CN106063802A - Cacumen Myricariae Germanicae effective site, Its Preparation Method And Use - Google Patents
Cacumen Myricariae Germanicae effective site, Its Preparation Method And Use Download PDFInfo
- Publication number
- CN106063802A CN106063802A CN201610262319.0A CN201610262319A CN106063802A CN 106063802 A CN106063802 A CN 106063802A CN 201610262319 A CN201610262319 A CN 201610262319A CN 106063802 A CN106063802 A CN 106063802A
- Authority
- CN
- China
- Prior art keywords
- effective site
- preparation
- cacumen myricariae
- myricariae germanicae
- chromatography
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
- 241001457485 Myricaria bracteata Species 0.000 claims description 21
- 238000002347 injection Methods 0.000 claims description 21
- 239000007924 injection Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 229920001461 hydrolysable tannin Polymers 0.000 claims description 9
- 238000004587 chromatography analysis Methods 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 7
- 239000004615 ingredient Substances 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 241001141189 Myricaria Species 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 235000014265 Tamarix gallica Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000005325 percolation Methods 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- 229920001503 Glucan Polymers 0.000 claims 1
- 241001529246 Platymiscium Species 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 239000000039 congener Substances 0.000 claims 1
- 238000005227 gel permeation chromatography Methods 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- 239000008187 granular material Substances 0.000 claims 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 claims 1
- 239000006187 pill Substances 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000010898 silica gel chromatography Methods 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 208000009386 Experimental Arthritis Diseases 0.000 abstract description 18
- 241001465754 Metazoa Species 0.000 abstract description 16
- 241000699670 Mus sp. Species 0.000 abstract description 7
- 239000002671 adjuvant Substances 0.000 abstract description 5
- 238000002474 experimental method Methods 0.000 abstract description 5
- 241000700159 Rattus Species 0.000 description 27
- 230000000694 effects Effects 0.000 description 24
- 230000008961 swelling Effects 0.000 description 24
- 210000000952 spleen Anatomy 0.000 description 18
- 230000002757 inflammatory effect Effects 0.000 description 17
- 210000001541 thymus gland Anatomy 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 210000002683 foot Anatomy 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 230000001629 suppression Effects 0.000 description 12
- 210000000544 articulatio talocruralis Anatomy 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 11
- 230000037396 body weight Effects 0.000 description 10
- 210000003714 granulocyte Anatomy 0.000 description 10
- 210000005222 synovial tissue Anatomy 0.000 description 10
- 206010003246 arthritis Diseases 0.000 description 9
- 210000000845 cartilage Anatomy 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 230000003448 neutrophilic effect Effects 0.000 description 9
- 206010062049 Lymphocytic infiltration Diseases 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 230000001575 pathological effect Effects 0.000 description 8
- 210000004872 soft tissue Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 102000008186 Collagen Human genes 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 7
- 229920001436 collagen Polymers 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 206010020880 Hypertrophy Diseases 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 4
- 230000003340 mental effect Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000001258 synovial membrane Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229940126680 traditional chinese medicines Drugs 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010007710 Cartilage injury Diseases 0.000 description 3
- 235000002917 Fraxinus ornus Nutrition 0.000 description 3
- 244000182067 Fraxinus ornus Species 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 210000001188 articular cartilage Anatomy 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000037308 hair color Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 210000002437 synoviocyte Anatomy 0.000 description 3
- 210000001835 viscera Anatomy 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 206010023232 Joint swelling Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003356 anti-rheumatic effect Effects 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
- 238000003287 bathing Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 229960002344 dexamethasone sodium phosphate Drugs 0.000 description 2
- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 description 2
- 238000007598 dipping method Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 229930003944 flavone Natural products 0.000 description 2
- 235000011949 flavones Nutrition 0.000 description 2
- 229940074391 gallic acid Drugs 0.000 description 2
- 235000004515 gallic acid Nutrition 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000009916 joint effect Effects 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- 210000001226 toe joint Anatomy 0.000 description 2
- 102000001671 Acid Sensing Ion Channels Human genes 0.000 description 1
- 108010068806 Acid Sensing Ion Channels Proteins 0.000 description 1
- 208000000819 Adrenocortical Hyperfunction Diseases 0.000 description 1
- 241001142920 Apantesis f-pallida Species 0.000 description 1
- 235000004040 Artemisia sieversiana Nutrition 0.000 description 1
- 241001201008 Artemisia sieversiana Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241001490016 Cephalanthera falcata Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 241000218671 Ephedra Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 206010020564 Hyperadrenocorticism Diseases 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 241001111421 Pannus Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 241000208422 Rhododendron Species 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 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 description 1
- 241000830536 Tripterygium wilfordii Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- -1 alcohol Compound Chemical class 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 208000015606 cardiovascular system disease Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 208000013219 diaphoresis Diseases 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 239000002024 ethyl acetate extract Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 210000003026 hypopharynx Anatomy 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007119 pathological manifestation Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 235000015398 thunder god vine Nutrition 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to Cacumen Myricariae Germanicae effective site, its preparation method and treating rheumatism, the purposes of rheumatoid arthritis.Animal experiment proves that, this effective site can suppress Oleum Tiglii to cause mice ear and rat adjuvant or collagen induced arthritis, can be used for preventing and/or treating the purposes of rheumatism, rheumatoid arthritis.
Description
Technical field
The present invention relates to the effective site extracted from tradition Tibetan medicine Cacumen Myricariae Germanicae, including the preparation side of this effective site
Method, containing the pharmaceutical composition of this effective site, and exists containing this effective site and its pharmaceutical composition
Treat the purposes in the medicine of rheumatism, rheumatoid arthritis, the invention belongs to pharmaceutical technology field.
Background technology
Rheumatoid arthritis (Rheumatoid Arthritis, RA) be a kind of with articular synovitis be characterized chronic
Autoimmune disease, is often accompanied by inflammatory cell (T cell, neutrophilic granulocyte, macrophage etc.) and attacks, soaks
Profit, capillary proliferation, articular synovial cells hypertrophy, synovial membrane lower floor synovial membrane thicken formation fine hair shape projection and bone
With pathological changes such as cartilage injurys.This inflammation can cause joint deformity until maimed, and can because of joint pain and
Wear and tear and lose the mobility of part.The feature of RA is hands, the foot multi-joint of Minor articulus, symmetry, invasion and attack
Property arthritis, being often accompanied by organ outside joint, to be involved serum rheumatoid factor (SRF) positive, can cause arthritis
Bitterly, stiff, tired, bone injury, final there is deformity and afunction[1].RA the most generally exists,
Whole world prevalence is about 1～2% according to statistics, and China's prevalence is about 0.5%, if this disease is treated the most in time, by
In cartilage and the destruction of osseous tissue, the RA patient of 70% can be disabled after 2 years, be had a strong impact on Health and Living matter
Amount[2,3]。
At present the drug main of clinical treatment RA to have three classes, i.e. steroidal anti-inflammatory drugs, nonsteroidal antiinflammatory drug and
Improve state of an illness antirheumatic.But steroidal anti-inflammatory drugs life-time service can cause hemo-hyperadrenocorticism comprehensive
Disease, digestive complications, cardiovascular system diseases and osteoporosis, big joint bland necrosis, infection
Deng untoward reaction etc.；Nonsteroidal antiinflammatory drug can control the symptom of RA patient, but little, no on disease impact itself
Affect the course of disease of RA, it is impossible to stoping destruction of joint and organ injury progress, life-time service can bring gastrointestinal tract, kidney
The side reactions such as toxicity, also have damage to articular cartilage；Improve state of an illness antirheumatic and can only improve the state of an illness, alleviate disease
Shape, does not reaches the effect for the treatment of[3,4].Although these medicines above-mentioned can suppress the generation of inflammation, alleviate the disease of RA
Shape, but these medicines of life-time service all may occur in which serious untoward reaction.Consequently found that, develop and develop and more pacify
Entirely, more effectively treatment RA medicine has significant application value.
Cacumen Myricariae Germanicae is conventional Tibetan medicine, and its source is Ramulus et Folium Tamaricis section Myricaria plant Cacumen Myricariae Germanicae Myricaria germanica
L.Desv and belong to the twig of various plants together, is distributed widely in the west such as China Tibet, Qinghai, Gansu, the Inner Mongol
Area, portion.Tibetan medicine name " stupe ", its property put down, sweet-salty, Xin Ganwen, have dispelling wind to relieve the exterior syndrome, dispelling wind and removing obstruction in the collateral,
Rash, cough-relieving, effect of heat-clearing and toxic substances removing[5,6].Cacumen Myricariae Germanicae is mainly used in treating rheumatic arthralgia as tradition Tibetan medicine,
Measles without adequate eruption, pestilence epidemic disease, the diseases such as internal organs are scorchingly hot, laryngopharynx swelling and pain, nosotoxicosis, grasserie, and heat in blood is sick[7], mesh
Front Cacumen Myricariae Germanicae is mainly used in treating rheumatism clinically, cures mainly rheumatic arthritis, rheumatoid arthritis, urgency
Chronic rheumatic arthritis etc.[8].Meanwhile, Cacumen Myricariae Germanicae is also the key agents of multiple compound recipe Tibetan medicine, such as five tastes manna
Dipping dissipates, QIZHENG XIAOTONG TIE etc..It is the bathing preparation that shows unique characteristics of Tibetan medicine that five tastes manna dipping dissipates[9], recorded
In the national drug standards, this compound recipe is by flavour of a drug groups such as Cacumen Myricariae Germanicae, Cacumen et folium sabinae przewalskii, Rhododendron, Artemisia sieversiana Willd., Herba Ephedraes
Becoming, have dispelling wind and removing obstruction in the collateral, diaphoresis is antipruritic, strengthens the effects such as autoimmune, to rheumatic, rheumatoid joint
The diseases such as inflammation have special efficacy[10-12].QIZHENG XIAOTONG TIE cream is made up of the Six-element Tibetan medicine such as Radix Lamiophlomidis Rotatae, Cacumen Myricariae Germanicae, tool
Having activating blood circulation to dissipate blood stasis, reducing swelling and alleviating pain effect, the key agents in its side with anti-inflammatory efficacy is Cacumen Myricariae Germanicae[13].Through being
System consulting literatures finds, both at home and abroad Cacumen Myricariae Germanicae chemical constitution study is concentrated mainly on flavone, gallic acid and three
Terpenoid, in addition with the class such as sterol, long-chain fatty alcohol.To Myricaria plant pharmacology activity research table
Its extract bright has antibacterial action[14], antiinflammatory action[15,16], analgesic activity[17], immunomodulating[18]Exempt from cell
Epidemic disease effect[19], resisting fatigue[20]And antioxidation[21]Etc. multiple pharmacologically active.Despite research report Cacumen Myricariae Germanicae (father-in-law's cloth)
Water extract and ethanol extract have inhibitory activity to SD rat FCA Induced Arthritis[16], its total flavones is to assistant
Agent rats with arthritis has immunoregulation effect[18].Although above research report confirms that Cacumen Myricariae Germanicae closes in treatment
Activity in terms of joint is scorching, but determined by active site be only crude extract, effective ingredient is the most indefinite, this patent
On the basis of previous research work, confirm Cacumen Myricariae Germanicae effective site in terms for the treatment of of arthritis further and have
Effect composition, up to now, has not seen research report and the patent of this aspect.
List of references
1 Song Ya nanmu, Ji Wei. the progress [J] of Tripterygium Wilfordii Polyglycoside rheumatoid arthritis, clinical department of internal medicine magazine, 2009,
26 (10): 663-665.
2 old flying tigers, Yuan Feng comes, Li Xia etc. and several resisting rheumatoid arthritis medicines are to adjuvant arthritis rats articular chondrocytes
The expression impact of Acid-sensing Ion Channels and effect [J], Chinese Clinical pharmacology and therapeutics, 2008,13 (2): 131-137.
3 Wang Bin, Tang Fulin. treating rheumatoid arthritis progress [J], Shanxi Medicine magazine, 2001,30 (1): 34-38.
4 thank and grow, Zeng little Feng. treating rheumatoid arthritis progress [J], and practical general family medicine, 2004,2 (2): 176-177.
The 5 new medical college in Jiangsu. the Chinese medicine voluminous dictionary first volume, Shanghai: Shanghai science tech publishing house, 1998,535.
6 Qinghai Tibet Medical Institute of institute for drug control, Qinghai Province. China's Tibetan medicine volume three, Shanghai: Science and Technology of Shanghai publishing house, 1996:
277～279.
7 Northwest Plateau-organisms Research Inst. of Chinese Academy of Sciences. Tibetan medicine will. Xining: the Qinghai People's Press, 1991.318.
8 Luo Da to. China hide book on Chinese herbal medicine, Beijing: Nationalities Press, 1997:160.
9 beautiful cloudy Deng Gongbu. four doctors's allusion quotation (Tibetan language). the Lhasa Tibet People's Publishing House, 1982:639.
10 Yu you dragon, Cui Zhizhong, A Weitian. Tibetan medicine and pharmacology balneotherapy treatment rheumatoid arthritis 131 example efficacy analysis [J], Chinese and western medicine
In conjunction with magazine, 1989,9 (1): 36.
11 Lee first add. Tibet-medicine Bath treatment rheumatoid arthritis 223 example clinical observation [J]. and National medicine magazine, 1997,3 (2): 15.
12 Zhou little Mei, Chen Qiuhong, Dorje, Yang Quanyu. gold scolds the antiinflammatory action [J] of manna medicinal-bathing particle, the Shanxi traditional Chinese medical science, and 2003,
19 (1): 50-52.
13 Soviet Union's Po Lams, Ma Rong. QIZHENG XIAOTONG TIE pharmacodynamic study [J], Beijing traditional Chinese medical science, 1996,6:57-59.
14 Bao Min, Zeng Yang, meter Qin, Chen Zhenning. antibacterial experiment in vitro research [J] of Tibetan medicine father-in-law's cloth difference extract. Shi Zhen traditional Chinese medical science state
Medicine, 2006,17 (8): 1410-1411.
15 Zeng Yang, Chen Zhenning, Luo Guihua, etc. the impact [J] on acute inflammation model mice superoxide dismutase of the Tibetan medicine father-in-law's cloth.
Shandong journal of Chinese medicine, 2005,24 (4): 236-237.
16 Bao Min, Zeng Yang, Chen Zhenning. the experimental study [J] to SD rat FCA Induced Arthritis of the Tibetan medicine father-in-law's cloth extract. Qinghai
Normal university's journal: natural science edition, 2012,28 (4): 46-48.
17 Zeng Yang, Chen Zhenning, Zhong Liang, etc. Tibetan medicine father-in-law's cloth anti-inflammatory and analgesic effect experimentation [J]. Chinese patent medicine, 2005,27 (5):
614-616。
18 Zeng Yang, Bao Min, Ma Jixiong, etc. father-in-law's cloth total flavones immune regulation mechanism [J] to adjuvant arthritis rats. middle traditional Chinese medicines
Circular of science, 2011,27 (4): 504-507.
19 Zeng Yang, Chen Zhenning, Zhong Liang, etc. impact and the toxicity test thereof of cellular immune function are studied [J] by Tibetan medicine father-in-law's cloth. Qinghai
Normal university's journal: natural science edition, 2005,21 (1): 66-68.
20 Bao Min, Luo Guihua, Zeng Yang, etc. Tibetan medicine father-in-law's cloth to exercised rats superoxide dismutase activity and lipid peroxidation
Impact [J]. Chinese patent medicine, 2005,27 (11): 1348-1350.
21 Cephalanthera falcata (Thunb) Lindl, Luo Guihua, Zeng Yang, etc. the impact [J] on exhausted movemeat mouse cardiac muscle peroxidase enzymes of the Tibetan medicine father-in-law's cloth.
The Sichuan traditional Chinese medical science, 2005,23 (4): 13-14.
Summary of the invention
The invention solves the problems that technical problem is to provide a class Cacumen Myricariae Germanicae effective site, its preparation method, medicine group
Compound and its application in preparation prevention and/or treatment rheumatism, medicine for treating rheumatoid arthritis.
For solving above-mentioned technical problem, the technical scheme is that
The first aspect of technical solution of the present invention is to provide the preparation method of a kind of Cacumen Myricariae Germanicae effective site.
Cacumen Myricariae Germanicae in the present invention, plant origin is the dry twig of Ramulus et Folium Tamaricis section Myricaria plant.Its effective portion
The preparation method of position is as follows:
Step 1). extracting method: by raw medicinal material (Cacumen Myricariae Germanicae) after drying, suitably pulverize, then with molten
Agent is extracted, and the solvent of extraction includes water, alcohols, acetone or water and alcohols or the mixed solvent of acetone.Wherein alcohol
Kind solvent is preferred: the mixed solvent of one or more in methanol, ethanol, propanol or butanol.Water is mixed with alcohol
Compound, for the alcoholic solution of 40-95% (volume ratio)；Extracting method includes: percolation, extract or be heated to reflux to carry
Take；During extraction, solvent load is 5-20 times of medical material weight, and extraction can be carried out, for carrying under dynamic or static state
High extracting efficiency also can be selected for ultrasonic extraction；The temperature extracted can temperature range from room temperature to solvent refluxing
In；Extraction can be carried out continuously or interval is carried out, extraction time 1-4 time.Extracting solution can be selected normal pressure or subtract
Pressure is concentrated to give extractum or non-alcoholic concentrated solution.
Step 2). separation method:
(1) above-mentioned concentrated solution is added suitable quantity of water and make extractum dispersing and dissolving, with petroleum ether (boiling point is 60-90 DEG C)
Extract successively with ethyl acetate, respectively obtain petroleum ether part, Ethyl acetate extract and water position.
(2) by above-mentioned water position through macroporous adsorption resin chromatography, respectively with water, 30% ethanol, 50% ethanol and
95% ethanol elution, the freeze-dried Cacumen Myricariae Germanicae effective site that obtains in each eluting position, preferably 30% ethanol elution
The Cacumen Myricariae Germanicae effective site obtained；Wherein, macroporous adsorbent resin includes D101, HPD-100, HP-20 etc..
The second aspect of technical solution of the present invention is to provide a kind of Cacumen Myricariae Germanicae effective site, described effective site
Prepare according to the preparation method described in first aspect present invention.
Further, the effective ingredient of above-mentioned Cacumen Myricariae Germanicae effective site is hydrolysable tannin compounds.Wherein,
Hydrolysable tannin compounds includes as described below 12 compound:
3rd aspect of technical solution of the present invention is to provide a kind of pharmaceutical composition, described pharmaceutical composition bag
Include the Cacumen Myricariae Germanicae effective site described in the second aspect of effective dose and pharmaceutically acceptable carrier.
This pharmaceutical composition can be prepared according to method well known in the art.Can by by Cacumen Myricariae Germanicae effective site with
One or more pharmaceutically acceptable solid or liquid excipient and/or adjuvant combine, make and be applicable to people and make
Any dosage form.Cacumen Myricariae Germanicae effective site content in its pharmaceutical composition is usually 1-95% (weight
Than).
Additionally, the need to, it is also possible in pharmaceutical preparation, add coloring agent, antioxidant, preservative, perfume (or spice)
Material, correctives, sweeting agent or other materials.
For reaching medication purpose, strengthening therapeutic effect, the medicine of the present invention or pharmaceutical composition can be with any known
Medication be administered.
The compounds of this invention, the dosage of pharmaceutical composition depend on many factors, such as, to prevent or to control
Treat character and the age of the order of severity, patient or animal, sex, body weight, personality and the individual reaction of disease,
Route of administration, administration number of times, therapeutic purposes, therefore the therapeutic dose of the present invention can have change on a large scale.
In general, the using dosage of Chinese materia medica composition of the present invention is known in those skilled in the art.Can be according to this
Actual drug quantity contained in preparation last in invention compound composition, in addition suitable adjustment, with
Reach the requirement of its therapeutically effective amount, complete prevention or the therapeutic purposes of the present invention.
The Cacumen Myricariae Germanicae effective site of the present invention or compositions can be used alone, or with other medicine or suit the medicine to the illness
Medicine merges use.
4th aspect of technical solution of the present invention there is provided Cacumen Myricariae Germanicae effective site in preparation prevention and/or treatment
Rheumatism, rheumatoid arthritis medicine in purposes.
Advantageous Effects:
Animal experiment proves that, the Cacumen Myricariae Germanicae effective site of the present invention can substantially suppress Oleum Tiglii to cause mice ear
The foot swelling caused with rat adjuvant or collagen induced arthritis.This effective site has prevention and/or treatment wind
Wet, the purposes of rheumatoid arthritis.
Accompanying drawing explanation
The preparation flow figure of Fig. 1 Myricaria bracteata effective site.
The UV spectrum of hydrolyzable tannin compounds in Fig. 2 Myricaria bracteata effective site.
In Fig. 3 Myricaria bracteata effective site, the high performance liquid chromatography of hydrolyzable tannin compounds inspects figure.
Fig. 4 Myricaria bracteata effective site effect (note: with model group phase to adjuvant arthritic rats foot swelling
Than * * p < 0.01).
Fig. 5 collagen induced arthritis rat body weight situation of change.
Detailed description of the invention
Example below is used for further illustrating the present invention, but it is not intended that any restriction of the present invention.
Cacumen Myricariae Germanicae effective site
Embodiment 1: the preparation of Myricaria bracteata effective site
Select the dry twig 15kg of Myricaria bracteata (Myricaria bracteata), with 6 times amount ethanol heating
Reflux, extract, 3 times, each 2 hours, extracting solution decompression recycling ethanol was also concentrated to give extractum.Add suitable quantity of water to make
Extractum dispersing and dissolving, extracts successively with petroleum ether and ethyl acetate, respectively obtains petroleum ether part, acetic acid
Ethyl ester position and water position.Water position is filtered, and the macroporous adsorbent resin HP-20 that filtrate is treated separates, respectively
With the water of 8 times amount, 30% ethanol, 50% ethanol and 95% ethanol elution, recovered under reduced pressure 30% ethanol elution portion
Position, freeze-dried i.e. obtains effective site 141.1g.(see Fig. 1)
Embodiment 2: the component analysis of Myricaria bracteata effective site
Effective ingredient in Cacumen Myricariae Germanicae effective site is hydrolysable tannin compounds, and this compounds is by glucose
It is formed by connecting with ester bond or glycosidic bond with gallic acid.
Ultraviolet (UV) spectrum of hydrolysable tannin compounds is typically in the range of 205-224 and 260-283nm
The characteristic absorption peak of 2 UV of display.(see Fig. 2)
The inspection of the effective ingredient hydrolysable tannin compounds in Cacumen Myricariae Germanicae effective site is known method and is used, high-efficient liquid
Phase chromatograph.High-performance liquid chromatogram determination method is for using binary geopressure gradient type of elution, and analyzing chromatographic column is
COSMOSIL 5C18-PAQ Waters (4.6i.d. × 250mm) type, flowing is that A is (containing 2% vinegar mutually
The water of acid) and B (acetonitrile), gradient is 0-1min, 5%B, 1-5min, 5%-15%B, 5-40
Min, 15%-20%B, column temperature is 25 DEG C, and detection wavelength is 280nm.High-efficient liquid phase chromatogram is shown in Fig. 3.
The structural formula that effective ingredient hydrolysable tannin compounds in Myricaria bracteata effective site is corresponding is as follows:
Pharmacological activity test:
Experimental example 1: Myricaria bracteata effective site (SBZ group) suppression Oleum Tiglii causes the test of mice ear.
Kunming mouse is randomly divided into model group, blank group, SBZ group, often group 7.Each administration group
All gavages (ig) give relative medicine 1 time, and dosage 100mg/kg, model group gives equal-volume 0.1%
Tween-80 solution.After 1h, each group mice left ear two sides uniform application 2% Oleum Tiglii sensitization, sensitization 4h
Rear execution, cuts left and right auricle, makes, with the rustless steel card punch of diameter 8mm, the auricle that size is identical, point
Another name quality, using two ear quality differences as swelling.
Oleum Tiglii causes the result of the test of mice ear: the suppression ratio of effective site is 65.2%, and has no dynamic
Thing is dead.Prompting effective site has the anti-inflammatory activity of highly significant.
Conclusion: it is to simulate the model of inflammatory reaction that Oleum Tiglii causes mice otitis, and the present invention is sent out by experimentation
Existing, Myricaria bracteata extracts active site and significantly inhibits mice ear effect, can be used for preparing anti-inflammatory drug.
Experimental example 2: the Myricaria bracteata effective site (SBZ group) effect to rat assist agent arthritis
Laboratory animal: Wistar rat (180 ± 10) g, SPF level, in Military Medical Science Institute's laboratory animal
The heart provides, quality certification SCXK (army) 2007-004.
Test medicine: SBZ component；Dexamethasone sodium phosphate injection (Dex), traditional Chinese medicines group holds raw pharmacy to be had
Limit company (traditional Chinese medicines quasi-word H41020036).
Experimental technique: Wistar rat is randomly divided into model (Model) group, Dex group and SBZ group, often
Group is respectively 10,10,8.Bacillus calmette-guerin vaccine is placed in 57 DEG C of water-bath inactivation 45min, is dissolved in paraffin
With lanoline by 2: 1 solution mixed, the Emulsion that bacillus calmette-guerin vaccine mass concentration is 10mg/ml is made in emulsifying.
After 2 weeks, rat is divided into model group, dexamethasone (0.2mg/kg) group, SBZ (20mg/kg) group, each group
Rat two parapodum girth and the equal no difference of science of statistics of weight.Packet was respectively organized beginning and subcutaneous give relative medicine the same day
10ml/kg, matched group, model group give same volume 0.1% Tween-80 solution, successive administration 15d,
Every day 1 time.Rat two metapedes girth is measured, by 5 grades of point systems to entirely in being administered the 5th, 9,12,15 days
Each joint of body is evaluated, i.e. 0 point, without red and swollen；1 point, toe joint is red and swollen；2 points, toe joint and foot
Sole of the foot swelling；3 points, the sufficient pawl swelling below ankle joint；4 points, the whole foot pawl swelling including ankle joint.
Polyarthritis index (AI, AI=extremities joint scoring sum) is calculated according to appraisal result.It is administered
The dead animal in end, rat takes spleen, thymus is weighed, and calculates index and spleen index, thymus index.Often group takes injection side
Ankle joint, 10% formalin solution soak after with 8% salpeter solution decalcification, through dehydration, waxdip, embedding,
Sections etc. process, and HE dyes, and under light microscopic, (× 100) are observed.
Experimental result: be shown in Table 1, table 2, Fig. 4.
The impact on adjuvant arthritis rats Thymus and Spleen index of the table 1 Myricaria bracteata effective site
Note: ###p < 0.001 compared with blank group, * p < 0.05.IR: suppression ratio compared with model group
The impact on adjuvant arthritis rats body weight of the table 2 Myricaria bracteata effective site
Note: * p < 0.05 compared with model group.
Myricaria bracteata effective site 20mg/kg can suppress adjuvant arthritis rats Secondary cases at administration 12d
Foot swelling, suppression ratio is 4.53% (P < 0.05) (Dex is 11.4% with time point suppression ratio), is being administered 15d
Adjuvant-induced arthritis thymus index can be suppressed, but index and spleen index is not affected.SBZ during being administered to greatly
Mus body weight does not has obvious inhibitory action.
Experimental example 3: Myricaria bracteata effective site (SBZ group) evaluation of effect arthritic to anti-rat collagen type
Laboratory animal: Wistar rat, male, 110-130g, SPF level, Military Medical Science Institute's laboratory animal
Center provides, quality certification SCXK (army) 2007-004.Laboratory animal is randomly divided into 5 groups by body weight, respectively
For blank group (11), model group (12), SBZ group (12) and Dex group (12).
Test medicine: SBZ component；Dexamethasone sodium phosphate injection (Dex), traditional Chinese medicines group holds raw pharmacy to be had
Limit company (traditional Chinese medicines quasi-word H41020036).
Experimental technique:
1. modeling preparation collagen emulsion, collagen is dissolved in the glacial acetic acid of 0.1M makes into 4mg/ml, and 4 DEG C overnight, add
The Freund's complete adjuvant entering equal volume carries out emulsifying, prepares the collagen emulsion of final concentration of 2mg/ml.Except blank
Outside group, every rat carries out initial immunity, 7d root of the tail at the left back sufficient sole of the foot intradermal injection collagen emulsion 0.1ml of 0d
Portion intradermal injection collagen emulsion 0.1ml carries out booster immunization.
2. observe rat hindlimb foot pawl arthroncus situation after packet is administered booster immunization, after obvious tumefaction occurs
It is grouped according to ankle joint girth stochastic averagina.Modeling 14d starts to be administered, successive administration 20d.
Medicine packet and administration: matched group (does not deals with), and model group (gives solvent), Dex (0.2mg/kg),
SBZ (200mg/kg), each administration group is oral administration.
3. the medicine therapeutical effect to arthritis
Every day observes the swelling of left and right hind foot, body weight change, hair color, feed and the mental status.
Cause the special chi of scorching 16d, 20d, 23d, 26d, 29d, 32d, 34d measure injection side and inject right
Side ankle joint girth, and press formula calculating Drug inhibition rate:
4. thymus index and spleen index measures: 34d puts to death all animals, takes thymus, spleen, weighs,
Calculating thymus index, index and spleen index, organ index is calculated as every 10g body weight corresponding internal organs mg number.
5. pathologic finding: at rat after death, often organizes and takes 4 at random and leave and take pathology sample.Take off injection side respectively
With injection offside rat ankle joint, formalin fixes, 5% nitric acid decalcification, paraffin embedding, section, and HE contaminates
Color, light microscopy checking ankle joint pathological changes situation, and mark.
Standards of grading:
1) periarticular soft tissues:
0 point: no abnormality seen；
1 point: local soft tissue mild inflammatory changes: periarticular local soft tissue edema, it is seen that neutral on a small quantity
Granulocyte, lymphocytic infiltration；
2 points: local soft tissue inflammatory changes substantially: the obvious edema of periarticular soft tissues, thin vessels is congested,
A large amount of neutrophilic granulocyte, lymphocytic infiltrations, partially visible inflammatory granulation tissue is formed；
3 points: local soft tissue inflammatory changes notable: the notable edema of periarticular soft tissues, thin vessels is congested,
A large amount of neutrophilic granulocyte, lymphocytic infiltrations, local inflammation granulation tissue hyperplasia, a large amount of granulomas and abscess shape
Become；
2) synovial tissue
0 point: no abnormality seen；
1 point: locally synovial tissue's mild inflammatory changes: periarticular synovial tissue Mild edema, synovial cell swells
Swollen, monolayer alignment, the most visible a small amount of neutrophilic granulocyte, lymphocytic infiltration；
2 points: locally synovial tissue's inflammatory changes substantially: the obvious edema of periarticular synovial tissue, synovial cell swells
Swollen, hypertrophy substantially, arrange in multilamellar, is dispersed in neutrophilic granulocyte and lymphocytic infiltration around synovial tissue；
3 points: locally synovial tissue's inflammatory changes notable: the notable hypertrophy of periarticular synovial tissue, inflammatory reaction shows
Write, a large amount of neutrophilic granulocyte, lymphocytic infiltrations, blood capillary proliferation, partially visible inflammatory meat around synovial membrane
Bud is swollen to be formed；
3) cartilage
0 point: no abnormality seen；
1 point: articular surface cartilaginous tissue is the most impaired, it is seen that in cartilage, pannus is formed, and articular surface is the most complete；
2 points: articular cartilage damage is obvious, locally defect seen from articular surface cartilage, defect inflammatory fibrous tissue
Hypertrophy, neutrophilic granulocyte, lymphocytic infiltration；
3 points: inflammation accumulates whole articular cavity, articular cartilage damage is notable, articular surface cartilage serious defect, defect
Position by inflammatory fibrous tissue substitute, local a large amount of neutrophilic granulocyte, lymphocytic infiltrations；
4) osseous tissue, medullary cavity
0 point: no abnormality seen；
1 point: partially visible indivedual bone trabecula rupture, medullary cavity merges, and inflammatory reaction occurs in having no medullary cavity；
2 points: osseous tissue is impaired substantially, impaired place inflammatory fibrous hamartoplasia, a large amount of neutrophilic granulocytes, lymph are thin
Born of the same parents infiltrate, and substantially, medullary cavity merges the fracture of local bone girder, neutrophil infiltration seen from medullary cavity (or
Bone marrow cell proliferation enlivens), but inflammatory tissue hypertrophy in having no medullary cavity；
3 points: osseous tissue is corroded serious by inflammatory tissue, and inflammation involves medullary cavity, a large amount of in partially visible medullary cavity
Inflammatory fibrous hamartoplasia, bone marrow is substituted by being organized as inflammatory fibrous tissue；
5) total score
Owing to presenting inflammatory performance from periarticular soft tissues, the course of disease is delayed, synovial tissue, cartilage, osseous tissue
Presenting inflammatory reaction with medullary cavity is the process that a course of disease gradually increases the weight of, to each sample in aforementioned four side
(periarticular tissue weighted number is 1, synovial membrane group to use weighted mean when the pathological manifestations in face carries out Comprehensive Assessment
Knitting weighted number is 2, and cartilage weighted number is 3, and osseous tissue and medullary cavity weighted number are 4).
Experimental result: model group relatively matched group obvious tumefaction, display modeling success；Animal foot pawl swelling after modeling,
Inconvenient activity, hair color, the mental status and feed are without significant change, dexamethasone treated animal relatively model group and comparison
Group mental alertness, SBZ group relatively model group has no significant change；
1) each experimental group body weight change situation.
After modeling, animal relatively matched group is put on weight to differ from swelling degree and is strengthened, positive control drug dexamethasone (Dex)
Compared with model group, body weight is remarkably decreased, and body weight is had no significant effect (see Fig. 5) by SBZ；As it is shown in figure 5,
After administration, model group is compared with matched group, and body weight difference increases the weight of to increase with swelling degree, and after modeling, the weight of animals increases
Length slows down, and except walking disorder, model group feed, hair color, the mental status are without significant change；DEX can significantly drop
Low the weight of animals, and spirit is vigorous；After SBZ is administered, the weight of animals, without significant change, is prompted to pharmaceutical quantities and exists
Without obvious toxic-side effects during administration.
2) medicine impact on collagen-induced arthritis in rats foot pawl swelling.
After modeling, positive control drug Dex significantly inhibits collagen type rats with arthritis injection side and offside swelling
(p < 0.001), SBZ group has no obvious inhibiting effect (be shown in Table 3 and table 4) to foot pawl swelling；After causing scorching 14d,
Animal hind leg injection side and offside obvious tumefaction (p < 0.001), Dex is administered 2d and i.e. shows significant difference, extremely
Be administered 20d injection side and offside inhibitory rate of intumesce are respectively 26.3%, 11.4%, SBZ to foot pawl swelling without bright
Aobvious inhibitory action.
The effect (injection side) to collagen-induced arthritis in rats left hind swelling of the table 3 Myricaria bracteata effective site
1.#p < 0.05, ##p < 0.01, ###p < 0.001 compares with matched group；* P < 0.05, * * P < 0.01, * * * P < 0.001,
Compare with model group；
2. after administration group Articular swelling, numerical value is ankle swelling suppression ratio (%).
The effect (injection offside) to collagen-induced arthritis in rats right hind swelling of the table 4 Myricaria bracteata effective site
1.#p < 0.05, ##p < 0.01, ###p < 0.001 compares with matched group；* P < 0.05, * * P < 0.01, * * * P < 0.001, with
Model group compares；
2. after administration group Articular swelling, numerical value is ankle swelling suppression ratio (%).
3) medicine is on spleen, the impact of thymus index
After modeling, index and spleen index significantly raises (p < 0.001), and Dex significantly reduces index and spleen index (p < 0.001),
SBZ group index and spleen index is in a slight decrease, but there was no significant difference；After modeling, thymus index is in a slight decrease, without aobvious
Writing sex differernce, Dex significantly reduces index and spleen index (p < 0.001), SBZ group thymus index reduction (p < 0.05) (see
Table 5).
Table 5 Myricaria bracteata effective site is on collagen-induced arthritis in rats spleen, the impact of thymus index
* organ index is calculated as every 10g body weight corresponding internal organs mg number；Model group compares p value with matched group, each administration group with
Model group compares, analytical statistics difference.
Spleen and thymus are main immune organs, play important regulation effect in inflammatory reaction.Modeling
Rear index and spleen index significantly raises (p < 0.001), and thymus index is in a slight decrease, there was no significant difference, prompting immunity
System activation, participates in inflammatory reaction；DEX significantly reduces Thymus and spleen index (p < 0.001), has bright
Aobvious immunoregulatory activity；After giving SBZ, index and spleen index is in a slight decrease, but there was no significant difference, and thymus refers to
Number reduces, and wherein SBZ group has significant difference (p < 0.05), prompting medicine may have certain immunomodulating
Activity, but effect is the strongest.
4. the medicine impact on collagen induced arthritis ankle joint pathological score
Model group is compared with matched group, and pathological score significantly raises (p < 0.001), and Dex significantly reduces injection side and offside
Pathological score (p < 0.05)；SBZ significantly reduces injection side pathological score (p < 0.05), but comments the pathology of offside
Point unknown significance impact (be shown in Table 6 and table 7).
Table 6 medicine is to collagen-induced arthritis in rats ankle joint effect pathological score table (injection side)
1.#p < 0.05, ##p < 0.01, ###p < 0.001 compares with matched group；* P < 0.05, * * P < 0.01, * * * P < 0.001, with
Model group compares；
2. after administration group Articular swelling, numerical value is suppression ratio (%) corresponding compared with model group.
Table 7 medicine is to collagen-induced arthritis in rats ankle joint effect pathological score table (injection offside)
1.#p < 0.05, ##p < 0.01, ###p < 0.001 compares with matched group；* P < 0.05, * * P < 0.01, * * * P < 0.001, with
Model group compares；
2. after administration group Articular swelling, numerical value is suppression ratio (%) corresponding compared with model group.
Model group is compared with matched group, and injection side and offside pathological score significantly raise (p < 0.001), periarticular
Tissue, synovial tissue's hypertrophy, cartilage destruction, osseous tissue and medullary cavity are destroyed the most serious；DEX significantly presses down
Inflammatory destruction processed, total score suppression ratio is respectively injection side 46.6% (p < 0.001), offside 46.8% (p < 0.01)；
Injection side cartilage, osseous tissue and medullary cavity are destroyed and are shown certain inhibitory action by SBZ, comment offside pathology
Point without obvious inhibiting effect, total score suppression ratio be respectively 21.4% (p < 0.05), 8.8%.
Conclusion: result above shows, collagen induced arthritis rat foot claw swelling is suppressed by Myricaria bracteata effective site
Activity has no notable significant difference；To some key index, such as index and spleen index, thymus index, ankle joint is sick
Reason grade form reveals certain inhibitory action, and display compound is to alleviating and suppression rheumatoid arthritis local inflammation
Progress, there is potential regulation inhibitory activity, prevent and treat the purposes in rheumatism, rheumatoid arthritis.
Claims (11)
1. the preparation method of Cacumen Myricariae Germanicae effective site, it is characterised in that include below step:
(1) by Cacumen Myricariae Germanicae Myricaria germanica L.Desv and the twig of congener, suitably pulverize, then
By solvent percolation, extraction or heating and refluxing extraction, extracting solution normal pressure or concentrating under reduced pressure obtain extractum；
(2) the separated method of this extractum refines, purification obtains Cacumen Myricariae Germanicae effective site.
Preparation method the most according to claim 1, it is characterised in that the Cacumen Myricariae Germanicae described in step (1) and with
Platymiscium is Myricaria bracteata, Cacumen Myricariae Germanicae.
Preparation method the most according to claim 1, it is characterised in that the Extraction solvent described in step (1) be water,
Alcohols, acetone or water and alcohols or the mixed solvent of acetone；Wherein said alcohols includes: methanol, ethanol,
The mixed solvent of one or more in propanol or butanol.
Preparation method the most according to claim 1, it is characterised in that the separation method described in step (2) is extraction
Rear chromatography；Wherein said chromatography method includes that macroporous adsorption resin chromatography, MCI resin chromatography, glucosan are solidifying
Glue Sephadex LH-20 chromatography, Toyoperal gel chromatography or reversed-phase silica gel chromatography or above-mentioned chromatography method
Combination.
Preparation method the most according to claim 4, it is characterised in that the solvent that described extraction is used be petroleum ether,
Toluene, ether, chloroform, dichloromethane, ethyl acetate, n-butyl alcohol, isopropanol, acetone, ethanol,
One or several mixed solvents in methanol, water；The described solvent used by chromatography is petroleum ether, toluene, second
Ether, chloroform, dichloromethane, ethyl acetate, n-butyl alcohol, isopropanol, acetone, ethanol, methanol, water
In one or several mixed solvents.
Preparation method the most according to claim 5, it is characterised in that mixed selected from water and ethanol of described mixed solvent
Bonding solvent, wherein the percentage ratio of ethanol is 30%-50%.
7. a Cacumen Myricariae Germanicae effective site, it is characterised in that described effective site is according to arbitrary in claim 2-6
Described preparation method prepares.
Cacumen Myricariae Germanicae effective site the most according to claim 7, it is characterised in that the effective ingredient of described effective site
It it is hydrolysable tannin compounds.
9. a pharmaceutical composition, it is characterised in that the effective portion of Cacumen Myricariae Germanicae of claim 7-8 containing effective dose
Position and pharmaceutically acceptable carrier.
10. according to the pharmaceutical composition in claim 9, it is characterised in that described pharmaceutical composition include injection,
Tablet, capsule, pill, oral liquid, patch, decoction, granule or drops.
The arbitrary described Cacumen Myricariae Germanicae effective site of 11. claim 7-8 or the arbitrary described drug regimen of claim 9-10
Thing purposes in preparation prevention and/or treatment rheumatism, medicine for treating rheumatoid arthritis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015102083249 | 2015-04-23 | ||
| CN201510208324 | 2015-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106063802A true CN106063802A (en) | 2016-11-02 |
Family
ID=57420700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610262319.0A Pending CN106063802A (en) | 2015-04-23 | 2016-04-25 | Cacumen Myricariae Germanicae effective site, Its Preparation Method And Use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106063802A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114699439A (en) * | 2022-04-01 | 2022-07-05 | 江南大学 | Five-flavor manna spontaneous heating gel patch with anti-inflammatory effect and preparation method thereof |
-
2016
- 2016-04-25 CN CN201610262319.0A patent/CN106063802A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| JIA-BAO LIU等: "Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata", 《JOURNAL OF NATURAL PRODUCTS ARTICLE》 * |
| 周嵘等: "宽苞水柏枝化学成分研究", 《中国中药杂志》 * |
| 张瑛: "宽苞水柏枝抑制HIV_1复制有效成分及其构效关系的研究", 《中国优秀硕士学位论文全文数据库》 * |
| 黄元: "藏药翁布化学成分的研究及抗RA有效部位的筛选", 《中国优秀硕士学位论文全文数据库》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114699439A (en) * | 2022-04-01 | 2022-07-05 | 江南大学 | Five-flavor manna spontaneous heating gel patch with anti-inflammatory effect and preparation method thereof |
| CN114699439B (en) * | 2022-04-01 | 2023-08-08 | 江南大学 | Five-flavor mannose self-heating gel patch with anti-inflammatory effect and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003260985B2 (en) | Extraction and purification method of active constituents from stem of Lonicera japonica Thunb., its usage for anti-inflammatory and analgesic drug | |
| WO2018058261A1 (en) | Traditional chinese medicine composition for treating psoriasis and preparation method thereof | |
| CN101612362B (en) | Complex preparation for regulating lipid and preventing and curing heart cerebrovascular diseases and preparation method thereof | |
| CN102302555A (en) | Chinese medicinal extract for treating urarthritis, as well as preparation method and application thereof | |
| US8945633B2 (en) | Pharmaceutical composition for preventing and treating inflammatory diseases containing an ethyl acetate fraction of dried extract of Trachelospermi caulis as an active ingredient, and method for producing the fraction | |
| Li et al. | Fengshi Qutong capsule ameliorates bone destruction of experimental rheumatoid arthritis by inhibiting osteoclastogenesis | |
| CN105055462A (en) | Traditional Chinese medicine extract for preventing and treating AD (Alzheimer's disease) and application of extract | |
| Li et al. | Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress | |
| Dewi et al. | A comprehensive review on the phytoconstituents and biological activities of Nyctanthes arbor-tristis L. | |
| CN106421075A (en) | Preparation method and application of anti-oxidation active component of bamboo willows | |
| CN104510853A (en) | Traditional Chinese medicinal effective part composition for treating dysmenorrhea of women and application of traditional Chinese medicinal effective part composition | |
| CN106063802A (en) | Cacumen Myricariae Germanicae effective site, Its Preparation Method And Use | |
| CN104435977B (en) | It is a kind of to be used to treat medicine of hepatic injury and preparation method thereof | |
| CN102228666B (en) | Composition prepared from pine pollen and curcuma, preparation method thereof, and application of composition in preparing medicament for treating inflammatory bowel disease | |
| CN1771978A (en) | Notoginseng triol-saponin composition and its prepn and use | |
| CN113350390A (en) | Total sesquiterpene lactone of saussurea involucrata, preparation method and pharmaceutical application thereof | |
| CN101439069B (en) | Leaf extract of Herba siegesbeckiae, preparation method and uses thereof | |
| CN1969963A (en) | Method for extracting medicament effective component for treating hepatitis and medicinal composition thereof | |
| CN104435293B (en) | Application of the Kadsura heteroclita total triterpene ethanol extract in preparation anti-arthritic drugs | |
| CN103933386B (en) | Compound hemophiliac capsule used for treating hemophilia and preparation method thereof | |
| CN112089738A (en) | Preparation method and application of caulis sinomenii extract | |
| CN102670865A (en) | Process for extracting active ingredients of American eleutherine rhizome | |
| CN1981832A (en) | Use of cape-jasmine extract in treatment of chronic hepatitis B | |
| CN103110700A (en) | Fraxinus mandshurica extract for treating rheumatoid arthritis | |
| CN100486600C (en) | Application of spanishneedles herb flavonid in preparing medicine for preventing and treating liver fibrosis |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161102 |