CN114949142B - Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof - Google Patents
Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof Download PDFInfo
- Publication number
- CN114949142B CN114949142B CN202210598584.1A CN202210598584A CN114949142B CN 114949142 B CN114949142 B CN 114949142B CN 202210598584 A CN202210598584 A CN 202210598584A CN 114949142 B CN114949142 B CN 114949142B
- Authority
- CN
- China
- Prior art keywords
- parts
- chinese medicine
- traditional chinese
- medicine composition
- preparation
- 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 75
- 239000000203 mixture Substances 0.000 title claims abstract description 72
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 46
- 108091092878 Microsatellite Proteins 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 25
- 206010027476 Metastases Diseases 0.000 claims abstract description 24
- 230000009401 metastasis Effects 0.000 claims abstract description 24
- 210000004185 liver Anatomy 0.000 claims abstract description 19
- 244000307697 Agrimonia eupatoria Species 0.000 claims abstract description 14
- 244000077995 Coix lacryma jobi Species 0.000 claims abstract description 14
- 235000000125 common agrimony Nutrition 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 22
- 239000000052 vinegar Substances 0.000 claims description 21
- 235000021419 vinegar Nutrition 0.000 claims description 21
- 239000000284 extract Substances 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 11
- 241000037740 Coptis chinensis Species 0.000 claims description 10
- 241000132012 Atractylodes Species 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000001694 spray drying Methods 0.000 claims description 7
- 238000000889 atomisation Methods 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000009636 Huang Qi Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 3
- 206010027457 Metastases to liver Diseases 0.000 claims description 2
- 230000000887 hydrating effect Effects 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 238000000194 supercritical-fluid extraction Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 34
- 229940079593 drug Drugs 0.000 abstract description 16
- 210000004072 lung Anatomy 0.000 abstract description 14
- 210000000952 spleen Anatomy 0.000 abstract description 10
- 230000006907 apoptotic process Effects 0.000 abstract description 8
- 210000004369 blood Anatomy 0.000 abstract description 8
- 239000008280 blood Substances 0.000 abstract description 8
- 229940107666 astragalus root Drugs 0.000 abstract description 7
- 230000001105 regulatory effect Effects 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 230000035755 proliferation Effects 0.000 abstract description 6
- 241000721047 Danaus plexippus Species 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 239000002671 adjuvant Substances 0.000 abstract description 3
- 230000001276 controlling effect Effects 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 235000002991 Coptis groenlandica Nutrition 0.000 abstract description 2
- 238000005728 strengthening Methods 0.000 abstract description 2
- 244000247747 Coptis groenlandica Species 0.000 abstract 1
- 206010009944 Colon cancer Diseases 0.000 description 35
- 206010028980 Neoplasm Diseases 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 229960002949 fluorouracil Drugs 0.000 description 7
- 238000011725 BALB/c mouse Methods 0.000 description 6
- 240000009138 Curcuma zedoaria Species 0.000 description 6
- 235000003405 Curcuma zedoaria Nutrition 0.000 description 6
- 239000001812 curcuma zedoaria berg. rosc. Substances 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 239000003053 toxin Substances 0.000 description 6
- 231100000765 toxin Toxicity 0.000 description 6
- 235000019509 white turmeric Nutrition 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 4
- 238000000465 moulding Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 206010000077 Abdominal mass Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 108700000707 bcl-2-Associated X Proteins 0.000 description 3
- 102000055102 bcl-2-Associated X Human genes 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000009736 wetting Methods 0.000 description 3
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- 102000003952 Caspase 3 Human genes 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100028843 DNA mismatch repair protein Mlh1 Human genes 0.000 description 2
- 102100034157 DNA mismatch repair protein Msh2 Human genes 0.000 description 2
- 102100021147 DNA mismatch repair protein Msh6 Human genes 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
- 101001134036 Homo sapiens DNA mismatch repair protein Msh2 Proteins 0.000 description 2
- 101000968658 Homo sapiens DNA mismatch repair protein Msh6 Proteins 0.000 description 2
- 208000006083 Hypokinesia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229910015837 MSH2 Inorganic materials 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000032818 Microsatellite Instability Diseases 0.000 description 2
- 108010074346 Mismatch Repair Endonuclease PMS2 Proteins 0.000 description 2
- 102100037480 Mismatch repair endonuclease PMS2 Human genes 0.000 description 2
- 108010026664 MutL Protein Homolog 1 Proteins 0.000 description 2
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 2
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 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 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- OPFTUNCRGUEPRZ-UHFFFAOYSA-N (+)-beta-Elemen Natural products CC(=C)C1CCC(C)(C=C)C(C(C)=C)C1 OPFTUNCRGUEPRZ-UHFFFAOYSA-N 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N (-)-beta-elemene Chemical compound CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000092665 Atractylodes macrocephala Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000218202 Coptis Species 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102100030708 GTPase KRas Human genes 0.000 description 1
- 102100039788 GTPase NRas Human genes 0.000 description 1
- 241000726221 Gemma Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 1
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 101000911513 Homo sapiens Uncharacterized protein FAM215A Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000233932 Sparganium Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 102100026728 Uncharacterized protein FAM215A Human genes 0.000 description 1
- ZSTCHQOKNUXHLZ-PIRIXANTSA-L [(1r,2r)-2-azanidylcyclohexyl]azanide;oxalate;pentyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate;platinum(4+) Chemical compound [Pt+4].[O-]C(=O)C([O-])=O.[NH-][C@@H]1CCCC[C@H]1[NH-].C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 ZSTCHQOKNUXHLZ-PIRIXANTSA-L 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 1
- 235000008207 calcium folinate Nutrition 0.000 description 1
- 239000011687 calcium folinate Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000003690 classically activated macrophage Anatomy 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000000547 effect on apoptosis Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 238000001565 modulated differential scanning calorimetry Methods 0.000 description 1
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000003903 pelvic floor Anatomy 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000003330 peritoneal dialysis fluid Substances 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000003456 pulmonary alveoli Anatomy 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
-
- 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
- A61K36/489—Sophora, e.g. necklacepod or mamani
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
-
- 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)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
- A61K36/8994—Coix (Job's tears)
-
- 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)
- A61K36/902—Sparganiaceae (Bur-reed 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)
- A61K36/9066—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
-
- 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, 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
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
-
- 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
-
- 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
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor, a preparation method and application thereof, wherein the traditional Chinese medicine composition takes hairyvein agrimony and coptis root which are mutually combined as monarch drugs, radix sophorae flavescentis, raw coix seed, vinegar-processed rhizoma sparganii and vinegar-processed rhizoma zedoariae as ministerial drugs, prepared astragalus root and bran-processed rhizoma atractylodis macrocephalae as adjuvant and guide drugs, and the drugs are combined to achieve the effects of removing blood stasis and detoxifying, clearing heat and resolving dampness, strengthening spleen and tonifying qi, has definite curative effects for treating microsatellite stabilized colorectal tumor, and has various effects of regulating and controlling proliferation/apoptosis of microsatellite stabilized colorectal tumor, inhibiting liver/lung metastasis and the like. The selected medicinal material has stable basic source, reliable quality, no toxic or side effect, flexible preparation form of the medicinal composition, and suitability for personalized administration of different courses of disease and medicament application groups; the preparation process is stable and controllable, is simple and convenient to operate, and is easy for large-scale preparation.
Description
Technical Field
The invention relates to a traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and a preparation method and application thereof, in particular to a traditional Chinese medicine composition for effectively treating microsatellite stabilized colorectal tumor by inhibiting tumor proliferation and metastasis and inducing tumor apoptosis and a preparation method and application thereof.
Background
Colorectal cancer is one of the common malignant tumors worldwide, and despite the improvement of prognosis of intestinal cancer patients by the application of therapies such as surgery, chemotherapy, targeting, immunotherapy and the like, the survival rate of advanced colorectal cancer patients for 5 years is still low.
Advanced colorectal cancer can be primarily classified into microsatellite instability (MSI-H) and low microsatellite instability/microsatellite stability (MSI-L/MSS), with MSI-H type colorectal cancer accounting for only a small proportion of advanced colorectal cancer patients for which immunotherapy is better; the main proportion of MSI-L/MSS colorectal cancer has no obvious curative effect on the colorectal cancer, and the chemotherapy has high treatment cost, large side effect and insignificant effect. Thus, there is still a lack of effective therapeutic drugs for a large number of microsatellite stabilized advanced colorectal cancer patients.
Disclosure of Invention
The invention aims to: aiming at the defects of poor curative effect of the existing medicine on microsatellite stabilized colorectal tumor and the like, the invention aims to provide a traditional Chinese medicine composition for effectively treating microsatellite stabilized colorectal tumor through various mechanisms, and a preparation method and application thereof.
The technical scheme is as follows: as a first aspect of the invention, the traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor comprises 9-15 parts of hairyvein agrimony, 2-8 parts of coptis chinensis, 6-12 parts of radix sophorae flavescentis, 9-15 parts of raw coix seed, 6-12 parts of rhizoma sparganii with vinegar, 6-12 parts of rhizoma curcumae with vinegar, 12-18 parts of radix astragali preparata and 9-15 parts of bighead atractylodes rhizome stir-fried with bran by weight.
Further, in the traditional Chinese medicine composition, the ratio of the hairyvein agrimony to the coptis chinensis is 2:1-3:1.
preferably, the traditional Chinese medicine composition comprises 12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of radix sophorae flavescentis, 12 parts of raw coix seed, 9 parts of rhizoma sparganii vinegar, 9 parts of rhizoma curcumae vinegar, 15 parts of radix astragali preparata and 12 parts of bighead atractylodes rhizome stir-fried with bran by weight.
The traditional Chinese medicine is a treasure of China and plays an important role in the treatment of malignant tumor. Although the name of malignant tumor is not recorded in ancient Chinese medical books, the clinical manifestations of diseases such as intestinal wind, visceral toxin, abdominal mass are similar to those of modern colorectal cancer from the clinical symptoms. The traditional Chinese medicine composition is applied to clinical diagnosis and treatment of malignant tumors by means of the theory of cancer toxin pathogenesis on the basis of the theory of cancer toxin, and achieves good clinical curative effects. Basic research shows that CD4 in MSS/MSI-L colorectal cancer + /CD8 + Infiltration of T lymphocyte and M1 macrophage is obviously reduced, anti-tumor activity is weakened, and cell infiltration of regulatory T cell (Treg), plasma cell and marrow-derived suppressor cell (MDSCs) is reducedThe wetting is significantly increased. Therefore, the method plays an integrated advantage of traditional Chinese medicine, and the multichannel comprehensive regulation of infiltration of immune cells in colorectal cancer microenvironment can be used for treating MSS/MSI-L colorectal cancer.
In the traditional Chinese medicine composition, the agrimony and the coptis chinensis (2:1-3:1) are compatible and are used as monarch drugs, the agrimony is named as 'Deli cao', has bitter and astringent taste, calms, returns to heart and liver channels, has the functions of stopping bleeding and stopping diarrhea, and simultaneously has the functions of detoxification and deficiency tonifying, and the 'materia medica outline' records that the agrimony has the efficacy of treating the abdominal mass and blood. Huang Lian is bitter and cold in nature, enters heart, liver and large intestine meridians, and has the actions of clearing heat and drying dampness, purging fire and removing toxin. The two are combined together, so that the Chinese medicinal composition has the effects of clearing heat, drying dampness, removing cancer toxin, regulating the growing microenvironment, eliminating evil without hurting body resistance. In the formula, the kuh-seng, the raw coix seed, the rhizoma sparganii and the rhizoma curcumae are taken as ministerial drugs, and the kuh-seng has bitter taste and cold property, can clear heat, remove dampness, kill parasites, promote urination and remove fire in small intestine; the raw coix seed is sweet and light in nature and taste, and plays roles of promoting diuresis, removing dampness, strengthening spleen, relieving diarrhea, removing arthralgia, expelling pus, detoxifying and resolving hard mass in a synergistic manner; is matched with kuh-seng to strengthen the functions of clearing heat and drying dampness, so that the environment generated by cancer toxin is not present; rhizoma Sparganii and Curcumae rhizoma are pungent and bitter in flavor, and have effects of removing blood stasis, promoting qi circulation, resolving food stagnation and relieving pain, both are prepared into decoction pieces with vinegar, vinegar rhizoma Sparganii has enhanced analgesic effect, and vinegar Curcumae rhizoma has increased blood breaking effect, and can be used for treating abdominal mass, and both are matched with monarch drug pair to strengthen anticancer and toxic substance removing effects. The baked astragalus root and the bran-fried atractylodes macrocephala are adjuvant drugs in the recipe, and both are sweet and warm in nature, enter lung and spleen meridians, have the effects of tonifying qi and middle-jiao, prevent the healthy qi from being damaged by the excessive attack on the vats, and the whole recipe has the effects of removing blood stasis and detoxifying, clearing heat and resolving dampness and tonifying spleen and qi together.
In the theory of traditional Chinese medicine, the principal drug is the drug with the first Chinese medicine liju and the main therapeutic effect on the main disease or the main syndrome. The traditional Chinese medicine composition is used for treating microsatellite stabilized colorectal cancer by combining hairyvein agrimony with coptis chinensis (2:1-3:1) as a monarch drug for the first time, and can be used for treating and controlling the development of the course of the disease, effectively relieving the illness state and obtaining good treatment effect.
As a second aspect of the present invention, the extract of the above-mentioned traditional Chinese medicine composition is added with a pharmaceutically acceptable carrier to prepare a pharmaceutical composition, and a specific preparation form comprises oral liquid, tablets, capsules, granules or suppositories. Wherein, the extract of the traditional Chinese medicine composition accounts for 20-30% by mass percent; the pharmaceutically acceptable carrier is selected from one or more of dextrin, lactose, starch, sucrose, glucose, microcrystalline cellulose, mannose, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, and aspartame.
As a third aspect of the present invention, the method for preparing the above pharmaceutical composition comprises the steps of:
(1) Preparing an extract
The method comprises the following steps: taking each medicinal decoction piece, hydrating and extracting twice, and combining the decoctions to obtain an extracting solution;
the second method is as follows: extracting raw coix seed, rhizoma sparganii, rhizoma curcumae, and rhizoma atractylodis macrocephalae decoction pieces by supercritical extraction to obtain an extract I, extracting residues and other medicinal decoction pieces by hydration twice, and mixing the decoctions to obtain an extract II;
(2) Preparing concentrated solution
Concentrating the extract II prepared by the first method or the extract II prepared by the second method in the step (1) to an extract with the relative density of 1.08-1.12 at 60 ℃, adding ethanol until the total volume percentage is 65-75%, precipitating with ethanol, and concentrating the filtrate to a concentrated solution with the relative density of 1.20-1.30 at 65 ℃;
(3) Preparation of pharmaceutical compositions
Adding a pharmaceutically acceptable carrier into the concentrated solution of the extracting solution prepared by the first method in the step (1);
or adding pharmaceutically acceptable carriers into the concentrated solutions of the extracting solutions I and II prepared by the method II in the step (1) respectively to prepare the pharmaceutical composition.
Wherein, the method of the two extractions in the step (1) is that the water which is 8-12 times of the weight of the medicinal materials is used for the first extraction, the soaking is carried out for 0.5h, and the decoction is carried out for 1-2h; extracting with 6-10 times of water, and decocting for 1-2 hr.
Further, the step (3) also comprises spray drying the concentrated solution, wherein the air inlet temperature of the spray drying is 100-120 ℃, the air outlet temperature is 80-90 ℃, the material temperature is 60-80 ℃, and the atomization pressure is 0.2-0.4MPa.
Specifically, the concentrated solution is added with water and auxiliary materials to be prepared into oral liquid, or the concentrated solution is sprayed and dried, and the auxiliary materials are added to be prepared into tablets, capsules, granules and suppositories.
As a fourth aspect of the present invention, the above-mentioned traditional Chinese medicine composition or pharmaceutical composition may be prepared into a medicament for treating microsatellite-stabilized colorectal cancer, and is specifically used for regulating proliferation or apoptosis of microsatellite-stabilized colorectal cancer and inhibiting liver metastasis or lung metastasis of microsatellite-stabilized colorectal cancer.
The beneficial effects are that: compared with the prior art, the invention has the following remarkable advantages:
1. the traditional Chinese medicine composition has reasonable prescription design and strict compatibility, the hairyvein agrimony and the coptis root are compatible with each other to be monarch drugs, the kuh-seng, the raw coix seed, the vinegar burreed tuber and the vinegar zedoary are used as ministerial drugs, the roasted astragalus root and the bran-fried bighead atractylodes rhizome are used as adjuvant drugs, and the drugs are combined to remove blood stasis and detoxify, clear heat and remove dampness, and invigorate the spleen and replenish qi, so that the traditional Chinese medicine composition has definite curative effect on treating microsatellite stabilized colorectal tumor, has various effects of regulating and controlling microsatellite stabilized colorectal tumor proliferation/apoptosis, inhibiting liver/lung metastasis and the like;
2. the medicinal materials are recorded in Chinese pharmacopoeia, the basic sources are stable, the quality is reliable, no toxic or side effect is caused, and the economy is good;
3. the preparation form of the pharmaceutical composition is flexible, and the pharmaceutical composition is suitable for personalized administration of different disease courses and drug administration crowds;
4. the preparation process is stable and controllable, is simple and convenient to operate, and is easy for large-scale preparation.
Drawings
FIG. 1 shows the inhibition effect of the Chinese medicinal composition of the present invention on tumor volume of tumor-bearing mice;
FIG. 2 shows the effect of the Chinese medicinal composition of the present invention on the expression of apoptosis proteins in colon cancer-bearing tumor tissue;
FIG. 3 is the effect of the traditional Chinese medicine composition of the present invention on colorectal cancer liver metastasis;
FIG. 4 is a HE staining observation (40X) of liver tissue;
FIG. 5 effect of important compositions of the invention on colorectal cancer lung metastasis;
FIG. 6 is a HE staining observation (40X) of lung tissue.
Detailed Description
The technical scheme of the invention is further described below by referring to examples.
Example 1
12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of kuh-seng, 12 parts of raw coix seed, 9 parts of vinegar burred tuber, 9 parts of vinegar zedoary, 15 parts of roasted astragalus root and 12 parts of bran-fried bighead atractylodes rhizome. Combining the medicinal materials, adding water for decoction twice, wherein the first time is 10 times of the weight of the medicinal materials, soaking for 0.5h, decocting for 1h, the second time is 8 times of the weight of the medicinal materials, decocting for 1h, combining the decoctions, concentrating under reduced pressure to relative density of 1.08 at the temperature of between 0.05MPa and 60 and 70 ℃, adding 95% (v/v) ethanol to ensure that the ethanol content reaches 75% (v/v), stirring, standing for 24 hours, recovering ethanol under reduced pressure and concentrating the filtrate, concentrating the filtrate under reduced pressure to relative density of 1.30 at the temperature of between 0.07MPa and 65 ℃, spray drying (provided that the air inlet temperature is 120 ℃, the material temperature is 80 ℃, the atomization pressure is 0.4MPa, the spray speed is 10 ml/s), adding starch, uniformly mixing, wetting with a proper amount of 80% (v/v) ethanol, granulating through a 20-mesh sieve, drying at the temperature of between 60 and 70 ℃, 60-mesh sieving, granulating, coating, packaging, and tabletting to obtain tablets.
Example 2
12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of kuh-seng, 12 parts of raw coix seed, 9 parts of vinegar burred tuber, 9 parts of vinegar zedoary, 15 parts of roasted astragalus root and 12 parts of bran-fried bighead atractylodes rhizome. Combining the medicinal materials, adding water for decoction twice, wherein the first time is 10 times of the weight of the medicinal materials, decocting for 1.5 hours, the second time is 8 times of the weight of the medicinal materials, decocting for 1.5 hours, combining the decoctions, concentrating under reduced pressure to 65 ℃ under 0.07MPa and 60-70 ℃ until the relative density is 1.15, adding 95% (v/v) ethanol to enable the alcohol content to reach 75% (v/v), stirring, standing for 24 hours, recovering ethanol under reduced pressure, concentrating the filtrate under reduced pressure to 65 ℃ under 0.07MPa and 65 ℃ until the relative density is 1.25, spray drying (wherein the air inlet temperature is 100 ℃, the air outlet temperature is 80 ℃, the material temperature is 70 ℃, the atomization pressure is 0.2MPa, the spray speed is 5 ml/s), adding dextrin and the like, granulating by a dry method, sieving with a 60-mesh sieve, and filling the filtrate into a No. 1 capsule to obtain the capsule.
Example 3
12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of kuh-seng, 12 parts of raw coix seed, 9 parts of vinegar burred tuber, 9 parts of vinegar zedoary, 15 parts of roasted astragalus root and 12 parts of bran-fried bighead atractylodes rhizome. Combining the medicinal materials, decocting with water twice, wherein the first time is 12 times of the weight of the medicinal materials, decocting for 2 hours, the second time is 10 times of the weight of the medicinal materials, decocting for 2 hours, combining the decoctions, concentrating under reduced pressure at 0.07MPa and 60-70 ℃ until the relative density is 1.15, adding 95% (v/v) ethanol to ensure that the ethanol content reaches 75% (v/v), stirring, standing for 24 hours, recovering and concentrating the filtrate under reduced pressure, concentrating the filtrate under reduced pressure at 0.07MPa and 65 ℃ until the relative density is 1.25, spray drying (provided that the inlet air temperature is 110 ℃, the outlet air temperature is 80 ℃, the material temperature is 65 ℃, the atomization pressure is 0.3MPa, the spray speed is 7.5 ml/s), adding proper lactose, wetting with a proper amount of 80% (v/v) ethanol, preparing soft materials, sieving with a 14-mesh sieve, granulating at 50-70 ℃, and drying at 60 meshes to obtain granules.
Example 4
12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of kuh-seng, 12 parts of raw coix seed, 9 parts of vinegar burred tuber, 9 parts of vinegar zedoary, 15 parts of roasted astragalus root and 12 parts of bran-fried bighead atractylodes rhizome. Combining the medicinal materials, adding water for decoction twice, wherein the first time is 10 times of the weight of the medicinal materials, decocting for 1.5 hours, the second time is 8 times of the weight of the medicinal materials, decocting for 1.5 hours, combining the decoctions, concentrating under reduced pressure at 0.07MPa and 60-70 ℃ until the relative density is 1.15 at 65 ℃, adding 95% (v/v) ethanol to ensure that the ethanol content reaches 75% (v/v), stirring, standing for 24 hours, recovering and concentrating the filtrate under reduced pressure, concentrating the filtrate under reduced pressure at 0.07MPa and 65 ℃ until the relative density is 1.25 at 65 ℃, and adding water and sucrose to prepare the oral liquid.
Example 5
Taking 12 parts of raw coix seed, 9 parts of vinegar burred tuber, 9 parts of vinegar zedoary, 12 parts of bran-fried bighead atractylodes rhizome and adopting supercritical CO 2 Mixing the residue with herba et Gemma Agrimoniae 12 parts, coptidis rhizoma 5 parts, radix Sophorae Flavescentis 9 parts, and radix astragali Preparata 15 parts, decocting with water twice, wherein the water is 10 times of the weight of the materials, decocting for 1.5 hr, and the water is 8 times of the weight of the materials, decocting for 1.5 hr, mixing decoctions, and concentrating under reduced pressure at 0.07MPa and 60-70deg.CConcentrating to relative density of 1.1 at 65deg.C, adding 95% (v/v) ethanol to ethanol content of 70% (v/v), stirring, standing for 24 hr, recovering ethanol from the filtrate under reduced pressure, concentrating under reduced pressure at 60deg.C under 0.08MPa to relative density of 1.3 at 60deg.C to obtain extract II, adding oily and water-soluble matrix, and hot melting to obtain suppository.
Example 6: regulation and control effect 1 of traditional Chinese medicine composition on proliferation and apoptosis of microsatellite stabilized colorectal cancer, animal modeling and administration
The mouse-derived microsatellite stabilized cell CT26 is cultured in RPMI-1640 medium (containing 10% fetal bovine serum, 100IU/mL penicillin and 100IU/mL streptomycin) and then left to stand at 37 ℃ and 5% CO 2 Culturing in a cell culture incubator. After digestion with trypsin, the microsatellite stabilized mouse colorectal cancer CT26 cells are collected, and the cell density is adjusted to 2X 10 by using pre-cooled physiological saline 6 And (3) inoculating the strain/mL subcutaneously to axilla of a BALB/c mouse, observing the tumor condition every other day by 0.2 mL/mouse, and touching the inoculation part of the mouse after the molding is finished to be the molding success standard. 56 BALB/c mice are all neoplastic, the neoplastic rate is 100%, the model mice are randomly divided into 7 groups according to weight layering, 8 mice in each group, and the low, medium and high dose groups of the traditional Chinese medicine composition are determined to be 6.5, 13 and 26 g.Kg according to the equivalent dose conversion method of human and animals -1 The dosage of the positive medicine elemene is 5 mg.Kg -1 And 5-fluorouracil (5-Fufluorouracil, 5-FU) (5mg.Kg) -1 Once every three days), the 5-FU group was administered by intraperitoneal injection, the remaining groups were administered by intragastric administration, the model group was given an equal volume of saline intragastric administration, the blank group was not intervened, and the administration was continued for 14 days.
2. Inhibition of tumor-bearing mice by Chinese medicinal composition
After the end of administration, mice were sacrificed, tumor tissues were removed, weighed, and tumor inhibition rates of the respective doses of the Chinese medicinal composition were calculated, and the results are shown in fig. 1 and table 1: compared with the model group, the average tumor weight of the traditional Chinese medicine composition administration group is reduced. Wherein, the weight of the low-dose group tumor of the traditional Chinese medicine composition is 0.74+/-0.24 g, and the tumor inhibition rate is 51.6%; the tumor weight of the medium-dose group is 0.75+/-0.31 g, and the tumor inhibition rate is 50.9%; the tumor weight of the high-dose group is 0.73+/-0.22 g, the tumor inhibition rate is 52.3 percent, and the high-dose group is obviously different from the model group which is 1.53+/-0.21 g (P < 0.05). The result shows that the traditional Chinese medicine composition can obviously inhibit the growth of tumors in colorectal cancer tumor-bearing mice.
TABLE 1 inhibition of tumor proliferation in tumor-bearing mice by Chinese medicinal compositionn＝8)
Note that: compared to the model group, 1) P <0.05,2) P <0.01,3) P <0.001, as follows.
3. Influence of traditional Chinese medicine composition on expression of apoptosis-related protein in tumor tissue of tumor-bearing mice
The Western blot method detects the influence of the Chinese medicinal composition on the expression of apoptosis proteins Bax and Bcl-2 and the levels of PARP and clear Caspase-3. As shown in the results of FIG. 2 and Table 2, compared with the control group, the Bax protein expression in the tumor-bearing tissue is up-regulated and the Bcl-2 protein expression is down-regulated after the traditional Chinese medicine composition is administered, so that the Bax/Bcl-2 ratio is remarkably increased. Meanwhile, as the administration concentration of the traditional Chinese medicine composition increases, the levels of PARP and clear caspase-3 protein also gradually increase, which shows that the traditional Chinese medicine composition has remarkable induction effect on apoptosis proteins.
TABLE 2 influence of Chinese medicinal composition on expression of apoptosis protein in tumor-bearing tissue of colon cancern＝3)
Example 7: inhibition of liver metastasis of microsatellite stabilized colorectal cancer by traditional Chinese medicine composition
1. Moulding method
(1) Cell culture
The mouse-derived microsatellite stabilized cell CT26 is cultured in RPMI-1640 medium (containing 10% fetal bovine serum, 100IU/mL penicillin and 100IU/mL streptomycin) and then left to stand at 37 ℃ and 5% CO 2 Culturing in a cell culture incubator.
(2) Colorectal cancer liver metastasis mouse model establishment and administration
Trypsin digestion, collection of cultured CT26 cells, adjustment of cell density to 2X 10 6 . BALB/c mice were anesthetized with sodium pentobarbital by intraperitoneal injection, the left back was exposed after the skin of the surgical field was sterilized, the spleen was exposed by beveling the 0.5-1.0cm incision, the lower spleen was lifted out of the abdominal cavity, 0.2mL cells per mouse were slowly injected into the spleen of the mice, hemostasis by compression was performed after the injection was completed, and extravasated cancer cells were wiped. The spleen was replaced and the abdomen was closed, and a colorectal cancer liver transfer model was established. The following day, the surgical mice were randomized by body weight into 4 groups: model group, high dose group of Chinese medicinal composition (26 g/Kg), low dose group of Chinese medicinal composition (13 g/Kg), 5-FU group (5 mg/Kg.3day), 8 of each group. 8 additional unmolded BALB/c mice were taken as normal control. The mice were continuously fed with the stomach for 21 days, and after the last administration for 2 hours, the eyeballs were taken out to take blood, the mice were sacrificed, peripheral blood and peritoneal lavage fluid were collected, and at the same time, the organs of the mice were taken out for subsequent experiments.
2. Experimental results
(1) Effect of Chinese medicinal composition on colorectal cancer liver metastasis
The effect of each dose of the composition on colorectal liver metastasis is shown in fig. 3, and the extracted liver metastases are counted, and compared with the blank control group, the number of nodules of the liver tumors in the low-concentration group and the high-concentration group of the composition is reduced, and the differences are significant (P <0.05, P < 0.01). The result shows that the traditional Chinese medicine composition can obviously inhibit colorectal cancer liver metastasis.
(2) Influence of traditional Chinese medicine composition on pathological morphology of liver metastasis
The liver tissue is taken after the mice are killed, the pathological condition is observed by HE staining, the result is shown in figure 4, the liver tissue of the control group has clear texture, compact and ordered cell arrangement and uniform density, the cell morphology of the model group is incomplete, the structure is destroyed, large-area transfer nodules appear, and the tumor tissue cells are closely arranged. The growth is vigorous. After the traditional Chinese medicine composition is adopted for drying, macroscopic metastatic tumors still exist at low concentration, the cell structure is still shrunken compared with that of a blank control group, the liver structure of a high-concentration traditional Chinese medicine composition and a 5-FU administration group mouse is relatively complete, a small amount of metastatic tumors exist, and the volume is obviously reduced. The traditional Chinese medicine composition has the effect of inhibiting liver metastasis of colorectal cancer of mice.
Example 8: inhibition of microsatellite stabilized colorectal cancer lung metastasis by traditional Chinese medicine composition
1. Moulding method
(1) Cell culture
The mouse-derived microsatellite stabilized cell CT26 is cultured in RPMI-1640 medium (containing 10% fetal bovine serum, 100IU/mL penicillin and 100IU/mL streptomycin) and then left to stand at 37 ℃ and 5% CO 2 Culturing in a cell culture incubator.
(2) Tumor-bearing mouse model establishment and drug administration
CT26 cells were collected after trypsinization, and the cell density was adjusted to 2X 10 with physiological saline 6 . BALB/c mouse tail was sterilized with 75% alcohol and each mouse was inoculated subcutaneously with 0.2mL of the cell suspension to prepare a mouse colon cancer metastasis model. The following day, mice were randomly divided into 3 groups by body weight: model group, chinese medicinal composition group (13 g/Kg), 5-Fu group (5 mg/Kg), 8 each. 8 additional unmolded BALB/c mice were taken as normal control. The mice were continuously fed with stomach for 30 days, 5-FU 5mg/Kg was fed into the abdominal cavity once every 2 days, and after the last 2 hours of feeding, the eyes were taken out to remove blood and the mice were sacrificed, and at the same time, the organs of the mice were taken out for subsequent experiments.
2. Experimental results
(1) Effect of Chinese medicinal composition on colorectal cancer lung metastasis
The effect of each dose of the Chinese medicinal composition on colorectal liver metastasis is shown in fig. 5, and the lung of the mice is taken and counted, so that the number of nodules and the size of the nodules of the lung tumor of the low-concentration Chinese medicinal composition group and the high-concentration Chinese medicinal composition group are reduced compared with the blank control group. The result shows that the traditional Chinese medicine composition can obviously inhibit colorectal cancer lung metastasis.
(2) Effect of Chinese medicinal composition on organ indexes of each group of colorectal cancer liver metastasis model
The effect of the traditional Chinese medicine composition on the viscera of each group of mice is detected, the result is shown in table 3, and after the traditional Chinese medicine composition is administered for 14 days, the traditional Chinese medicine composition has no obvious effect on the spleen index and thymus index of tumor-bearing mice, and the difference of various indexes is not obvious. The traditional Chinese medicine composition has no obvious toxic or side effect on the immune system of mice.
TABLE 3 influence of Chinese medicinal composition on organ coefficients of mice
(3) Influence of traditional Chinese medicine composition on pathological morphology of liver metastasis
The results of HE staining of lung tissue of mice are shown in fig. 6: the lung group of the blank control group has clear alveoli and uniform cell density, and a large number of metastatic tumors are aggregated in the lung of the mice of the model group to form nodules. After the traditional Chinese medicine composition is adopted for drying, macroscopic metastatic tumors still remain, but the number of nodules is obviously reduced, and the alveolus structure is relatively complete, so that the traditional Chinese medicine composition has an inhibition effect on lung metastasis of colorectal cancer.
Example 9: observation of clinical application of Chinese medicinal composition
Medical case 1: patient She Mou, male, 70 years old, patient found colon cancer at 31 days 3 months 2020 at local hospital enteroscopy, 3 days 4 months 2020 under endoluminal colonoscopy, post operative pathological stage T3N2M0, immunohistochemical outcome: MMR proteins MLH1, MSH2, MSH6 and PMS2 in cancer tissues are completely expressed, microsatellite is stable, patients visit a hospital in the 18 th 4 th year of 2020 and have frequent disease, the symptoms such as irregular stool are improved before the patients are treated by the traditional Chinese medicine composition, and the patients do not relapse after the patients regularly follow the treatment until the patients take the medicine.
Medical case 2: patient Xu Mou, female, 68 years old, patient underwent laparoscopic right half-colon radical resection at 12 months 11 days 2018, post-operative pathology: right-hand semi-colon ulcerative tubular papillary adenocarcinoma, mid-differentiation. Mesenteric (3/13) lymph nodes see metastatic carcinoma. The XELOX regimen was followed for two cycles at 1 month 04 and 1 month 28 of 2019. No obvious abnormality is seen in the 9 th and 17 th of 2020 enteroscopes, and the patients in the last several months check that CA199 and CEA are continuously rising, CT in 2021 and 3 rd and 15 th shows multiple nodules of pelvic cavity and pelvic floor peritoneum, and the possibility of metastasis is considered. Gene detection (2021, 3, 20 days, fuel): MMR proteins MLH1, MSH2, MSH6 and PMS2 in cancer tissues are expressed completely, microsatellite stabilized (MSS type) and BRAF, KRAS, NRAS wild type. An anti-tumor treatment is performed on the 4 th month and 10 th year of 2021, and the scheme is that the drug is erbitux, irinotecan, calcium folinate and 5-FU. The dose of chemotherapy is regulated downwards for obvious diarrhea for 5 months 2 days, 5 months 26 days, 6 months 21 days and 7 months 14 days. The patient can visit the hospital in 8 months of 2021 for 7 days, and has the advantages of obvious hypodynamia, obvious cold feeling, no abdominal pain and diarrhea, anorexia and general sleep. After sleeping, the patient is easy to wake, and the patient can relieve the bowels for 2 times/day, is not shaped and has normal urine. A wiry and slippery pulse, a purple and dark tongue with thin and yellow coating. Compared with the traditional Chinese medicine composition for treating symptoms such as post-treatment hypodynamia, the traditional Chinese medicine composition disclosed by the invention is better in treatment, and obvious discomfort is not seen.
Claims (7)
1. A traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor liver metastasis is characterized by comprising 12 parts of hairyvein agrimony, 5 parts of coptis chinensis, 9 parts of radix sophorae flavescentis, 12 parts of raw coix seed, 9 parts of rhizoma sparganii vinegar, 9 parts of rhizoma curcumae vinegar, 15 parts of radix astragali preparata and 12 parts of bighead atractylodes rhizome stir-fried with bran by weight.
2. A pharmaceutical composition comprising the extract of the traditional Chinese medicine composition of claim 1 and a pharmaceutically acceptable carrier, wherein the preparation form comprises oral liquid, tablets, capsules, granules or suppositories.
3. The pharmaceutical composition according to claim 2, wherein the extract comprises 20-30% by mass.
4. A process for the preparation of a pharmaceutical composition according to any one of claims 2 to 3, comprising the steps of:
(1) Preparing an extract
The method comprises the following steps: taking each medicinal decoction piece, hydrating and extracting twice, and combining the decoctions to obtain an extracting solution;
the second method is as follows: extracting raw coix seed, rhizoma sparganii, rhizoma curcumae, and rhizoma atractylodis macrocephalae decoction pieces by supercritical extraction to obtain an extract I, extracting residues and other medicinal decoction pieces by hydration twice, and mixing the decoctions to obtain an extract II;
(2) Preparing concentrated solution
Concentrating the extract II prepared by the first method or the extract II prepared by the second method in the step (1) to an extract with the relative density of 1.08-1.12 at 60 ℃, adding ethanol until the total volume percentage is 65-75%, precipitating with ethanol, and concentrating the filtrate to a concentrated solution with the relative density of 1.20-1.30 at 65 ℃;
(3) Preparation of pharmaceutical compositions
Adding a pharmaceutically acceptable carrier into the concentrated solution of the extracting solution prepared by the first method in the step (1);
or adding pharmaceutically acceptable carriers into the concentrated solutions of the extracting solutions I and II prepared by the method II in the step (1) respectively to prepare the pharmaceutical composition.
5. The preparation method according to claim 4, wherein the two extraction methods in the step (1) are respectively that the water which is 8-12 times of the weight of the medicinal materials is extracted for the first time, soaked for 0.5h and decocted for 1-2h; extracting with 6-10 times of water, and decocting for 1-2 hr.
6. The method according to claim 4, wherein the step (3) further comprises spray-drying the concentrated solution, wherein the spray-drying has an inlet air temperature of 100-120 ℃, an outlet air temperature of 80-90 ℃, a material temperature of 60-80 ℃ and an atomization pressure of 0.2-0.4MPa.
7. Use of a traditional Chinese medicine composition according to claim 1 or a pharmaceutical composition according to any one of claims 2-3 for the preparation of a medicament for the treatment of microsatellite stabilized colorectal tumor liver metastases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210598584.1A CN114949142B (en) | 2022-05-30 | 2022-05-30 | Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210598584.1A CN114949142B (en) | 2022-05-30 | 2022-05-30 | Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114949142A CN114949142A (en) | 2022-08-30 |
| CN114949142B true CN114949142B (en) | 2024-04-02 |
Family
ID=82958376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210598584.1A Active CN114949142B (en) | 2022-05-30 | 2022-05-30 | Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114949142B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562193A (en) * | 2004-03-24 | 2005-01-12 | 成都厚发科技开发有限公司 | Combination of medicinal preparation of having antivirus function |
| CN106390013A (en) * | 2016-09-28 | 2017-02-15 | 江苏省中医院 | Compound traditional Chinese medicine composition capable of inhibiting colorectal liver metastases as well as preparation method and application thereof |
| CN107551254A (en) * | 2017-10-31 | 2018-01-09 | 南京中医药大学 | A kind of Chinese medicine composition with preventing and treating Colon and rectum precancerous lesion and preparation method and application |
-
2022
- 2022-05-30 CN CN202210598584.1A patent/CN114949142B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562193A (en) * | 2004-03-24 | 2005-01-12 | 成都厚发科技开发有限公司 | Combination of medicinal preparation of having antivirus function |
| CN106390013A (en) * | 2016-09-28 | 2017-02-15 | 江苏省中医院 | Compound traditional Chinese medicine composition capable of inhibiting colorectal liver metastases as well as preparation method and application thereof |
| CN107551254A (en) * | 2017-10-31 | 2018-01-09 | 南京中医药大学 | A kind of Chinese medicine composition with preventing and treating Colon and rectum precancerous lesion and preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| 仙连解毒方对结直肠癌湿热瘀毒证 模型小鼠肠道细胞类型的影响;张钦畅 等;中医杂志;第63卷(第5期);461-467 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114949142A (en) | 2022-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101181529B (en) | Chinese medicine composition for curing tumor and preparation method thereof | |
| CN100490789C (en) | Enteric coated Chinese medicinal capsule for treating cancer and preparation method thereof | |
| CN102861284B (en) | Traditional Chinese medicine compound preparation for treating non-small cell lung cancer and preparation method thereof | |
| CN114949142B (en) | Traditional Chinese medicine composition for treating microsatellite stabilized colorectal tumor and preparation method thereof | |
| CN105902827A (en) | Traditional Chinese medicine composition for improving immunity of human body and preparation method thereof | |
| CN101011457A (en) | Traditional Chinese medicine composition with immunological enhancement function | |
| CN114949160B (en) | Traditional Chinese medicine composition for colorectal adenoma enteroscopy postoperative treatment | |
| CN112190681A (en) | Traditional Chinese medicine composition for treating ulcerative colitis and preparation method thereof | |
| CN103830262A (en) | Auxiliary drug used for treating cancer, and applications thereof | |
| CN103028028B (en) | Traditional Chinese medicine agent for treating primary hepatic carcinoma | |
| CN114869987B (en) | Traditional Chinese medicine composition for preventing liver cancer | |
| CN102000303B (en) | Compound traditional Chinese medicine preparation for suppressing tumors | |
| CN111298061B (en) | Traditional Chinese medicine composition for clearing heat and detoxicating, removing stasis and resolving masses and preparation method thereof | |
| CN108743796B (en) | Traditional Chinese medicine composition for treating lung cancer and application thereof | |
| CN101468060A (en) | Pharmaceutical composition | |
| CN105434533A (en) | Traditional Chinese medicine composition for treating liver cancer | |
| CN1559601A (en) | Medicine for treating benign and malignant tumours | |
| CN104398704A (en) | Traditional Chinese medicine composition for treating stomach cancer and preparation method thereof | |
| CN116549511A (en) | Application of Hirudo collateral-dredging preparation in preparation of antitumor drugs | |
| CN104758749A (en) | Traditional Chinese medicine composition for treating liver cancer | |
| CN115192662A (en) | Traditional Chinese medicine composition and medicine for treating tumors | |
| CN111686192A (en) | Combination preparation for treating lung cancer and application thereof | |
| CN100553662C (en) | A kind of antineoplastic Chinese medicine composition and preparation method thereof | |
| CN102631493B (en) | Health care composition | |
| CN102600244A (en) | Chinese medicinal granules for treating liver cancer and protecting liver functions, as well as preparation method and application |
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 |