TWI535439B - A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance - Google Patents
A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance Download PDFInfo
- Publication number
- TWI535439B TWI535439B TW103115989A TW103115989A TWI535439B TW I535439 B TWI535439 B TW I535439B TW 103115989 A TW103115989 A TW 103115989A TW 103115989 A TW103115989 A TW 103115989A TW I535439 B TWI535439 B TW I535439B
- Authority
- TW
- Taiwan
- Prior art keywords
- hepatitis
- drug
- virus
- resistant
- virus strain
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 36
- 229940079593 drug Drugs 0.000 title claims description 28
- 206010059866 Drug resistance Diseases 0.000 title claims 2
- 208000006454 hepatitis Diseases 0.000 title claims 2
- 231100000283 hepatitis Toxicity 0.000 title claims 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 title description 2
- 229930003944 flavone Natural products 0.000 title description 2
- 150000002212 flavone derivatives Chemical class 0.000 title description 2
- 235000011949 flavones Nutrition 0.000 title description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 241000700721 Hepatitis B virus Species 0.000 claims description 54
- 229930003935 flavonoid Natural products 0.000 claims description 22
- 235000017173 flavonoids Nutrition 0.000 claims description 22
- 208000002672 hepatitis B Diseases 0.000 claims description 20
- -1 methoxy flavonoid compound Chemical class 0.000 claims description 18
- 210000004185 liver Anatomy 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 9
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 claims description 8
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 claims description 8
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 claims description 8
- 235000012661 lycopene Nutrition 0.000 claims description 8
- 239000001751 lycopene Substances 0.000 claims description 8
- 229960004999 lycopene Drugs 0.000 claims description 8
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 claims description 8
- OBIOZWXPDBWYHB-UHFFFAOYSA-N Nobiletin Natural products C1=CC(OC)=CC=C1C1=C(OC)C(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 OBIOZWXPDBWYHB-UHFFFAOYSA-N 0.000 claims description 7
- MRIAQLRQZPPODS-UHFFFAOYSA-N nobiletin Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 MRIAQLRQZPPODS-UHFFFAOYSA-N 0.000 claims description 7
- 239000001053 orange pigment Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000000694 effects Effects 0.000 description 17
- 239000000427 antigen Substances 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 15
- 108091007433 antigens Proteins 0.000 description 15
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 14
- 230000004083 survival effect Effects 0.000 description 11
- 229960003276 erythromycin Drugs 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 102000002045 Endothelin Human genes 0.000 description 4
- 108050009340 Endothelin Proteins 0.000 description 4
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 4
- 150000002215 flavonoids Chemical class 0.000 description 4
- 241000700605 Viruses Species 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 235000012754 curcumin Nutrition 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ULSUXBXHSYSGDT-UHFFFAOYSA-N tangeretin Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 ULSUXBXHSYSGDT-UHFFFAOYSA-N 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101710142246 External core antigen Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- IECRXMSGDFIOEY-UHFFFAOYSA-N Tangeretin Natural products COC=1C(OC)=C(OC)C(OC)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C=C1 IECRXMSGDFIOEY-UHFFFAOYSA-N 0.000 description 1
- CQIUKKVOEOPUDV-IYSWYEEDSA-N antimycin Chemical compound OC1=C(C(O)=O)C(=O)C(C)=C2[C@H](C)[C@@H](C)OC=C21 CQIUKKVOEOPUDV-IYSWYEEDSA-N 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- CQIUKKVOEOPUDV-UHFFFAOYSA-N citrinine Natural products OC1=C(C(O)=O)C(=O)C(C)=C2C(C)C(C)OC=C21 CQIUKKVOEOPUDV-UHFFFAOYSA-N 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本發明係關於一種甲氧基黃酮類化合物之用途，特別關於一種用以製備B型肝炎治療用藥物之用途。 The present invention relates to the use of a methoxy flavonoid, and more particularly to the use of a medicament for the treatment of hepatitis B.
B型肝炎(hepatitis B)係為一種國人常見之疾病，成人中約有15%體內帶有B型肝炎病毒(hepatitis B virus)，且B型肝炎病毒造成之慢性肝病、肝硬化(cirrhosis)及肝癌(hepatocellular carcinoma)等衍生疾患，更是位居國人十大死因之榜首。 Hepatitis B is a common disease in Chinese. About 15% of adults have hepatitis B virus, and chronic liver disease, cirrhosis caused by hepatitis B virus and Derived diseases such as liver cancer (hepatocellular carcinoma) are the top ten causes of death among Chinese people.
肝安能(Lamivudine)為一種用以治療B型肝炎之習用藥物，肝安能係屬於胞苷類似物(cytidine analogue)，可以抑制B型肝炎病毒之反轉錄酶，進而抑制B型肝炎病毒之複製。惟，肝安能用於治療慢性B型肝炎時，卻容易因為療程較長，使B型肝炎病毒發生突變，而產生抗藥性病毒株，可能會使肝安能之治療效果變得不佳，是以，確實仍有必要發展新的抗B型肝炎藥物。 Lamivudine is a conventional drug for the treatment of hepatitis B. The liver energy system belongs to the cytidine analogue, which can inhibit the reverse transcriptase of hepatitis B virus and inhibit the hepatitis B virus. copy. However, when liver ampoules can be used to treat chronic hepatitis B, it is easy to cause a mutation in the hepatitis B virus due to a long course of treatment, and a drug-resistant virus strain may cause poor healing effects of the liver. Therefore, it is still necessary to develop new anti-hepatitis B drugs.
本發明之主要目的係提供一種甲氧基黃酮類化合物之用途，係抑制B型肝炎病毒之存活，以治療B型肝炎者。 The main object of the present invention is to provide a use of a methoxy flavonoid for inhibiting the survival of hepatitis B virus for the treatment of hepatitis B.
為達到前述發明目的，本發明所運用之技術手段及藉由該技 術手段所能達到之功效包含有：一種甲氧基黃酮類化合物用以製備治療抗藥性B型肝炎之藥物之用途，其中，該甲氧基黃酮類化合物係選自由川陳皮素及橘紅素所組成之群組。 In order to achieve the aforementioned object of the invention, the technical means utilized by the present invention and by the technique The efficacies can be achieved by the use of a methoxy flavonoid for the preparation of a medicament for the treatment of drug-resistant hepatitis B, wherein the methoxyflavonoid is selected from the group consisting of nobiletin and erythromycin. The group that makes up.
本發明之甲氧基黃酮類化合物用以製備治療抗藥性B型肝炎之藥物之用途，其中，該甲氧基黃酮類化合物係以一有效劑量投予一所需個體，以治療該所需個體之抗藥性B型肝炎。 The use of the methoxyflavonoid compound of the present invention for preparing a medicament for treating drug-resistant hepatitis B, wherein the methoxyflavonoid compound is administered to a desired individual in an effective dose to treat the desired individual Drug-resistant hepatitis B.
本發明之甲氧基黃酮類化合物用以製備治療抗藥性B型肝炎之藥物之用途，其中，該甲氧基黃酮類化合物為川陳皮素，且該有效劑量較佳係為31.1~62.1μM；或者，該甲氧基黃酮類化合物為橘紅素，且該有效劑量較佳係為33.6~67.1μM。 The methoxy flavonoid compound of the present invention is used for the preparation of a medicament for treating drug-resistant hepatitis B, wherein the methoxy flavonoid compound is nobiletin, and the effective dose is preferably 31.1 to 62.1 μM; Alternatively, the methoxyflavonoid compound is orange pigment, and the effective dose is preferably 33.6 to 67.1 μM.
本發明之甲氧基黃酮類化合物係藉由抑制B型肝炎病毒之存活，清除體內之B型肝炎病毒，可以治療B型肝炎，進而達到防止慢性肝病、肝硬化、肝代償不全及肝癌等疾病之發生的功效。 The methoxy flavonoid compound of the present invention can treat hepatitis B by inhibiting the survival of hepatitis B virus and removing hepatitis B virus in the body, thereby preventing diseases such as chronic liver disease, liver cirrhosis, liver insufficiency and liver cancer. The effect of the occurrence.
第1圖：係本發明川陳皮素之化學結構式。 Fig. 1 is a chemical structural formula of the invention.
第2圖：係本發明橘紅素之化學結構式。 Fig. 2 is a chemical structural formula of the orange pigment of the present invention.
第3a圖：係投予本發明甲氧基黃酮類化合物之混合物對B型肝炎病毒株之B肝表面抗原的影響結果柱狀圖。 Fig. 3a is a histogram showing the effect of a mixture of the methoxylated flavonoids of the present invention on the hepatitis B surface antigen of the hepatitis B virus strain.
第3b圖：係投予本發明甲氧基黃酮類化合物之混合物對B型肝炎病毒株之e抗原的影響結果柱狀圖。 Fig. 3b is a bar graph showing the effect of the mixture of the methoxylated flavonoids of the present invention on the e antigen of the hepatitis B virus strain.
第4a圖：係投予本發明川陳皮素對B型肝炎病毒株之B肝表面抗原的影響結果柱狀圖。 Fig. 4a is a histogram showing the effect of administration of the curcumin on the B liver surface antigen of the hepatitis B virus strain of the present invention.
第4b圖：係投予本發明川陳皮素對B型肝炎病毒株之e抗原的影響 結果柱狀圖。 Figure 4b: Effect of administration of the endothelin of the present invention on the e antigen of hepatitis B virus strain Results histogram.
第5a圖：係投予本發明橘紅素對B型肝炎病毒株之B肝表面抗原的影響結果柱狀圖。 Fig. 5a is a bar graph showing the effect of administration of the erythromycin of the present invention on the B liver surface antigen of the hepatitis B virus strain.
第5b圖：係投予本發明橘紅素對B型肝炎病毒株之e抗原的影響結果柱狀圖。 Figure 5b is a bar graph showing the effect of administration of the erythromycin of the present invention on the e antigen of the hepatitis B virus strain.
為讓本發明之上述及其他目的、特徵及優點能更明顯易懂，下文特舉本發明之較佳實施例，並配合所附圖式，作詳細說明如下：本發明之甲氧基黃酮類化合物(polymethoxylated flavone，簡稱PMF)，係供製備治療B型肝炎之藥物，藉由抑制B型肝炎病毒之存活，進而清除生物體體內之B型肝炎病毒。 The above and other objects, features, and advantages of the present invention will become more apparent from the aspects of the invention. Polymethoxylated flavone (PMF) is a drug for the preparation of hepatitis B virus, which can eliminate the hepatitis B virus in the living body by inhibiting the survival of the hepatitis B virus.
本發明之甲氧基黃酮類化合物係可以萃取自柑橘類水果之果皮，或者是市面上可以購得之化學合成產物，其中，請參照第1及2圖所示，該甲氧基黃酮類化合物較佳係可以選自由川陳皮素(nobiletin)及橘紅素(tangeretin)所組成之群組。 The methoxyflavonoid compound of the present invention can be extracted from the peel of citrus fruits or a commercially available chemical synthesis product, wherein, as shown in Figures 1 and 2, the methoxy flavonoid compound is more The best line may be selected from the group consisting of nobiletin and tangeretin.
本發明之甲氧基黃酮化合物係能夠以一有效劑量，供投予一所需個體，以抑制B型肝炎病毒之存活，進而清除生物體體內之B型肝炎病毒，其中，該甲氧基黃酮類化合物為川陳皮素時，該有效劑量較佳係為31.1~62.1μM；或者，該甲氧基黃酮類化合物為橘紅素時，該有效劑量較佳係為33.6~67.1μM。 The methoxylated flavonoid compound of the present invention can be administered to a desired individual at an effective dose to inhibit the survival of the hepatitis B virus, thereby removing the hepatitis B virus in the living body, wherein the methoxylated flavonoid When the compound is citrinin, the effective dose is preferably 31.1 to 62.1 μM; or when the methoxy flavonoid is orange, the effective dose is preferably 33.6 to 67.1 μM.
為證實本發明之甲氧基黃酮化合物係可以清除B型肝炎病毒，遂進行以下試驗，其中，以下試驗除選用野生型B型肝炎病毒株外，另選用對習用藥物肝安能具有抗藥性之抗藥性B型肝炎病毒株進行試驗，於此先行敘明。 In order to confirm that the methoxylated flavonoid compound of the present invention can eliminate the hepatitis B virus, the following test is carried out. Among them, the following test is in addition to the wild type hepatitis B virus strain, and the drug is resistant to the conventional drug. The drug-resistant hepatitis B virus strain was tested and described first.
(A)本發明包含川陳皮素及橘紅素之甲氧基黃酮類化合物(A) The present invention comprises methoxyflavonoids of nobiletin and erythromycin 清除B型肝炎病毒之效果Clear the effect of hepatitis B virus
請參照第1表所示，本試驗係選用甲氧基黃酮類化合物之混合物(簡稱PMF)〔購自JC Nutraceutics Inc.，LOT#PMF-67606-30-NT、PRODUCT#2307，其中包含≧16%之川陳皮素及≧14%之橘紅素〕，分別以不同濃度之PMF處理野生型B型肝炎病毒株及抗藥性B型肝炎病毒株48小時後，以ELISA之方式偵測各組培養液之B肝表面抗原(HBsAg)及e抗原(HBeAg)含量，其結果分別如第3a及3b圖所示。 Please refer to Table 1, which is a mixture of methoxy flavonoids (PMF) [purchased from JC Nutraceutics Inc., LOT#PMF-67606-30-NT, PRODUCT#2307, including ≧16 After treatment with wild-type hepatitis B virus strain and drug-resistant hepatitis B virus strain for 48 hours, different concentrations of PMF were used to detect each group of culture medium by ELISA. The contents of B liver surface antigen (HBsAg) and e antigen (HBeAg) are shown in Figures 3a and 3b, respectively.
請參照第3a圖所示，添加濃度為25及12.5μg/mL之PMF，不論是對於野生型B型肝炎病毒株或是抗藥性B型肝炎病毒株，均有良好之抑制效果(如第A3及A4組結果所示)，顯示該包含川陳皮素及橘紅素之甲氧基黃酮類化合物之混合物係可以抑制該野生型B型肝炎病毒株及該抗藥性B型肝炎病毒株之存活，以達到清除B型肝炎病毒之功效；又，請參照第3b圖所示，PMF處理並不影響各組培養液所含之e抗原含量，是以，該包含川陳皮素及橘紅素之甲氧基黃酮類化合物之混合物並不會影響B型肝炎病毒株之複製。 Please refer to Figure 3a to add PMF at a concentration of 25 and 12.5 μg/mL, which has a good inhibitory effect on wild-type hepatitis B virus strain or drug-resistant hepatitis B virus strain (eg, A3). And the result of the A4 group), showing that the mixture containing the methoxy flavonoids of travertine and lycopene can inhibit the survival of the wild type hepatitis B virus strain and the drug resistant hepatitis B virus strain, To achieve the effect of clearing hepatitis B virus; also, as shown in Figure 3b, PMF treatment does not affect the e antigen content contained in each group of culture medium, so that the methoxy group containing chuanshen and erythromycin The mixture of flavonoids does not affect the replication of the hepatitis B virus strain.
為了證實本發明川陳皮素及橘紅素具有清除B型肝炎病毒之效果，續分別以川陳皮素及橘紅素處理B型肝炎病毒株，其結果如下所示。 In order to confirm that the curcumin and the orange pigment of the present invention have the effect of eliminating the hepatitis B virus, the hepatitis B virus strain was treated with the endothelin and the orange pigment, respectively, and the results are shown below.
(B)本發明川陳皮素清除B型肝炎病毒之效果(B) Effect of the method of removing the hepatitis B virus by the method of the invention
本試驗係以不同濃度川陳皮素(購自Sigma)進行試驗，試驗流程同上所述，各組培養液之B肝表面抗原及e抗原含量分別如第4a及4b圖所示。 The test was carried out with different concentrations of nobiletin (purchased from Sigma). The test procedure was as described above. The B liver surface antigen and e antigen content of each group of culture solutions are shown in Figures 4a and 4b, respectively.
請參照第4a圖所示，添加濃度為62.1及31.1μM之川陳皮素，不論是對於野生型B型肝炎病毒株或是抗藥性B型肝炎病毒株，均有良好之抑制效果(如第B3及B4組結果所示)，顯示本發明川陳皮素係可以抑制該野生型B型肝炎病毒株及該抗藥性B型肝炎病毒株之存活，以達到清除B型肝炎病毒之功效；又，請參照第4b圖所示，川陳皮素處理並不影響各組培養液所含之e抗原含量，是以，本發明川陳皮素並不會影響B型肝炎病毒株之複製。 Please refer to Figure 4a to add a concentration of 62.1 and 31.1 μM of nobiletin, which has a good inhibitory effect on wild-type hepatitis B virus strain or drug-resistant hepatitis B virus strain (such as B3). And the results of the B4 group), which shows that the in vitro dermatanin system of the present invention can inhibit the survival of the wild-type hepatitis B virus strain and the drug-resistant hepatitis B virus strain, thereby achieving the effect of clearing the hepatitis B virus; Referring to Fig. 4b, the treatment of the endothelin does not affect the e antigen content contained in each group of culture liquid, so that the invention has no effect on the replication of the hepatitis B virus strain.
(C)本發明橘紅素清除B型肝炎病毒之效果(C) Effect of the invention on the removal of hepatitis B virus by erythromycin
續以不同濃度橘紅素(購自Sigma)進行試驗，試驗流程同上所述，各組培養液之B肝表面抗原及e抗原含量分別如第5a及5b圖所示。 The test was carried out with different concentrations of lycopene (purchased from Sigma). The test procedure was as described above. The B liver surface antigen and e antigen content of each group of culture solutions are shown in Figures 5a and 5b, respectively.
請參照第5a圖所示，添加濃度為67.1及33.6μM之橘紅素，不論是對於野生型B型肝炎病毒株或是抗藥性B型肝炎病毒株，均有良好之抑制效果(如第C3及C4組結果所示)，顯示本發明橘紅素係可以抑制該野生型B型肝炎病毒株及該抗藥性B型肝炎病毒株之存活，以達到清除B型肝炎病毒之功效；又，請參照第5b圖所示，橘紅素處理並不影響各組培養液所含之e抗原含量，是以，本發明橘紅素並不會影響B型肝炎病毒株之複製。 Please refer to Figure 5a for the addition of lycopene at a concentration of 67.1 and 33.6 μM, both for wild-type hepatitis B virus strains and drug-resistant hepatitis B virus strains (eg, C3 and As shown in the results of the group C4, it is shown that the lycopene of the present invention can inhibit the survival of the wild-type hepatitis B virus strain and the drug-resistant hepatitis B virus strain, thereby achieving the effect of clearing the hepatitis B virus; As shown in Fig. 5b, the treatment of lycopene does not affect the content of e antigen contained in each group of culture solutions, so that the erythromycin of the present invention does not affect the replication of the hepatitis B virus strain.
綜合上述試驗結果，不論是川陳皮素、橘紅素，或是包含川陳皮素及橘紅素之甲氧基黃酮類混合物(即前述之PMF)，均可以有效抑制B型肝炎病毒株之存活，因而可以清除生物體內之B型肝炎病毒，以達到治療B型肝炎之功效；此外，針對抗藥性B型肝炎病毒株，川陳皮素、橘紅素仍可以抑制其存活，進而可以作為肝安能之第二線藥物，於肝安能 之投藥導致抗藥性病毒株之產生後，仍可以有效抑制該抗藥性病毒株之存活，而可以有效治療B型肝炎，降低B型肝炎之發生率。 According to the above test results, whether it is chuanshensu, lycopene, or a mixture of methoxy flavonoids containing catechin and lycopene (ie, the aforementioned PMF), it can effectively inhibit the survival of the hepatitis B virus strain, and thus It can remove the hepatitis B virus in the living body to achieve the effect of treating hepatitis B. In addition, for the drug-resistant hepatitis B virus strain, the endothelin and the orange pigment can still inhibit its survival, and thus can be used as the liver safety. Second-line drugs in the liver After the administration of the drug-resistant virus strain, the survival of the drug-resistant virus strain can be effectively inhibited, and the hepatitis B can be effectively treated, and the incidence of hepatitis B can be reduced.
綜合上述，本發明之甲氧基黃酮類化合物係藉由抑制B型肝炎病毒之存活，清除體內之B型肝炎病毒，可以治療B型肝炎，進而達到防止慢性肝病、肝硬化、肝代償不全及肝癌等疾病之發生的功效。 In summary, the methoxy flavonoid compound of the present invention can treat hepatitis B virus by inhibiting the survival of hepatitis B virus and eliminating hepatitis B virus in the body, thereby preventing chronic liver disease, liver cirrhosis, liver decompensation and The effect of the occurrence of diseases such as liver cancer.
雖然本發明已利用上述較佳實施例揭示，然其並非用以限定本發明，任何熟習此技藝者在不脫離本發明之精神和範圍之內，相對上述實施例進行各種更動與修改仍屬本發明所保護之技術範疇，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。 While the invention has been described in connection with the preferred embodiments described above, it is not intended to limit the scope of the invention. The technical scope of the invention is protected, and therefore the scope of the invention is defined by the scope of the appended claims.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW103115989A TWI535439B (en) | 2014-05-05 | 2014-05-05 | A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW103115989A TWI535439B (en) | 2014-05-05 | 2014-05-05 | A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201542202A TW201542202A (en) | 2015-11-16 |
| TWI535439B true TWI535439B (en) | 2016-06-01 |
Family
ID=55220728
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW103115989A TWI535439B (en) | 2014-05-05 | 2014-05-05 | A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TWI535439B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10265298B2 (en) * | 2017-08-22 | 2019-04-23 | Macau University Of Science And Technology | Method of increasing the bioavailability of silybin |
| WO2020052774A1 (en) | 2018-09-14 | 2020-03-19 | F. Hoffmann-La Roche Ag | Flavone derivatives for the treatment and prophylaxis of hepatitis b virus disease |
| CN111617076B (en) * | 2020-06-24 | 2021-09-28 | 江苏吴中医药集团有限公司 | Compound pharmaceutical composition containing arbidol hydrochloride and application thereof |
-
2014
- 2014-05-05 TW TW103115989A patent/TWI535439B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| TW201542202A (en) | 2015-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | In vitro and in vivo anti-hepatitis B virus activities of the lignan niranthin isolated from Phyllanthus niruri L. | |
| You et al. | Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid | |
| Jia et al. | Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells | |
| Hu et al. | Anti-influenza virus effects of crude phenylethanoid glycosides isolated from ligustrum purpurascens via inducing endogenous interferon-γ | |
| Fathy et al. | The antiproliferative effect of mulberry (Morus alba L.) plant on hepatocarcinoma cell line HepG2 | |
| TWI535439B (en) | A use of polymethoxylated flavone for manufacturing drugs against hepatitis b with drug-resistance | |
| Ho et al. | Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines | |
| Fan et al. | Natural-product-mediated autophagy in the treatment of various liver diseases | |
| TWI583389B (en) | Use of kapok water extract | |
| CN101669979B (en) | Artemisia scoparia extractive and production method and applications thereof | |
| Li et al. | Antiviral effects of modified Dingchuan decoction against respiratory syncytial virus infection in vitro and in an immunosuppressive mouse model | |
| Sun et al. | In vitro antiviral activity of Rubia cordifolia aerial part extract against rotavirus | |
| Romero et al. | Effect of cantharidin, cephalotaxine and homoharringtonine on” in vitro” models of Hepatitis B Virus (HBV) and Bovine Viral Diarrhoea Virus (BVDV) replication | |
| TWI595881B (en) | Use of Nanyangshan Sushui Extract | |
| Wang et al. | Antiviral activity of mangiferin from the rhizome of Anemarrhena asphodeloides against herpes simplex virus type 1 | |
| Kawahara et al. | Inhibitory Effect of a Hot‐Water Extract of Leaves of Japanese Big‐Leaf Magnolia (Magnolia obovata) on Rotavirus‐Induced Diarrhea in Mouse Pups | |
| CN106038695A (en) | Use of avocado extract, avocadol B and (2R,4R) -1,2, 4-trihydroxyheptadeca-16-alkyne, and health food containing avocado extract | |
| Keshavarz et al. | Effects and Mechanisms of Silibinin on Influenza A/H1N1 Pathogenesis in a Mouse Model | |
| Malizia et al. | Statins in cirrhosis: the magic pill? | |
| Alavian et al. | Influence of nutrients, bioactive compounds, and plant extracts in liver diseases | |
| CN103623032B (en) | Euphorbiaceae plant (Euphorbiaceae) active substance and its preparation method and application | |
| CN103565800B (en) | Novel application of glycycoumarin in prevention and treatment of alcoholic liver injury | |
| WO2023089862A1 (en) | Stephania cephalantha-derived alkaloid-containing preparation | |
| Zhang et al. | Traditional Chinese medicine compounds modulate signaling pathways to improve cardiac-related pathology | |
| TWI615146B (en) | A use of an extract of asplenium australasicum (j. sm.) hook. |