hydrochloride and application thereof | |
| WO2014129884A2 (en) | Composition with inhibitory effect on viral integrase activity | |
| CN102727551A (en) | Use of effective part of traditional Chinese medicine in HIV latency-resistant treatment | |
| CN100494157C (en) | Eudesmane type sesquiterpenes acid and application thereof | |
| CN1303673A (en) | Application of sophocarpine in preparation of medicine for curing coxsackievirus B myocarditis and its preparation method | |
| CN113082080B (en) | Application of illicium plants or extracts thereof in preparation of anti-animal virus drugs | |
| CN110840885B (en) | Anti-nasopharyngeal cancer application of vegetarian calyxin |
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 | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090610 Termination date: 20101013 |