CN115120689A - 欣力康复方制剂在制备药物中的应用 - Google Patents
欣力康复方制剂在制备药物中的应用 Download PDFInfo
- Publication number
- CN115120689A CN115120689A CN202210529449.1A CN202210529449A CN115120689A CN 115120689 A CN115120689 A CN 115120689A CN 202210529449 A CN202210529449 A CN 202210529449A CN 115120689 A CN115120689 A CN 115120689A
- Authority
- CN
- China
- Prior art keywords
- leukemia
- weight
- rehabilitation
- preparation
- xinli
- 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 65
- 239000003814 drug Substances 0.000 title abstract description 51
- 229940079593 drug Drugs 0.000 title description 29
- 208000032839 leukemia Diseases 0.000 claims abstract description 91
- 208000035762 Disorder of lipid metabolism Diseases 0.000 claims abstract description 3
- 206010015535 Euphoric mood Diseases 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000000463 material Substances 0.000 claims description 16
- 230000002743 euphoric effect Effects 0.000 claims description 13
- 238000009472 formulation Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 9
- 240000002853 Nelumbo nucifera Species 0.000 claims description 8
- 235000006508 Nelumbo nucifera Nutrition 0.000 claims description 8
- 235000006510 Nelumbo pentapetala Nutrition 0.000 claims description 8
- 244000084767 Potentilla indica Species 0.000 claims description 8
- 235000002594 Solanum nigrum Nutrition 0.000 claims description 8
- 241001643392 Cyclea Species 0.000 claims description 7
- 235000002789 Panax ginseng Nutrition 0.000 claims description 7
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 claims description 7
- 240000002307 Solanum ptychanthum Species 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 235000001287 Guettarda speciosa Nutrition 0.000 claims description 6
- 235000006533 astragalus Nutrition 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 5
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
- 241001061264 Astragalus Species 0.000 claims description 5
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 5
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 5
- 210000004233 talus Anatomy 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 238000005520 cutting process Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000001694 spray drying Methods 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 240000002045 Guettarda speciosa Species 0.000 claims 2
- 240000007164 Salvia officinalis Species 0.000 claims 1
- 244000132619 red sage Species 0.000 claims 1
- 235000005412 red sage Nutrition 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 39
- 210000002966 serum Anatomy 0.000 abstract description 37
- 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 36
- 210000004027 cell Anatomy 0.000 abstract description 35
- 210000004369 blood Anatomy 0.000 abstract description 29
- 239000008280 blood Substances 0.000 abstract description 29
- 210000000952 spleen Anatomy 0.000 abstract description 26
- 210000004185 liver Anatomy 0.000 abstract description 17
- 208000030159 metabolic disease Diseases 0.000 abstract description 9
- 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 abstract description 8
- 108090001005 Interleukin-6 Proteins 0.000 abstract description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 8
- 210000005229 liver cell Anatomy 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 6
- 230000002757 inflammatory effect Effects 0.000 abstract description 6
- 150000002632 lipids Chemical class 0.000 abstract description 5
- 230000006378 damage Effects 0.000 abstract description 4
- 230000008595 infiltration Effects 0.000 abstract description 4
- 238000001764 infiltration Methods 0.000 abstract description 4
- 238000009825 accumulation Methods 0.000 abstract description 2
- 230000007850 degeneration Effects 0.000 abstract description 2
- 208000010706 fatty liver disease Diseases 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 210000000265 leukocyte Anatomy 0.000 abstract description 2
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 230000008439 repair process Effects 0.000 abstract description 2
- 235000021588 free fatty acids Nutrition 0.000 abstract 1
- 238000010874 in vitro model Methods 0.000 abstract 1
- 230000037361 pathway Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 36
- 241001539473 Euphoria Species 0.000 description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 241000700159 Rattus Species 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 11
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 10
- 108010082126 Alanine transaminase Proteins 0.000 description 10
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 10
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 10
- 230000003211 malignant effect Effects 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol 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)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 8
- 229960004618 prednisone Drugs 0.000 description 8
- 125000002324 prednisone group Chemical group 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 208000014951 hematologic disease Diseases 0.000 description 7
- 241000304195 Salvia miltiorrhiza Species 0.000 description 6
- 230000037356 lipid metabolism Effects 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 244000061520 Angelica archangelica Species 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 235000009508 confectionery Nutrition 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 3
- 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 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000003805 procoagulant Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 238000005728 strengthening Methods 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 241000382455 Angelica sinensis Species 0.000 description 2
- 241000208340 Araliaceae Species 0.000 description 2
- 239000009636 Huang Qi Substances 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
- 235000003140 Panax quinquefolius Nutrition 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940107666 astragalus root Drugs 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000035619 diuresis Effects 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 230000006372 lipid accumulation Effects 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000007863 steatosis Effects 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000045403 Astragalus propinquus Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 244000008991 Curcuma longa Species 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 244000071493 Iris tectorum Species 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 244000061457 Solanum nigrum Species 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000040 effect on leukemia Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000028503 regulation of lipid metabolic process Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 229960005486 vaccine Drugs 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)
- A61K36/48—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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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
- A61K36/285—Aucklandia
-
- 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)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- 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)
- A61K36/59—Menispermaceae (Moonseed family), e.g. hyperbaena or coralbead
-
- 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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- 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)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
-
- 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)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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, 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
-
- 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
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Abstract
本发明公开了欣力康复方制剂在制备治疗白血病、脂代谢紊乱或两者合并症药物中的应用。本发明通过构建代谢相关性脂肪性肝病体内外模型，经筛选发现欣力康复方制剂可降低白血病组小鼠脂质在肝细胞中的蓄积，降低血清中炎症因子(IL‑6、TNF‑α)和血糖的含量、减少血清中游离脂肪酸含量抑制脂质代谢通路紊乱，有效抑制了小鼠脾脏中白细胞的浸润及小鼠肝脏脂肪变，并一定程度上修复了白血病细胞对小鼠脾脏的损伤，显示欣力康复方制剂能够有效抑制白血病合并代谢紊乱的进一步发生和发展；未来将其应用于白血病合并代谢紊乱的治疗，为白血病合并代谢紊乱患者提供新的用药选择，对当前世界白血病合并代谢紊乱患者的治疗具有重要作用和意义。
Description
技术领域
本发明属于中药新用途技术领域，具体涉及欣力康复方制剂在制备治疗白血病、脂代谢紊乱或两者合并症药物中的应用。
背景技术
欣力康为民族药配方制剂，由贵阳新天药业股份有限公司生产制造，具有补气养血，化瘀解毒之功效，临床用于乳腺癌、肺癌、膀胱癌等癌症放化疗的辅助治疗。主要原料成分包括黄芪、当归、龙葵、郁金、红参、蛇莓、雪莲花、轮环藤根、丹参药材。
白血病(leukemia)是一类造血干细胞或造血祖细胞的恶性克隆性肿瘤。中医认为其实由于正气内虚、温热毒邪乘虚而入引起的，以热毒、血瘀、痰浊互结，人体伤血为基本病机，以发热、出血、贫血及肝、脾、淋巴结肿大等为主要临床表现的一种造血系统的恶性肿瘤，因为恶性增殖、凋亡障碍和分化受阻等因素形成的白血病细胞在骨髓、脾和肝等组织器官中大量增殖积累和广泛浸润，并且抑制骨髓的正常造血功能。据统计，2018年全球白血病患者新增43.7万例，死亡30.9万例，而且白血病占所有儿童癌症(包括良性和交界性恶性脑肿瘤)的29％，严重威胁人类的健康，开发能有效治疗白血病的药物是全球白血病患者的迫切希望；如不加以控制，随着白血病细胞的快速增殖及免疫功能的损伤，可进一步导致白血病患者脂质代谢紊乱如糖尿病、非酒精性脂肪肝病等并发症的出现，而脂代谢紊乱进一步加剧了白血病患者的病程进展、治疗难度和死亡风险。据相关机构统计表明60％的白血病患者均有白血病合并脂代谢紊乱，所以在抑制白血病发展过程的同时也可调节脂代谢异常是未来治疗白血病的一种重要途径。因此，开发白血病合并脂代谢紊乱的治疗药物具有重要的社会意义和医学研究价值。
目前，白血病的治疗尚缺乏理想的治疗药物，以往白血病的临床的治疗方法主要包括化疗、分化治疗、靶向治疗、单克隆抗体治疗及干细胞移植等，而化疗仍然是大多数白血病患者的首选疗法。化疗药物对白血病患者毒副作用强，导致患者生存质量严重下降，且存在靶点单一，易复发等缺点；此外，白血病合并脂代谢紊乱是涉及癌细胞恶性增殖、代谢紊乱及免疫系统损伤等因素共同导致，西医学难以通过单一靶点来有效根治白血病合并脂代谢紊乱。因此，寻找一种有效、安全的白血病合并脂代谢紊乱治疗药物已成为当务之急。
发明内容
本发明目的在于提供欣力康复方制剂在制备治疗白血病合并脂代谢紊乱药物中的应用；制剂明显降低了白血病模型小鼠脾的大小和重量，同时显著抑制了白血病小鼠脾脏中大量嗜碱性白血病细胞的浸润，脾脏正常结构得以恢复。
为达到上述目的，本发明的技术方案为：
欣力康复方制剂在制备治疗白血病、脂代谢紊乱或两者合并症药物中的应用，所述欣力康复方制剂由黄芪300重量份、当归300重量份、龙葵250重量份、郁金250重量份、红参250重量份、蛇莓200重量份、雪莲花200重量份、轮环藤根200重量份和丹参200重量份为原料药制成。
前述欣力康复方制剂的应用，所述白血病为急性髓细胞白血病、急性淋巴细胞白血病、慢性髓细胞白血病或慢性淋巴细胞白血病；所述脂代谢紊乱疾病为非酒精性脂肪肝或糖尿病。
前述欣力康复方制剂的应用，所述欣力康复方制剂的制法为：称取黄芪、当归、龙葵、郁金、红参、蛇莓、雪莲花、轮环藤根、丹参，切段、混匀后加水煎煮二次，第一次加水量为药材重量的4倍，煎煮3小时，第二次加水量为药材重量的3倍，煎煮1小时，合并煎液，滤过，滤液减压浓缩至80℃相对密度为1.25，喷雾干燥成干粉浸膏，然后加入辅料或者不加辅料制成各种口服制剂。
前述欣力康复方制剂的应用，所述欣力康复方制剂是在浸膏中加入适量的淀粉、糊精、蔗糖、羟苯乙酯为辅料，混匀，制成颗粒，干燥，分装制成的胶囊制剂。
中医学，是祖国医学的重要组成部分。中医学是在阴阳五行理论指导下，从动态和整体的角度，研究人体的生理、病理与自然环境关系，并涉及药理、寻求防治疾病方法的学问。在中医学历代医家的论著中，骨髓增生异常综合征属于“虚痨”、“血证”的范畴，近代医家、学者继承并吸取现代医学知识，结合临床特点和一般表现，在2008年将骨髓增生异常综合征，创新命名为“髓毒劳”。“髓”主要代表病位，“毒”主要代表病性，“劳”主要代表病状，实现了中医病名与临床特征、病机、病位的辩证。历代医家认为在恶性血液病发生、发展过程中，“毒”邪具有重要作用，且在历代医家论著中，“毒”涉及恶性血液病发生、发展乃至辩证施治的始终。《黄帝内经》中关于六淫邪气论述中，认为偏盛之气侵袭机体方可化生为毒。《诸病源候论》指出:“此由风气相博，变成热毒。”、“此由表实里虚，热气乘虚而入，攻于脾胃，则下黄赤汁，此热毒所为也。”。《内经》记载中，毒邪是指具有强烈致病作用，对人体毒害是有别于六淫的特殊病因。中医感染毒邪在恶性血液病中的表现有白血病、淋巴瘤等，其发病均有感染病毒的因素。因此，中医临床上根据恶性血液疾病的特点运用散寒解毒、祛风化痰、清利湿毒、补益精气、健脾补肾、清热化瘀等法来治疗。
欣力康复方制剂的功效主要为：补气养血，化瘀解毒。方中红参甘苦温，补元气，复脉固脱，益气摄血，为君药。丹参苦寒，活血祛瘀，通经止痛，清心除烦，凉血消痈，为臣药。郁金辛苦寒，行气化瘀，清心解郁，利胆退黄，为臣药。黄芪甘温，健脾补中，升阳举陷，益卫固表，利尿，托毒生肌，为佐药。当归辛甘温，补血活血，调经止痛，润肠通便，为佐药。蛇莓甘苦寒，清热，凉血，消肿，解毒，为佐药。龙葵苦寒，清热，解毒，活血，消肿，为使药。雪莲花甘温，除寒，壮阳，调经，止血，为使药。轮环藤根苦寒，清热解毒，利尿通淋，祛风止痛，为使药。本方活血通络，化瘀止痛，护肝健脾，具有消肿化瘀、抗癌、止痛之功效。中医在整体观念、辨证论治理论指导下，通过多途径、多靶点、整体调节等特点，临床上对白血病模型的治疗效果显著、不良反应少、价格低廉、不容易出现耐药等明显的优势，已成为治疗该病的重要手段，也为研发治疗白血病合并脂代谢紊乱的新药提供了新方向。
相对于现有技术，本发明的有益效果为：
本发明首次公开欣力康复方制剂对白血病、脂代谢紊乱或两者合并症的治疗作用。本发明通过白血病、脂代谢紊乱以及两者合并症的动物模型和细胞模型对多个贵州民族药复方制剂进行了活性筛选，首次发现贵州民族药苗药复方制剂“欣力康”有新的用途，其既能治疗单一的白血病或脂代谢紊乱，又对白血病合并脂代谢紊乱病症有显著疗效。实验发现，欣力康复方制剂对白血病细胞Jurkat、HEL和K562具有较强抑制活性，其处理48h后，其中Jurkat的IC50值为193.64±15.13μg/ml，HEL的IC50值为231.69±16.93μg/ml，K562的IC50值为245.50±5.67μg/ml；欣力康复方制剂能通过作用于多个靶点抑制白血病病程进展及其诱发的脂代谢异常并发症，给药后白血病模型小鼠脾的大小和重量明显降低，同时显著抑制了白血病小鼠脾脏中大量嗜碱性白血病细胞的浸润，脾脏正常结构得以恢复；此外，欣力康给药组明显抑制了白血病模型组小鼠肝脏的大泡性脂肪变，降低了白血病模型组小鼠肝重及脂质积累；另外，给药组降低血清中炎症因子(IL-6、TNF-α)、血糖的含量、脂质含量显著降低，脂质合成基因的表达水平下调。预期欣力康复方制剂未来可应用于白血病合并脂代谢紊乱的治疗，为白血病合并脂代谢紊乱患者提供了新的用药选择，对当前世界恶性血液疾病—白血病及其诱发脂代谢紊乱的治疗具有重要作用和意义。
附图说明
图1不同浓度欣力康复方制剂处理48h后对白血病细胞Jurkat、HEL和K562增殖的抑制效果；A-白血病细胞Jurkat；B-白血病细胞HEL；C-白血病细胞K562；
图2流式细胞仪分析不同浓度欣力康复方制剂对白血病细胞Jurkat凋亡的影响；
图3流式细胞仪分析不同浓度欣力康复方制剂对白血病细胞HEL凋亡的影响；
图4流式细胞仪分析不同浓度欣力康复方制剂对白血病细胞K562凋亡的影响；
图5 H&E染色观察欣力康复方制剂对白血病合并脂代谢紊乱模型小鼠肝的保护及脾脏结构的修复效果；XLK：欣力康复方制剂处理组，PRS：泼尼松组，M：白血病合并脂代谢紊乱模型组，CN：正常组小鼠；
图6欣力康复方制剂对白血病合并脂代谢紊乱模型小鼠心、肝、脾、肺、肾重量的影响；
图7欣力康复方制剂对白血病合并脂代谢紊乱模型小鼠血容比的影响；
图8欣力康复方制剂处理对小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三脂(TG)、总胆固醇(TC)和血糖(GLU)含量的影响；XLK：欣力康复方制剂处理组，PRS：泼尼松组，M：白血病合并脂代谢紊乱模型组，CN：正常组；
图9欣力康复方制剂对小鼠血清中炎症因子(IL-6和TNF-α)的调节效果；XLK：欣力康复方制剂处理组，PRS：泼尼松组，M：白血病合并脂代谢紊乱模型组，CN：正常组；
图10欣力康复方制剂大鼠含药血清对脂代谢紊乱细胞模型脂质含量的影响；5％、10％、15％：不同浓度欣力康制剂大鼠含药血清，M：脂代谢紊乱细胞模型，CN：正常组；
图11欣力康复方制剂大鼠含药血清处理48h后对白血病细胞Jurkat、HEL和K562增殖的抑制效果；5％、10％、15％：不同浓度欣力康制剂大鼠含药血清，CN：正常组。
具体实施方式
本发明实施例1：欣力康复方制剂的应用：
市场上购买欣力康胶囊，所得胶囊剂可直接用于治疗白血病(白血病为急性髓细胞白血病、急性淋巴细胞白血病、慢性髓细胞白血病或慢性淋巴细胞白血病)合并脂代谢紊乱(非酒精性脂肪肝或糖尿病)。用法用量：口服，一次3-5粒，一日3次。
实施例2：欣力康复方制剂的应用：
称取黄芪300g、当归300g、龙葵250g、郁金250g、红参250g、蛇莓200g、雪莲花200g、轮环藤根200g和丹参200g，切碎段、混匀后加水煎煮二次，第一次加水量为药材重量的5倍，煎煮4小时，第二次加水量为药材重量的4倍，煎煮2小时，合并煎液，滤过，滤液减压浓缩至80℃相对密度为1.25，微波干燥成清干膏，粉碎为100目粉，然后加入辅料淀粉和糊精，制粒，干燥，装入胶囊，即得。
所得胶囊剂直接用于治疗白血病(急性髓细胞白血病、急性淋巴细胞白血病、慢性髓细胞白血病或慢性淋巴细胞白血病)合并脂代谢紊乱(非酒精性脂肪肝或糖尿病)。用法用量：口服，一次3-5粒，一日3次。
实施例3：欣力康复方制剂的应用：
称取黄芪300g、当归300g、龙葵250g、郁金250g、红参250g、蛇莓200g、雪莲花200g、轮环藤根200g和丹参200g，采用常规提取工艺和制剂成型工艺制成各种口服制剂。
所得口服制剂直接用于治疗代谢相关性脂肪性肝病(非酒精性脂肪肝或糖尿病)。用法用量：口服，一次1.5-2.5g，一日3次。
实施例4：欣力康复方制剂的应用：
称取黄芪300g、当归300g、龙葵250g、郁金250g、红参250g、蛇莓200g、雪莲花200g、轮环藤根200g和丹参200g，切段、混匀后加水煎煮二次，第一次加水量为药材重量的4倍，煎煮2小时，第二次加水量为药材重量的3倍，煎煮1.5小时，合并煎液，静置24小时，取上清液浓缩至总量的70％，所得药液加入辅料或者不加辅料制成各种口服制剂。
所得口服制剂直接用于治疗白血病(急性髓细胞白血病、急性淋巴细胞白血病、慢性髓细胞白血病或慢性淋巴细胞白血病)。用法用量：口服，一次1.5-2.5g，一日3次。
实验例：
1.实验材料
1.1材料及方法
SPF级BALBc小鼠，出生48h后注射诱导白血病的Friend病毒，共40只；正常鼠10只；BALBc小鼠为实验室繁殖；SD大鼠，雄鼠，体重200±20g，共20只，购自南京模式动物研究所。小鼠饲喂生长繁殖饲料和高脂饲料，大鼠饲喂生长繁殖饲料，均由上海华雅思创生物公司生产，饮用水为灭菌自来水，试验期间动物自由采食饮水，实验室温度21±2℃，湿度40-70％，实验室许可证号：SYXK(黔)2018-0001。实验用HepG2细胞、DMEM高糖培养基购自武汉普诺赛生命科技有限公司。Gibco胎牛血清购自赛默飞世尔科技有限公司。
1.2仪器
台式离心机(Beckman)，生物安全柜(Thermo Scientific)，细胞培养箱(ThermoScientific)，荧光倒置显微镜(Olympus)，恒温水浴锅(Grant)，高压蒸汽灭菌锅(Shenan)，Milli-Q制水机(BioGen)，多功能酶标仪(Bio tek)。
1.3分组及建立白血病模型模型
注射病毒6周后分笼。将40只小鼠，随机分为4组，每组10只。分别为：模型组、阳性对照组、欣力康制剂组。所有组小鼠均用正常繁殖饲料和灭菌水喂养，持续饲喂8周。
1.4分组给药
实验从小鼠6周龄开始灌胃给药。给予本发明欣力康制剂3.37g生药/kg灌胃给药，阳性药组给予泼尼松10mg/kg；正常组及模型组灌胃等体积的生理盐水，每日一次，连续给药8周。给药期间，除正常组外，各组小鼠均继续造模。小鼠每周称一次体重，按体重变化给药量。SD大鼠分为两组(正常组和给药组，各5只)，给药剂量为2.35g/kg，连续给药7天。
1.5实验动物处理
给药8周末，动物禁食不禁水12h，称重。各组小鼠以10％水合氯醛麻醉后，脱臼处死小鼠，眼眶取血，收取小鼠血清。并测定各组小鼠血容比。取小鼠肝脏冻存于-80℃冰箱中进行后续进行分析检测。
1.6检测指标
1.6.1肝脏和脾样品
给药结束后取小鼠肝脏部分样品和脾样品送至武汉赛维尔生物科技有限公司，对肝脏组织和脾进行病理分析(H&E染色)。
1.6.2酶标仪检测各组小鼠血清样品中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三脂(TG)、总胆固醇(TC)、血糖(Glu)含量
小鼠血液生化指标的检测，用1.5制备好的小鼠血清样本采用南京检测生物制品有限公司生产的试剂盒通过酶标仪来检测ALT、AST、TG、TC、Glu等指标含量。
1.6.3酶联免疫吸附剂术(ELISA)检测各组小鼠血清中IL-6、TNF-α含量
小鼠血液生化指标的检测，用1.5制备好的小鼠血清样本采用ELISA试剂盒通过酶标仪来检测IL-6、TNF-α等指标。
1.7欣力康复方制剂含药血清对肝细胞脂质代谢异常模型和白血病细胞的作用效果
(1)建立体外肝细胞脂质代谢异常模型：采用0.5mM浓度的油酸处理HepG2细胞24h，建立肝细胞脂质代谢异常模型。随后通过欣力康复方制剂大鼠含药血清处理肝细胞脂质代谢异常模型，检测含药血清对肝细胞脂质代谢异常模型脂质代谢的影响。
(2)采用欣力康大鼠含药血清分别处理白血病细胞Jurkat、K562和HEL，利用MTT法和流式细胞仪检测欣力康大鼠含药血清对白血病细胞增殖的影响。
欣力康复方制剂大鼠含药血清制取：
a.用欣力康复方总提取物灌胃正常6周龄，体重200±20g SD大鼠，给药剂量为2.35g/kg，每天一次，连续给药7天。
b.最后一次给药后，禁食不禁水4-8h后开始收集血清。
c.取血前，先用水合氯醛对SD大鼠进行麻醉。
d.待麻药起作用后，打开SD大鼠腹腔，通过腹主动脉将大鼠血清收集到促凝管中。
e.将促凝管常温放置1-2h，待血完全凝固后，将促凝管置于离心机中4000rpm15min，收集上清，即为含药血清。
f.血清收集完后，将血清置于56℃水浴中灭活30min。将灭活的含药血清用0.22μm微孔滤膜过滤后置于-20℃冰箱保存。
1.8统计方法
实验结果采用SPSS 22.0统计软件，所有数据采用均数±标准差表示，两两比较采用t检验p<0.05为差异有统计学意义。
2实验结果
2.1欣力康复方制剂处理组对小鼠体重的影响
如图1所示，对照各组实验结果可以看出，处理48小时后，欣力康复方制剂对Jurkat、HEK和K562细胞活性的抑制效果随着浓度的增加呈现逐渐增加的趋势(图1中A、B和C)，对上述三种细胞的IC50值分别为193.64±15.13μg/ml、231.69±16.93μg/ml和245.50±5.67μg/ml(表1)。此外，流式细胞仪检测结果也显示，欣力康复方制剂处理48h后Jurkat、HEK和K562三种细胞的凋亡率随着浓度的增加呈现剂量依赖效应(图2、图3、图4)。
表1欣力康复方制剂对白血病细胞Jurkat、HEL和K562的IC50
2.2欣力康复方制剂处理组对白血病模型小鼠大泡性脂肪变的影响
H&E染色显示高脂诱导的白血病模型小鼠均有点状坏死及炎细胞浸润出现及不同程度的脂肪变性及空泡样变，同时白血病模型组小鼠肝脏明显大于欣力康方剂(XLK)组及泼尼松(PRS)组(图5)，且其肝呈现不同程度的乳白色(图5)。油红O染色结果显示，相比模型组小鼠，XLK和PRS组小鼠肝脏中脂肪含量明显减少(图5)。所述欣力康方剂(XLK)处理后明显改善了小鼠肝脏脂肪变性、空泡样变及脂质蓄积，同时小鼠肝脏形态与正常组趋于一致(图5)。此外，通过H&E染色发现与模型组相比，PRS和XLK组小鼠脾中嗜碱性白血病细胞显著降低，且脾的结构得到修复(图5)。上述结果可显示，欣力康方剂有效抑制了小鼠脾脏中白细胞的浸润，并在一定程度上修复了白血病细胞对小鼠脾脏的损伤。
2.3分析欣力康方剂对各组小鼠心、肝、脾、肺和肾的影响
如图6所示，相比模型组，XLK和PRS组明显降低了小鼠肝脏的重量(p<0.001)及小鼠脾的重量(p<0.01和p<0.001)(图6中B和C)，但对小鼠心脏、肺和肾脏的重量没有影响(图6中A、D和E)。上述数据结果表明，欣力康方剂可有效降低模型组小鼠肝脏和脾的重量，且与阳性药PRS的效果相当。
2.4欣力康方剂对小鼠血容比的影响
如图7所示，相比模型组，XLK和PRS组均提升了小鼠的血容比，且XLK组小鼠血容比显著高于模型组(p<0.05)。通过血容比数据分析显示欣力康方剂对白血病小鼠的改善效果明显优于阳性药组PRS。
2.5欣力康复方制剂处理组对白血病合并代谢紊乱模型小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三脂(TG)、总胆固醇(TC)、血糖(Glu)含量的影响
为进一步分析欣力康复方制剂对白血病合并代谢紊乱模型小鼠的治疗效果，实验还测定了各组小鼠血清中ALT、AST、TG、TC、Glu等生化指标含量。如图8所示，相比正常组，欣力康复方制剂降低了小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三脂(TG)、总胆固醇(TC)和血糖(Glu)含量，且对小鼠血清中TC和TG的含量的提升效果明显优于阳性药PRS组。
2.6欣力康复方制剂处理组对白血病合并代谢紊乱模型小鼠血清中炎症因子IL-6和TNF-α含量的影响
为进一步探究欣力康复方制剂是否可抑制脂质过氧化引起的小鼠体内炎症反应，实验利用Elisa方法分别测定了小鼠血清中炎症因子IL-6和TNF-α的含量。如图9所示，从对照各组实验结果可以看出，欣力康复方制剂降低了小鼠血清中炎症因子IL-6和TNF-α含量，抑制了白血病合并代谢紊乱模型小鼠体内的炎症反应。
2.7欣力康复方制剂含药血清对脂质紊乱细胞模型和白血病细胞活性的作用效果
利用油酸处理人肝脏细胞建立脂质代谢紊乱模型体外细胞模型，随后用欣力康复方制剂大鼠含药血清处理白血病模型细胞模型，明确欣力康复方制剂含药血清对人肝细胞脂代谢紊乱模型的作用效果。如图10所示，从对照各组实验结果可以看出，欣力康复方制剂显著降低了白血病模型细胞模型中脂质的蓄积。此外，通过MTT测定显示，Jurkat、HEK和K562细胞活性随着欣力康复方制剂含药血清浓度(5％，10％，15％)的增加呈现逐渐降低的趋势(图11)。
Claims (4)
1.欣力康复方制剂在制备治疗白血病、脂代谢紊乱或两者合并症药物中的应用，所述欣力康复方制剂由黄芪300重量份、当归300重量份、龙葵250重量份、郁金250重量份、红参250重量份、蛇莓200重量份、雪莲花200重量份、轮环藤根200重量份和丹参200重量份为原料药制成。
2.根据权利要求1所述欣力康复方制剂的应用，其特征在于：所述白血病为急性髓细胞白血病、急性淋巴细胞白血病、慢性髓细胞白血病或慢性淋巴细胞白血病；所述脂代谢紊乱疾病为非酒精性脂肪肝或糖尿病。
3.根据权利要求1所述欣力康复方制剂的应用，其特征在于：所述欣力康复方制剂的制法为：称取黄芪、当归、龙葵、郁金、红参、蛇莓、雪莲花、轮环藤根、丹参，切段、混匀后加水煎煮二次，第一次加水量为药材重量的4倍，煎煮3小时，第二次加水量为药材重量的3倍，煎煮1小时，合并煎液，滤过，滤液减压浓缩至80℃相对密度为1.25，喷雾干燥成干粉浸膏，然后加入辅料或者不加辅料制成各种口服制剂。
4.根据权利要求3所述欣力康复方制剂的应用，其特征在于：所述欣力康复方制剂是在浸膏中加入适量的淀粉、糊精、蔗糖、羟苯乙酯为辅料，混匀，制成颗粒，干燥，分装制成的胶囊制剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210529449.1A CN115120689A (zh) | 2022-05-16 | 2022-05-16 | 欣力康复方制剂在制备药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210529449.1A CN115120689A (zh) | 2022-05-16 | 2022-05-16 | 欣力康复方制剂在制备药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115120689A true CN115120689A (zh) | 2022-09-30 |
Family
ID=83376943
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210529449.1A Pending CN115120689A (zh) | 2022-05-16 | 2022-05-16 | 欣力康复方制剂在制备药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115120689A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116270787A (zh) * | 2022-12-14 | 2023-06-23 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 一种中西复方药物在制备治疗白血病药物中的应用 |
-
2022
- 2022-05-16 CN CN202210529449.1A patent/CN115120689A/zh active Pending
Non-Patent Citations (2)
| Title |
|---|
| 沈剑等: ""欣力康胶囊对肿瘤细胞增殖抑制作用初探"", 《中国中西医结合外科杂志》, vol. 24, no. 1, 28 February 2018 (2018-02-28), pages 79 - 82 * |
| 许济群等: "《贵州省药品微生物检验方法汇编》", vol. 1, 30 June 1985, 上海科技出版社, pages: 113 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116270787A (zh) * | 2022-12-14 | 2023-06-23 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 一种中西复方药物在制备治疗白血病药物中的应用 |
| CN116270787B (zh) * | 2022-12-14 | 2024-03-08 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 一种中西复方药物在制备治疗白血病药物中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103861079B (zh) | 一种清热止痛消瘤中药组合物 | |
| CN103768534A (zh) | 一种具有抗肿瘤活性的中药组合物 | |
| CN103446525B (zh) | 治疗皮肤病的中药组合物及其制备方法和应用 | |
| CN101711848B (zh) | 一种辅助治疗肿瘤的中药组合物 | |
| CN103223131B (zh) | 肝病药物 | |
| CN115120689A (zh) | 欣力康复方制剂在制备药物中的应用 | |
| CN101780227B (zh) | 一种治疗中风急性期的中药组合物及其制备方法 | |
| CN104857435A (zh) | 一种具有抗肿瘤活性的中药复方组合物及其制备方法和应用 | |
| CN105688034A (zh) | 一种中药组合物在制备治疗胆囊切除术后综合征的药物中的应用 | |
| CN103705796A (zh) | 一种治疗腹泻的药物组合物及其制备方法 | |
| CN108434239A (zh) | 补气血抗疲劳口服液及其制备方法 | |
| CN104491459A (zh) | 一种治疗肿瘤的中药组合物 | |
| CN100528186C (zh) | 一种治疗慢性肾功能衰竭中药复方注射剂的制备工艺以及应用 | |
| CN104189781A (zh) | 一种治疗神经胶质瘤的中药组合物 | |
| CN110448625B (zh) | 一种治疗缺氧性肾损伤疾病的中药组合物、制备方法及其应用 | |
| CN103719661B (zh) | 补血口服液保健品 | |
| CN101991757B (zh) | 一种补肾助阳的中药组合物及其制备方法 | |
| CN112220846A (zh) | 一种治疗小儿久咳的中药组合物及其应用 | |
| CN105902951A (zh) | 联合化疗药治疗骨肉瘤的中药复方组合物 | |
| CN101045116B (zh) | 一种治疗胆囊炎的中药药物 | |
| CN116270787B (zh) | 一种中西复方药物在制备治疗白血病药物中的应用 | |
| CN103191268B (zh) | 一种治疗肺癌的中药组合物 | |
| CN111298061B (zh) | 一种清热解毒、祛瘀散结的中药组合物及其制备方法 | |
| CN109091636B (zh) | 一种治疗冠心病的壮药配方及其制备方法 | |
| CN102423384A (zh) | 一种治疗肺癌的中药制剂及其制备方法 |
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 |