CN112972641B - 一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 - Google Patents
一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN112972641B CN112972641B CN202110174580.6A CN202110174580A CN112972641B CN 112972641 B CN112972641 B CN 112972641B CN 202110174580 A CN202110174580 A CN 202110174580A CN 112972641 B CN112972641 B CN 112972641B
- Authority
- CN
- China
- Prior art keywords
- parts
- chinese medicine
- traditional chinese
- pain
- medicine composition
- 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.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 73
- 239000000203 mixture Substances 0.000 title claims abstract description 47
- 208000037819 metastatic cancer Diseases 0.000 title claims abstract description 31
- 208000011575 metastatic malignant neoplasm Diseases 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 52
- 208000001294 Nociceptive Pain Diseases 0.000 claims abstract description 17
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 235000003255 Carthamus tinctorius Nutrition 0.000 claims abstract description 9
- 244000020518 Carthamus tinctorius Species 0.000 claims abstract description 9
- 241000218176 Corydalis Species 0.000 claims abstract description 9
- 239000009636 Huang Qi Substances 0.000 claims abstract description 9
- 241000766380 Iphigenia Species 0.000 claims abstract description 9
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 9
- 235000008397 ginger Nutrition 0.000 claims abstract description 9
- 244000223760 Cinnamomum zeylanicum Species 0.000 claims abstract description 8
- 241000007126 Codonopsis pilosula Species 0.000 claims abstract description 8
- 235000017803 cinnamon Nutrition 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 9
- 230000001394 metastastic effect Effects 0.000 claims description 9
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 241000234314 Zingiber Species 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 235000013399 edible fruits Nutrition 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 3
- 206010006002 Bone pain Diseases 0.000 claims description 3
- 244000241463 Cullen corylifolium Species 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 230000000392 somatic effect Effects 0.000 claims 1
- 208000002193 Pain Diseases 0.000 abstract description 38
- 206010027476 Metastases Diseases 0.000 abstract description 32
- 230000009401 metastasis Effects 0.000 abstract description 31
- 230000000694 effects Effects 0.000 abstract description 26
- 201000011510 cancer Diseases 0.000 abstract description 21
- 206010028980 Neoplasm Diseases 0.000 abstract description 19
- 208000024891 symptom Diseases 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 5
- 230000001976 improved effect Effects 0.000 abstract description 5
- 230000003213 activating effect Effects 0.000 abstract description 4
- 230000017531 blood circulation Effects 0.000 abstract description 4
- 238000010792 warming Methods 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 2
- 244000273928 Zingiber officinale Species 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 23
- 210000003141 lower extremity Anatomy 0.000 description 14
- 230000019491 signal transduction Effects 0.000 description 14
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 12
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 206010058019 Cancer Pain Diseases 0.000 description 8
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 8
- 108010057466 NF-kappa B Proteins 0.000 description 7
- 102000003945 NF-kappa B Human genes 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 102000003390 tumor necrosis factor Human genes 0.000 description 7
- 206010030113 Oedema Diseases 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 5
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 5
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 5
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 5
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000031018 biological processes and functions Effects 0.000 description 5
- 230000004879 molecular function Effects 0.000 description 5
- 231100000862 numbness Toxicity 0.000 description 5
- 210000002997 osteoclast Anatomy 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 235000005875 quercetin Nutrition 0.000 description 5
- 229960001285 quercetin Drugs 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 4
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 4
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 4
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229940076810 beta sitosterol Drugs 0.000 description 4
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000010201 enrichment analysis Methods 0.000 description 4
- 210000001624 hip Anatomy 0.000 description 4
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 4
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 4
- 235000009498 luteolin Nutrition 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 4
- 229950005143 sitosterol Drugs 0.000 description 4
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 4
- 229940032091 stigmasterol Drugs 0.000 description 4
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 4
- 235000016831 stigmasterol Nutrition 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- FXNFHKRTJBSTCS-UHFFFAOYSA-N Baicalein Natural products C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 description 3
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 3
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 3
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 3
- 208000006083 Hypokinesia Diseases 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 102100026236 Interleukin-8 Human genes 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 108091054455 MAP kinase family Proteins 0.000 description 3
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 108091008611 Protein Kinase B Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 208000022531 anorexia Diseases 0.000 description 3
- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 description 3
- 229940015301 baicalein Drugs 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 206010061428 decreased appetite Diseases 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 235000008777 kaempferol Nutrition 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000027939 micturition Effects 0.000 description 3
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000006916 protein interaction Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 102100027211 Albumin Human genes 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102000003952 Caspase 3 Human genes 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 101000693913 Homo sapiens Albumin Proteins 0.000 description 2
- 101001065295 Homo sapiens Fas-binding factor 1 Proteins 0.000 description 2
- 101000603877 Homo sapiens Nuclear receptor subfamily 1 group I member 2 Proteins 0.000 description 2
- 101001098560 Homo sapiens Proteinase-activated receptor 2 Proteins 0.000 description 2
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 2
- 101000713170 Homo sapiens Solute carrier family 52, riboflavin transporter, member 1 Proteins 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 2
- 206010049816 Muscle tightness Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102000008108 Osteoprotegerin Human genes 0.000 description 2
- 108010035042 Osteoprotegerin Proteins 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 206010033372 Pain and discomfort Diseases 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 2
- 102000009572 RNA Polymerase II Human genes 0.000 description 2
- 108010009460 RNA Polymerase II Proteins 0.000 description 2
- 102000010498 Receptor Activator of Nuclear Factor-kappa B Human genes 0.000 description 2
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 description 2
- 102000003566 TRPV1 Human genes 0.000 description 2
- 101150016206 Trpv1 gene Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 2
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 2
- 210000001361 achilles tendon Anatomy 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 210000001099 axilla Anatomy 0.000 description 2
- 229960000997 bicalutamide Drugs 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 238000013332 literature search Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000003334 potential effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 108091006084 receptor activators Proteins 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 229940126680 traditional chinese medicines Drugs 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010006312 Breast swelling Diseases 0.000 description 1
- PMTBZAVERRPRHU-YGVNLFKFSA-N CC1(C)CCCC(C)=C1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C.CC1(C)CCCC(C)=C1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C Chemical compound CC1(C)CCCC(C)=C1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C.CC1(C)CCCC(C)=C1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C PMTBZAVERRPRHU-YGVNLFKFSA-N 0.000 description 1
- 235000008499 Canella winterana Nutrition 0.000 description 1
- 244000080208 Canella winterana Species 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 241000756943 Codonopsis Species 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 108700039964 Duplicate Genes Proteins 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 101001052490 Homo sapiens Mitogen-activated protein kinase 3 Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 102000001284 I-kappa-B kinase Human genes 0.000 description 1
- 108060006678 I-kappa-B kinase Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000015617 Janus Kinases Human genes 0.000 description 1
- 108010024121 Janus Kinases Proteins 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 108010070503 PAR-2 Receptor Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010034156 Pathological fracture Diseases 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 1
- 102000018402 Protease-activated receptor 2 Human genes 0.000 description 1
- 102000002020 Protease-activated receptors Human genes 0.000 description 1
- 108050009310 Protease-activated receptors Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241001446509 Psoralea Species 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 101710203837 Replication-associated protein Proteins 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000005250 Spontaneous Fractures Diseases 0.000 description 1
- 108010062740 TRPV Cation Channels Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 230000010632 Transcription Factor Activity Effects 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 1
- 229960000853 abiraterone Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 229940017545 cinnamon bark Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000011382 collagen catabolic process Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000000010 osteolytic effect Effects 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 238000003068 pathway analysis Methods 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000020167 protein autophosphorylation Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000013185 thoracic computed tomography Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 201000007423 tubular adenocarcinoma Diseases 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Images
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)
- A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/286—Carthamus (distaff thistle)
-
- 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)
- A61K36/34—Campanulaceae (Bellflower family)
- A61K36/344—Codonopsis
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/487—Psoralea
-
- 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)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
-
- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用，所述中药组合物包含如下质量份的原料药：延胡索10‑30份、红花5‑15份、补骨脂10‑30份、山慈菇10‑30份、炙黄芪15‑45份、干姜6‑12份、党参15‑45份、肉桂5‑15份。本发明针对骨转移癌性躯体痛，以温阳活血止痛为治则，经多年临床经验及药理学研究明确，可明显改善骨转移癌性躯体痛的临床症状，具有疗效确切、无毒副作用、成本低廉、便于应用的优势。
Description
技术领域
本发明涉及中医药技术领域，特别是涉及一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用。
背景技术
癌痛是一种主观感觉，定义为“与实际或潜在的组织损伤或者类似损伤相关联的感觉和情绪体验”，是肿瘤患者最常见、最难以忍受的症状之一，极大地影响着患者的日常活动、自理能力、情感活动，甚至影响患者与他人之间的关系。如果癌症疼痛不能得到及时、有效的控制，患者往往感到极度不适，可能会引起或加重其食欲减退、焦虑、乏力、失眠等症状，甚至情绪消沉以致患上抑郁症，显著影响患者的日常活动、自理能力、工作、社会交往和整体生活质量。据统计，53％癌症患者经历过疼痛，25％新诊断患者有疼痛，59％正在接受治疗的患者发生疼痛，其中1/3的患者为重度疼痛，33％癌症治愈患者存在与癌症或治疗相关的慢性疼痛，而晚期癌症患者的疼痛发生率可达60％-80％。
癌性疼痛可进一步分为躯体痛和内脏痛，躯体痛通常能相对定位准确，主诉为刀割样、搏动性和压迫样疼痛，多由恶性肿瘤骨转移引起。骨转移引起的疼痛是癌性躯体痛的最主要原因，骨骼是晚期恶性肿瘤最常见的转移和受累部位，是继肝脏、肺部之后第3个易发生肿瘤转移的器官，晚期恶性肿瘤2/3合并有骨转移，骨转移可引起骨质破坏，表现为骨痛、病理性骨折和高钙血症等，是对患者最直接、最明显的影响，导致了患者活动受限及生活质量显著降低。据统计，约有80％骨转移患者癌性疼痛不能得到有效控制，骨转移患者如果尚未发生严重的内脏器官转移，还可有相对较长的生存时间，合理治疗具有重大意义。西医缓解骨转移癌痛的方法有很多，包括：镇痛药、放射治疗、二膦酸盐、手术、免疫、靶向、生物等治疗，但其存在治疗瓶颈，且大多数骨转移癌患者本身体力较弱，难以耐受放化疗所带来的副作用，而且大多数恶性肿瘤骨转移发现时已处于晚期，预后差，大多无法达到治愈的要求，因此，缓解骨疼痛、改善生活质量是目前恶性肿瘤骨转移治疗中最主要的目标。
近年来中医药以其副作用少、疗效佳等优势在骨转移癌治疗中取得了较好的临床效果，受到了临床医生的广泛关注。中医学认为，骨转移癌痛是因瘤毒邪气阻滞经络气血致机体某部位发生疼痛，属“骨瘤”、“骨疽”、“骨痹”等范畴。《素问举痛论举痛论第三十九》云：“寒气客于脉外，则脉寒，脉寒则缩蜷，缩蜷则脉绌急，则外引小络，故卒然而痛。得炅则痛立止，因重中于寒，则痛久矣”。中医学认为癌性躯体痛的病机不外“不通则痛”、“不荣则痛”，其中寒主收引，阴寒凝滞，血脉闭塞，经络不通，不通则痛是癌性疼痛的主要病机之一。中医疗法副作用小，在镇痛的同时能够帮助解决精神、心理对患者疼痛所造成的影响，改善患者的主观症状，提高患者的生活质量。与止痛药配合使用，可增强止痛药的疗效，减少其用量，减轻其副作用，是癌性疼痛综合治疗中的有效方法，被广泛接受。
发明内容
基于此，有必要针对目前西医缓解骨转移癌痛存在的副作用较大等问题，提供一种治疗骨转移癌性躯体痛的中药组合物及其应用。
一种治疗骨转移癌性躯体痛的中药组合物，所述中药组合物包含如下质量份的原料药：延胡索10-30份、红花5-15份、补骨脂10-30份、山慈菇10-30 份、炙黄芪15-45份、干姜6-12份、党参15-45份、肉桂5-15份。
在其中一个实施例中，所述中药组合物由如下质量份的原料药组成：延胡索20份、红花10份、补骨脂20份、山慈菇20份、炙黄芪30份、干姜9份、党参30份、肉桂10份。
本发明还提供了上述治疗骨转移癌性躯体痛的中药组合物的制备方法，包括如下步骤：
(1)按照质量份称取原料药，加入5-10倍质量份的水浸泡30-120分钟；
(2)将浸泡后的原料药连水一同加热煎煮，过滤，收集滤液；
(3)将滤渣重新加入5-10倍质量份的水，煎煮，过滤，收集滤液；
(4)将两次煎煮后过滤得到的滤液合并，加热浓缩，即得汤剂。
在其中一个实施例中，两次煎煮的时间均为30-60分钟。
在其中一个实施例中，滤液合并后加热浓缩至原体积的10％-20％。
此外，本发明还提供了所述的治疗骨转移癌性躯体痛的中药组合物在制备治疗骨转移癌性躯体痛的药物中的应用。
本发明治疗骨转移癌性躯体痛的中药组合物方解如下：
补骨脂补肾助阳，红花活血通经、散瘀止痛为君药；干姜，温中散寒，辅以温阳，延胡索活血行气止痛，山慈菇消肿散结，为臣药；炙黄芪补气以助活血，党参健脾益肺，养血生津以佐制君臣之药攻伐燥热太过，为佐药；肉桂补火助阳，温通经脉，散寒止痛，引火归元以入肾经，为使药。全方共济温阳活血，通络止痛之效。
通过筛选本发明治疗骨转移癌性躯体痛的中药组合物的主要有效成分并构建成分与作用靶点互作网络，根据主要活性成分的关联度，明确中药组合物中的核心化合物主要有槲皮素(Quercetin)、豆甾醇(Stigmasterol)、木犀草素 (Luteolin)、β-谷甾醇(Beta-sitosterol)、山奈酚(Kaempferol)、黄芩素(Baicalein)、β-胡萝卜素(Beta-carotene)等，大部分化合物均具有抗肿瘤、抗炎和调节免疫的作用。其中槲皮素作为关键化合物，一方面可以通过抑制核因子κB受体活化因子配体(Receptor activator of NF-κB ligand，RANK-L)，核因子κB受体活化因子(receptor activator of NF-κB，RANK)等蛋白以及白介素(IL)-8，肿瘤坏死因子(tumor necrosis factor，TNF)-α等炎症介质的表达，增加骨保护素(Osteoprotegerin，OPG)的水平，进一步降低蛋白酶激活受体2/辣椒素受体1 (Proteinaseactivated receptors 2/Capsaicin receptor 1，PAR2/TRPV1)通路中的相关分子(如PAR2，TRPV1等)和TNF-α和IL-1β的水平，以抑制破骨细胞活化并减少骨破坏。豆甾醇和β-谷甾醇均可抑制脂多糖诱导的巨噬细胞产生和分泌多种炎症介质，如活性氧，一氧化氮和TNF-α，主要涉及到NF-κB信号通路：其中TNF-α可通过对核因子κB(Nuclear factor kappa-B，NF-κB)激酶β (IKKβ)的抑制功能来增加NF-κB，而NF-κB3抑制剂的泛素化可减少NF-κB。木犀草素可通过抑制PCNA蛋白和基质金属蛋白酶(Matrix metalloprotein， MMP)-9蛋白的表达及磷脂酰肌醇3激酶/蛋白激酶B(Phosphatidylinositol 3kinase/Protein kinaseB，PI3K/AKT)通路活化来阻碍癌细胞的增殖和迁移。同时，通过Cytoscape3.6.0软件构建本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的蛋白互作网络，发现其关键靶点为VEGFA、AKT1、IL6、 TP53、ALB、CXCL8、CASP3、TNF、EGFR、EGF和MAPK3。VEGFA具有调节血管生成和促进癌细胞增殖的作用，其通路受到缺氧诱导因子(Hypoxia induciblefactor，HIF)和Janus激酶/信号转导与转录激活子(The Janus kinase/signaltransducer and activator of tran-ions，JAK/STAT)通路的调节，且 VEGFA信号级联与MAPK通路有关。促骨因子IL-6和TNF-α都可以刺激成骨细胞产生RANKL，与破骨细胞前体表面的受体RANK结合，刺激下游信号分子，包括丝裂原活化蛋白激酶(Mitogen-activatedprotein kinase，MAPK)和 PI3K/AKT，并促进破骨细胞前体转化为功能性破骨细胞。CXCL8，也称为IL-8，通过与趋化因子受体(C-X-C chemokine receptor，CXCR)-1和CXCR2作用起调节炎症反应的作用。因此，本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的作用机制主要包含抗肿瘤，调节骨微环境与肿瘤细胞的相互作用等方面。当骨微环境缺氧时，HIF-1可启动缺氧基因的转录，这些基因对血管生成、肿瘤细胞凋亡和生长因子/细胞因子活性至关重要。此外，HIF-1 还可与生长因子/细胞因子(如VEGF，EGF等)相互作用，这些因子在癌细胞上的表达可进一步促进癌细胞的增殖和转移。
本发明与现有技术相比具有如下优点：
本发明中药药物组合物所用原料价廉，制备简便，使用方便，经多年临床应用和药理研究，对缓解骨转移所引起的疼痛、麻木、肢体活动不利，具有较好的疗效。鉴于骨转移癌性躯体痛发病人数较多，临床目前单纯止痛效果欠佳，本发明提供的中药复方制剂具有良好的应用前景。
本发明的中药组合物含有核心化合物槲皮素、豆甾醇、木犀草素、β-谷甾醇、山奈酚、黄芩素和β-胡萝卜素等，通过HIF-1、TNF、VEGF等信号通路对VEGFA、 IL6、TNF等靶点进行调控，具有抗癌、抑制骨转移和调节免疫的作用，作用机理明确。
附图说明
图1为本发明实施例中药组合物潜在治疗靶点核心基因示意图；
图2为本发明实施例中药组合物治疗骨转移癌性躯体痛的潜在治疗靶点和骨转移癌疾病靶点的韦恩图；
图3为本发明实施例中药组合物治疗骨转移癌性躯体痛的105个靶基因(A) 及核心基因(B)示意图；
图4为本发明实施例中药组合物治疗骨转移癌性躯体痛靶基因的GO功能富集分析图；
图5为本发明实施例中药组合物治疗骨转移癌性躯体痛靶基因的KEGG通路富集分析图。
具体实施方式
一种治疗骨转移癌性躯体痛的中药组合物，所述中药组合物包含如下质量份的原料药：延胡索10-30份、红花5-15份、补骨脂10-30份、山慈菇10-30 份、炙黄芪15-45份、干姜6-12份、党参15-45份、肉桂5-15份。
在其中一个较佳的实施例中：
所述中药组合物由如下质量份的原料药组成：延胡索20份、红花10份、补骨脂20份、山慈菇20份、炙黄芪30份、干姜9份、党参30份、肉桂10份。
上述治疗骨转移癌性躯体痛的中药组合物的制备方法，包括如下步骤：
(1)按照质量份称取原料药，加入原料药总质量5-10倍质量份的水浸泡 30-120分钟；
(2)将浸泡后的原料药连水一同加热煎煮，过滤，收集滤液；
(3)将滤渣重新加入原料药总质量5-10倍质量份的水，煎煮，过滤，收集滤液；
(4)将两次煎煮后过滤得到的滤液合并，加热浓缩，即得汤剂。
在其中一个较佳的实施例中，两次煎煮的时间均为30-60分钟。
在其中一个较佳的实施例中，滤液合并后加热浓缩至原体积的10％-20％。
所述的治疗骨转移癌性躯体痛的中药组合物可以应用于制备治疗骨转移癌性躯体痛的药物。
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施方式做详细的说明。在下面的描述中阐述了很多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似改进，因此本发明不受下面公开的具体实施例的限制。
实施例1
治疗骨转移癌性躯体痛的中药组合物有效成分的筛选
利用中药系统药理学数据库(TCMSP，http://lsp.Nwsuaf.edu.cn/tcmsp.php) 收集本发明的中药组合物8味中药的有效成分，筛选条件为口服生物利用度(oralbioavailability，OB)≥30％及类药性指数(drug-like index，DL)≥0.18；此外， TCMID(http://www.megabionet.org/tcmid/)和台湾中医药资源库(TCM Database@Taiwan，http://tcm.cmu.edu.tw/)作为补充数据库，并通过NCCN、中国知网等文献数据库检索药物的主要有效成分。
在TCMSP、TCMID和TCM Database@Taiwan数据库中检索到本发明治疗骨转移癌性躯体痛的中药组合物所有化学成分共计707个。以OB≥30％，DL≥0.18 为筛选标准，并结合文献检索，合计有效成分共109个：肉桂5个、干姜5个、红花22个、山慈菇3个、延胡索49个、党参21个、补骨脂3个、炙黄芪1个。如表1所示：
表1中药组合物的主要有效成分
实施例2
治疗骨转移癌性躯体痛的中药组合物药物有效成分作用靶点的预测
在TCMSP数据库中明确主要有效成分的靶蛋白，通过Uniprot数据库 (https://www.uniprot.org/)查询靶蛋白对应的基因名，并对靶蛋白进行标准化；文献检索获取的主要有效成分通过有机小分子生物活性数据库(PubChem， https://pubchem.ncbi.nlm.nih.gov/)获取典型SMILES结构，将SMILES结构导入Swiss TargetPrediction数据库(http://www.swisstargetprediction.ch/)预测潜在治疗靶点，选择物种为“Homo sapiens”，剔除重复内容后选择高概率目标，并利用 MCODE(Version 1.4.2，Bader Lab，University of Toronto)插件筛选核心基因。
通过TCMSP和Swiss Target Prediction数据库检索本发明治疗骨转移癌性躯体痛的中药组合物109个主要活性成分的潜在作用靶点，剔除重复内容后选择高概率目标，共得到374个潜在治疗靶点。通过STRING11.0数据库和 Cytoscape3.6.0软件将374个潜在治疗靶点的蛋白互作网络进行可视化，这个蛋白互作网络包含369个节点和7623条边。通过MCODE插件筛选出核心基因，明确核心基因有158个，分别属于3个子簇(得分≥10)，如图1A-C所示。子簇 A包含66个节点和1686条边；子簇B包含59个节点和426条边；子簇C由 33个节点和182条边组成。
实施例3
治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的主要潜在靶点分析
通过DisGeNet(http://www.disgenet.org/)和Drugbank(http://www.drugbank.ca/)网站寻找骨转移癌疾病相关基因，将搜索条件设置为“Gene”和“Homo sapien s”，删除重复基因并通过文献检索证明相关基因的正确性。
在DisGeNet和Drugbank数据库中以“Bone metastasis”为检索词，最终得到 773个靶基因，与药物374个潜在作用靶点进行映射(图2)，获得105个本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的靶点(图3A)。节点度越大说明该靶点越重要，根据节点度筛选出排名前25的关键靶点(图3 B)，其中节点度最高的11个基因如下：VEGFA(degree＝78)、AKT1(degree＝ 76)、IL6(degree＝76)、TP53(degree＝72)、ALB(degree＝72)、CXCL8(degr ee＝69)、CASP3(degree＝68)、TNF(degree＝66)、EGFR(degree＝66)、EGF(d egree＝66)、MAPK3(degree＝66)。
实施例4
治疗骨转移癌性躯体痛的中药组合物靶基因的功能分析
将本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的潜在靶点导入DAVID(https://david.ncifcrf.gov/)数据库，进行基因本体(Gene Ontology，GO)和基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析，其中GO分析依据功能的不同，可区分为生物过程(biological process，BP)、细胞成分(cellular component，CC)、分子功能(molecular function，MF)。
利用DAVID对105个本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的潜在靶点进行GO功能富集分析。在GO功能富集过程中共得到 143条结果，主要涉及BP(88项)、CC(11项)和MF(44项)。以错误发现率(false discovery rate，FDR)＜0.05为筛选条件，获得100个条目(BP63项， CC5项，MF32项)，筛选出涉及BP、MF的前10条富集结果，涉及CC的前5 条富集结果，如图4所示。在BP方面，包括RNA聚合酶II启动子转录的正调控、脂多糖介导的信号通路、转录的正调控，DNA模板化、5-羟色胺受体信号通路、磷脂酶C激活G蛋白偶联受体信号通路、细胞对血管内皮生长因子刺激的反应、胶原分解代谢过程\蛋白质自磷酸化、G蛋白偶联受体信号通路，与环核苷酸第二信使偶联、磷脂酰肌醇介导的信号传导等；在CC中，涉及树突、内溶酶体腔、血小板α颗粒腔、受体复合物、蛋白质细胞外基质等；在MF方面，涉及G蛋白偶联的5-羟色胺受体活性、血清素结合、神经递质受体活性、酶结合、丝氨酸型内肽酶活性、跨膜受体蛋白酪氨酸激酶活性、转录因子结合、蛋白酪氨酸激酶活性、蛋白激酶活性、RNA聚合酶II转录因子活性，配体激活的序列特异性DNA结合等。
对105个潜在治疗靶点进行KEGG通路分析，结果显示92条富集分析结果与本发明治疗骨转移癌性躯体痛的中药组合物治疗骨转移癌性躯体痛的作用机制相关，以FDR＜0.05作为富集筛选标准，得到84条符合此标准的通路，取排名前25的通路做富集功能分析(图5)。相关通路主要有HIF-1信号通路、TNF 信号通路、VEGF信号通路、ErbB信号通路、Toll样受体信号通路、Rap1信号通路等。
实施例5
治疗骨转移癌性躯体痛的中药组合物的实际临床应用
应用例1
刘XX，男，1942年5月出生，北京人。因“间断尿血2年余，下肢活动不利1周”以前列腺癌骨转移于2020年9月住院。2020年9月胸部CT提示脊椎(胸 T3-T12，肋骨):多椎体及附件广泛转移瘤。查体:疼痛评分7分，双侧下肢肌力3 级，肌张力4级，双下肢深感觉、浅感觉正常，双侧膝反射、跟腱反射存在。四诊合参，中医辨证为寒凝血瘀。在西医最基础对症治疗的基础上(比卡鲁胺、抑那通)，口服本发明中药组合物汤剂，定期检查，未见病情进展，目前患者活动自如，无不适主诉。目前查体:疼痛评分0分，双侧下肢肌力5级，肌张力5 级，双下肢深感觉、浅感觉正常，双侧膝反射、跟腱反射存在。出院后随访。目前患者病情持续好转，定期来院复查。
应用例2
柳XX，女，1944年12月出生，北京人。2009年11月自觉右乳胀痛不适，后行右侧乳腺单纯切除术，术后病理示：(右乳)小管癌。术后未行放、化疗，行5年来由唑内分泌治疗。后定期复查。2020年7月自觉右侧胸部、腋下胀痛不适，行ECT-全身骨显像检查提示骨转移。NRS评分：7分，KPS评分：60分。四诊合参，中医辨证为寒凝血瘀，予口服本发明中药组合物汤剂，连续7天，后NRS评分1分，KPS评分：90分。右侧胸部、腋下胀痛不适明显减轻，呼吸均匀，夜眠安。至2021年1月先后我科住院5次寻求中医调理，最后一次出院后随访病情稳定，偶尔右侧胸部、腋下胀痛(NRS评分1分)，余无特殊。
应用例3
曾XX，男，1944年2月出生，四川省巴中市人。2018年2月出现腰部隐痛不适，下肢疼痛、麻木，小便频，乏力等症状。为异地结算患者，先后19次在我科住院寻求中医调理。2018年5月17日前列腺增强MRI提示:前列腺癌；左侧腹股沟区淋巴结及骨盆多发转移瘤。ECT检查提示：全身骨多发浓聚区(枕骨、脊柱多节椎体、双侧多根肋骨，肩胛骨，骨盆)，考虑多发骨转移。NRS评分：7分，KPS评分：70分。2018年5月24日行前列腺穿刺活检示:(右上、左下、左中、左上)前列腺癌，Gleason评分9分。2018年5月开始行内分泌治疗(比卡鲁胺，抑那通)，并间断本发明中药复方制剂加减，后NRS降至2分， KPS升至80分。腰部隐痛不适明显改善，下肢疼痛、麻木基本消失，小便频减轻，乏力减轻。2019年3月肿标再次逐渐上升，开始行化疗，后因化疗相关乏力，拒绝进一步化疗，间断口服本复方制剂，腰部隐痛、下肢疼痛、麻木、小便频、乏力等症状未见加重。2019年10月开始行内分泌治疗(阿比特龙)至今，期间予口服本发明中药组合物汤剂，患者骨转移癌痛消失，乏力减轻，小便正常，无下肢疼痛、麻木。出院后随访病情稳定，目前NRS评分：0分，KPS评分：90分。
应用例4
尚XX，女，1952年3月出生，北京人。2019年9月出现间断腹胀痛，并伴腰背疼痛不适，2020年1月医科院肿瘤医院行PET-CT考虑：卵巢癌晚期；腹膜多发转移；多发淋巴结转移；骨转移(骶骨溶骨性骨转移)。后因疫情未行进一步诊疗。2020年6月出现双下肢浮肿，左侧重度非可凹性水肿，右下肢中度非可凹性水肿，并伴乏力，纳差。2020年8月18日因疼痛加重明显(NRS 评分8分)收入我科，给予本复方制剂加减口服，并予支持对症治疗，疼痛评分降至4分，双下肢浮肿减轻，乏力减轻，纳差好转。2020年11月2日行局部穿刺活检，2020年11月27日病理回报：卵巢腺癌，给予紫杉醇+卡铂化疗2周期，并予口服本发明中药组合物汤剂，患者经中西医结合治疗，症状得到很好改善，2021-1-19患者间断腹胀痛、腰背痛减轻(NRS评分2分)，右下肢无浮肿，左下肢轻度浮肿，乏力好转，纳可。CT示病情稳定。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (6)
1.一种治疗骨转移癌性躯体痛的中药组合物，其特征在于，所述中药组合物由如下质量份的原料药组成：延胡索10-30份、红花5-15份、补骨脂10-30份、山慈菇10-30份、炙黄芪15-45份、干姜6-12份、党参15-45份、肉桂5-15份。
2.根据权利要求1所述的治疗骨转移癌性躯体痛的中药组合物，其特征在于，所述中药组合物由如下质量份的原料药组成：延胡索20份、红花10份、补骨脂20份、山慈菇20份、炙黄芪30份、干姜9份、党参30份、肉桂10份。
3.如权利要求1-2任一项所述的治疗骨转移癌性躯体痛的中药组合物的制备方法，其特征在于，包括如下步骤：
(1)按照质量份称取原料药，加入5-10倍质量份的水浸泡30-120分钟；
(2)将浸泡后的原料药连水一同加热煎煮，过滤，收集滤液；
(3)将滤渣重新加入5-10倍质量份的水，煎煮，过滤，收集滤液；
(4)将两次煎煮后过滤得到的滤液合并，加热浓缩，即得汤剂。
4.根据权利要求3所述的治疗骨转移癌性躯体痛的中药组合物的制备方法，其特征在于，两次煎煮的时间均为30-60分钟。
5.根据权利要求3所述的治疗骨转移癌性躯体痛的中药组合物的制备方法，其特征在于，滤液合并后加热浓缩至原体积的10％-20％。
6.如权利要求1-2任一项所述的治疗骨转移癌性躯体痛的中药组合物在制备治疗骨转移癌性躯体痛的药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110174580.6A CN112972641B (zh) | 2021-02-07 | 2021-02-07 | 一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110174580.6A CN112972641B (zh) | 2021-02-07 | 2021-02-07 | 一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112972641A CN112972641A (zh) | 2021-06-18 |
| CN112972641B true CN112972641B (zh) | 2022-03-22 |
Family
ID=76347816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110174580.6A Active CN112972641B (zh) | 2021-02-07 | 2021-02-07 | 一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112972641B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116920066B (zh) * | 2023-09-09 | 2024-04-26 | 中国中医科学院望京医院(中国中医科学院骨伤科研究所) | 一种治疗肺结节及肺癌的中药组合物及其制剂和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111588825A (zh) * | 2020-07-03 | 2020-08-28 | 重庆市中医院 | 一种用于治疗骨转移瘤带来的癌痛的中药组合物及其制备方法和应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103610873B (zh) * | 2013-11-20 | 2017-04-12 | 冯利 | 一种治疗癌性躯体痛的中药组合物 |
-
2021
- 2021-02-07 CN CN202110174580.6A patent/CN112972641B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111588825A (zh) * | 2020-07-03 | 2020-08-28 | 重庆市中医院 | 一种用于治疗骨转移瘤带来的癌痛的中药组合物及其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112972641A (zh) | 2021-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wu et al. | Network pharmacology and molecular docking study of the Chinese miao medicine sidaxue in the treatment of rheumatoid arthritis | |
| CN116392563B (zh) | 一种治疗乳腺结节的中药组合物及其制剂和应用 | |
| CN112972641B (zh) | 一种治疗骨转移癌性躯体痛的中药组合物及其制备方法和应用 | |
| Bai et al. | Effects of Integrated Chinese Traditional Medicine and Conventional Western Medicine on the Quality of Life of Breast Cancer Patients: A Systematic Review and Meta‐Analysis | |
| CN101785810B (zh) | 一种治疗过敏性紫癜的中药制剂 | |
| CN100548282C (zh) | 一种治疗肝癌的药物 | |
| CN105106337A (zh) | 一种治疗类风湿关节炎的雷公藤药酒 | |
| CN103599453B (zh) | 一种治疗脾胃虚弱型胃癌的中药及其制备方法 | |
| CN102552593B (zh) | 一种用于治疗风寒湿痹的中药组合物 | |
| Li | [Retracted] Effect of Warming Yang, Tonifying Kidney, and Removing Arthralgia Therapy on Cold‐Dampness Arthralgia Type Ankylosing Spondylitis and Its Influence on the Levels of Humoral Factor in Human Serum | |
| CN104888153A (zh) | 一种治疗肝血管瘤的中药制剂及其制备方法 | |
| Zhang et al. | Therapeutic efficacy evaluation and mechanism of action based on meta-analysis and network pharmacology of Li Chong Decoction (Bolus) for cancer treatment. | |
| CN104288489A (zh) | 一种用于治疗乳腺肿瘤的药物及其制备方法 | |
| Li et al. | Computational systems pharmacology analysis of Tong-Jing-Yi formula in the treatment of dysmenorrhea | |
| CN100418573C (zh) | 一种治疗强直性脊柱炎的外用中药 | |
| CN103520638B (zh) | 一种治疗前列腺肥大症的中药复方组合物及其制备方法及其应用 | |
| Dong et al. | To explore the mechanism of huangqi guizhi wuwu decoction in the treatment of rheumatoid arthritis based on network pharmacology | |
| Liu et al. | Molecular mechanism of Duhuojisheng Decoction in the treatment of knee osteoarthritis based on the network pharmacology. | |
| CN104491799B (zh) | 一种用于贴敷治疗类风湿关节炎的中药散剂 | |
| CN101361955B (zh) | 一种治疗类风湿疾病的中药组合物 | |
| CN1679908A (zh) | 一种治疗肿瘤的中药及其制备方法 | |
| Sun et al. | Exploration of the Mechanism of Sinisan Formula in Functional constipation and Somatic Symptom Disorders with the Concept of “Different Diseases with the Same Treatment” Based on Network Pharmacology and Molecular Docking | |
| Xue et al. | Clinical Observation of Integrated Traditional Chinese and Western Medicine in the Treatment of Chronic Ulcerative Rectitis | |
| Mei et al. | Effect of regulating qi and invigorate blood circulation method on hemorrheology in rats with acute blood stasis syndrome and its network pharmacology research | |
| Seca | Effects of acupuncture on the pain and function of the hands of selected patients with rheumatoid arthritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |