CN105878489A - Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition - Google Patents
Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition Download PDFInfo
- Publication number
- CN105878489A CN105878489A CN201610090199.0A CN201610090199A CN105878489A CN 105878489 A CN105878489 A CN 105878489A CN 201610090199 A CN201610090199 A CN 201610090199A CN 105878489 A CN105878489 A CN 105878489A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- bulk drug
- rascal
- tumor angiogenesis
- rhapontici seu
- 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.)
- Granted
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 230000005747 tumor angiogenesis Effects 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 title abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 53
- 239000000052 vinegar Substances 0.000 claims abstract description 12
- 235000021419 vinegar Nutrition 0.000 claims abstract description 12
- 241001074093 Echinopsis Species 0.000 claims description 66
- 230000001629 suppression Effects 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 33
- 229940079593 drug Drugs 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 238000009835 boiling Methods 0.000 claims description 12
- 238000000605 extraction Methods 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000004614 tumor growth Effects 0.000 abstract 1
- 241000270666 Testudines Species 0.000 description 63
- 240000005250 Chrysanthemum indicum Species 0.000 description 55
- 235000018959 Chrysanthemum indicum Nutrition 0.000 description 55
- 230000000694 effects Effects 0.000 description 32
- 241000251468 Actinopterygii Species 0.000 description 23
- 230000000366 juvenile effect Effects 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 12
- 210000004204 blood vessel Anatomy 0.000 description 12
- 229950000578 vatalanib Drugs 0.000 description 12
- 210000000709 aorta Anatomy 0.000 description 10
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 7
- CSJAXRKDCCWCSJ-UHFFFAOYSA-N Echinopsine Chemical compound C1=CC=C2N(C)C=CC(=O)C2=C1 CSJAXRKDCCWCSJ-UHFFFAOYSA-N 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 206010007247 Carbuncle Diseases 0.000 description 5
- 241000252212 Danio rerio Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000004720 fertilization Effects 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- -1 sorbefacient Substances 0.000 description 4
- 241000723353 Chrysanthemum Species 0.000 description 3
- 235000007516 Chrysanthemum Nutrition 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 241001482311 Trionychidae Species 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000013642 negative control Chemical group 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 description 2
- 244000192528 Chrysanthemum parthenium Species 0.000 description 2
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 206010017553 Furuncle Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229940126678 chinese medicines Drugs 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000005485 electric heating Methods 0.000 description 2
- 235000008384 feverfew Nutrition 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000000643 oven drying Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 229940072040 tricaine Drugs 0.000 description 2
- FQZJYWMRQDKBQN-UHFFFAOYSA-N tricaine methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=CC([NH3+])=C1 FQZJYWMRQDKBQN-UHFFFAOYSA-N 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000131317 Capitulum Species 0.000 description 1
- 241000132570 Centaurea Species 0.000 description 1
- 239000003390 Chinese drug Substances 0.000 description 1
- 241001672694 Citrus reticulata Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010049077 Hernia pain Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000736919 Pelodiscus sinensis Species 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010068956 Respiratory tract inflammation Diseases 0.000 description 1
- 241001093501 Rutaceae Species 0.000 description 1
- 241000593989 Scardinius erythrophthalmus Species 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000006374 Uterine Cervicitis Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 208000019790 abdominal distention Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000002929 anti-fatigue Effects 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008323 cervicitis Diseases 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 208000003512 furunculosis Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 201000007227 lymph node tuberculosis Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 230000003821 menstrual periods Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/58—Reptiles
- A61K35/586—Turtles; Tortoises, e.g. terrapins
-
- 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
-
- 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
- A61K36/287—Chrysanthemum, e.g. daisy
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention belongs to the field of medicine, and in particular relates to a pharmaceutical composition for inhibiting tumor angiogenesis and a preparation method of the pharmaceutical composition. The pharmaceutical composition, which is prepared from such medicinal raw materials as uniflower swisscentaury root and pericarpium citri reticulatae viride or pericarpium citri reticulatae viride processed with vinegar, is used for inhibiting the tumor angiogenesis; the pharmaceutical composition is capable of effectively inhibiting tumor growth; and the pharmaceutical composition has a good medicinal value; therefore, a new choice is provided for clinical use.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of pharmaceutical composition suppressing tumor angiogenesis and preparation method.
Background technology
Angiogenesis (angiogenesis) is to germinate from existing blood vessel to generate the process of new blood vessel.This process is thin with blood vessel endothelium
Born of the same parents migrate relevant with propagation.Embryo development procedure is along with Angiogenesis.But except wound healing, female menstrual period and some pathology
Outward, seldom there is Angiogenesis to process (such as cancer) in adult.
Angiogenesis suffers from extremely important meaning to growth, transfer or even the prognosis of malignant entity tumor.Angiogenesis is to dislike
Property entity tumor break through after basement membrane of epithelium necessary to further growth.The blood vessel being newly formed in tumour has himself uniqueness
Design feature, shows as tube wall imperfect, without smooth muscle elements, is only made up of the basement membrane of porose endothelial cell and sheet.Many
Number scholar thinks, the design feature of new vessels makes malignant tumor tissue generation DISTANT METASTASES IN be possibly realized.Therefore, malignant entity
In tumour, new vessels is considered as quantitatively a kind of important independent prognostic marker.
Turtle shell is the carapace of Trionychidae animal soft-shelled turtle Trionyx sinensis Wiegmann.Nature and flavor are salty, cold.Nourishing and suppressing Yang, soft heavily fortified point dissipates
Knot, brings down a fever except steaming.For fever due to yin deficiency, the hot hectic fever due to yin of labor, endogenous deficient wind, through closing, lump in the abdomen, chronic malaria malaria is female.Usage and dosage is
9～24 grams.Modern medicine shows, the processed product of turtle shell has turtle shell and vinegar turtle shell two kinds.Modern study shows, turtle shell contains gelatine
Former (collagen), calcium carbonate, calcium phosphate, iodine etc..Turtle shell extract content is most with water extraction.Carapace is equal with plastron
11 kinds of elements such as calcic, phosphorus, sodium, magnesium, potassium, zinc, iron, manganese, cobalt, copper, arsenic.Pharmacological action is as follows:
1, strong effect: soft-shelled turtle polysaccharide 0.5,1.0,2.0g/kg gavage 15-20 days, mouse hypoxia-bearing capability and anti-can be significantly improved
Refrigeration, can extend mouse swimming time, have antifatigue effect.
2, immunologic enhancement: soft-shelled turtle polysaccharide 0.5,1.0,2.0g/kg gavage 15-20 days, mouse plaque test can be significantly improved thin
The haematolysis ability of born of the same parents, promotes that hemolytic antibody generates；And strengthen mouse delayed allergy.
3, antitumor action.It is inhibited to mouse transplanting solid carcinoma MH134 that Turtle Shell is administered orally 280mg/kg,
Making diameter of tumor reduce, tumor weight significantly alleviates.Ascites carcinoma is not then had remarkable effect.Nude mice to inoculation people's colon-cancer cell
Pressing 800mg/kg oral dose turtle's carapace powder every day, compare with control group after treatment 35d, tumour inhibiting rate is 92.15%, neoplasm necrosis
Area reaches 67%, compares with 5 FU 5 fluorouracil (5-Fu) group, and its advantage is not cause Penetration of Host Leucocytes number to decline, and shows turtle's carapace powder
Not only having inhibitory action to people's intestinal cancer, and side reaction is little, the suppression to marrow is light more than 5-Fu.
4, other: with 0.5% or 1.0% soft-shelled turtle polysaccharide Renger immersion bubble Toad Sciatic Nerve specimen-gastrocnemius muscle, have increase shrink height
Degree and picture line area, the effect of prolongation contracts last time.These product can suppress the hyperplasia of connective tissue, and can disappear caking；And have
There is the effect increasing plasma protein, can be used for the anaemia caused by hepatopathy.
Radix Rhapontici seu Radix Echinopsis is the dry root of feverfew centaurea monanthos Georgi.Bitter is cold in nature.Effect is clearing heat and detoxicating, and disappear carbuncle, lactogenesis, and relaxing muscles and tendons is promoted blood circulation.
Swell and ache for acute mastitis, ulcer carbuncle on the back, scrofula sore, alactation, arthritis with fixed pain caused by dampness contraction.Usage and dosage 5-9g.Modern study shows
Radix Rhapontici seu Radix Echinopsis pharmacological action is as follows:
1, the effect to central nervous system, the effect of echinopsine is similar to strychnine, low dose of to animal performance excitation,
Heavy dose then causes spasm, occurs that whole body suppresses later, and the mice sleep causing barbital has the effect of reviving, and can excited god
Through muscle device, promote perineural recovery process.
2, the impact on cardiovascular system, echinopsine can cause drop in blood pressure to anesthetized cat, and contractile force strengthens, to the in vitro frog
The heart can make heart shrink tension rise, and shrinkage amplitude weakens, and high concentration can make heart stop the systole phase, and the in vitro rabbit ear is showed blood vessel
Expansion.
3, other, echinopsine can make cat intestine in vitro tension force increase, then suppress rabbits infestines.
Rascal is rutaceae orange Citrus reticulata Blanco and the dry young fruit of variety or the fruit of immature fruit
Skin.Bitter, pungent, warm in nature.There is soothing the liver relieving stagnant Qi, effect that long-pendingization that disappear is stagnant.For distending pain in the chest and hypochondrium, hernia pain, breast addiction, breast
Carbuncle, stagnation of QI due to dyspepsia, abdominal distention.Usage and dosage 3～l0g.The processed product of rascal has rascal and stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar two kinds.
Mother chrysanthemum is the dry capitulum of feverfew mother chrysanthemum, cold nature, bitter, pungent.Effect is clearing heat and detoxicating, the flat liver of dispelling wind.
Swell for furunculosis carbuncle, red eye, swell pain, dizziness of having a headache.Usage and dosage 9-15g.Modern study shows, mother chrysanthemum can treat respiratory tract
Inflammation, cervicitis, carbuncle poison furuncle, flu, the infection of the upper respiratory tract etc..
Although it has been reported that turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum have antitumor action, but it is swollen not find that it has suppression
The effect that knurl new vessels generates.
Summary of the invention
First technical problem solved by the invention is to provide a kind of pharmaceutical composition suppressing tumor angiogenesis.
Pharmaceutical composition of the present invention is that weight proportion is as follows with Radix Rhapontici seu Radix Echinopsis and rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar as bulk drug:
Radix Rhapontici seu Radix Echinopsis 1-10 part, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 1-10 part；
Preferably, Radix Rhapontici seu Radix Echinopsis 2-8 part, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 2-8 part；
Most preferably, Radix Rhapontici seu Radix Echinopsis 5 parts, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 5 parts.
The present invention suppresses the pharmaceutical composition of tumor angiogenesis to be with Radix Rhapontici seu Radix Echinopsis, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar for primary raw material medicine, presses
According to pharmacy conventional method, add the medicament that pharmaceutically customary adjuvant is prepared from.
In technique scheme, described medicament is oral formulations or injection.Inputted by oral, intramuscular injection, vein
Or the mode such as lumbar injection is administered.
In technique scheme, described oral formulations is water decoction, powder, granule, capsule, tablet, oral liquid, conjunction
Agent or syrup.
In technique scheme, described customary adjuvant include the conventional diluent of pharmaceutical field, excipient, filler, adhesive,
Wetting agent, disintegrant, sorbefacient, surfactant, absorption carrier, lubricant etc..
Second technical problem solved by the invention is to provide described in technique scheme the medicine suppressing tumor angiogenesis
The preparation method of compositions, comprises the steps:
Method one: each bulk drug is ground into fine powder, mixing powder；Or
Method two: each bulk drug is ground into fine powder, encapsulated capsule；Or
Method three: each bulk drug is ground into fine powder, compressing tablet i.e. piece agent；Or
Method four: after each bulk drug water boiling and extraction, filter to obtain decoction liquor；Or
Method five: after each bulk drug water boiling and extraction, filter to obtain decoction liquor, is dried decoction liquor；Or
Method six: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, granule；Or
Method seven: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, encapsulated capsule；Or
Method eight: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, compressing tablet i.e. piece agent；Or
Method nine: after each bulk drug water boiling and extraction, makes water decoction, or add customary adjuvant make oral liquid, syrup,
Mixture.
In technique scheme, described in method five, the dry decoction liquor of institute is less than 5% to water content.
Concrete can make oral formulations or injection, the customary adjuvant that can add include the conventional diluent of pharmaceutical field,
Excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption carrier, lubricant
Deng.
To sum up, the present invention suppresses the pharmaceutical composition of tumor angiogenesis evident in efficacy, safety non-toxic, swollen for clinic suppression
Knurl new vessels generates and treatment tumour provides a kind of brand-new selection.
Accompanying drawing explanation
The juvenile fish light microscopic figure that Fig. 1 turtle shell is intervened
The juvenile fish fluorescence microscope display figure that Fig. 2 turtle shell is intervened
The juvenile fish aorta dorsalis fluorescence microscope display figure that Fig. 3 turtle shell is intervened
The juvenile fish light microscopic figure that Fig. 4 rascal is intervened
The juvenile fish fluorescence microscope display figure that Fig. 5 rascal is intervened
The juvenile fish aorta dorsalis fluorescence microscope display figure that Fig. 6 rascal is intervened
The juvenile fish light microscopic figure that Fig. 7 mother chrysanthemum is intervened
The juvenile fish fluorescence microscope display figure that Fig. 8 mother chrysanthemum is intervened
The juvenile fish aorta dorsalis fluorescence microscope display figure that Fig. 9 mother chrysanthemum is intervened
The juvenile fish light microscopic figure that Figure 10 Radix Rhapontici seu Radix Echinopsis is intervened
The juvenile fish fluorescence microscope display figure that Figure 11 Radix Rhapontici seu Radix Echinopsis is intervened
The juvenile fish aorta dorsalis fluorescence microscope display figure that Figure 12 Radix Rhapontici seu Radix Echinopsis is intervened
The juvenile fish light microscopic figure that Figure 13 positive control-PTK787 intervenes
The juvenile fish fluorescence microscope display figure that Figure 14 positive control-PTK787 intervenes
The juvenile fish aorta dorsalis fluorescence microscope display figure that Figure 15 positive control-PTK787 intervenes
The juvenile fish light microscopic figure that Figure 16 negative control-Vehicle Control (0.1%DMSO) intervenes
The juvenile fish fluorescence microscope display figure that Figure 17 negative control-Vehicle Control (0.1%DMSO) intervenes
The juvenile fish aorta dorsalis fluorescence microscope display figure that Figure 18 negative control-Vehicle Control (0.1%DMSO) intervenes
Detailed description of the invention
Experimental technique described in following embodiment, if no special instructions, is conventional method；Described reagent and material, as without special
Different explanation, the most commercially obtains.
One, investigation turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum suppression tumor angiogenesis test as follows:
1. materials and methods
1.1 material
Chinese medicine is purchased from Sichuan return of spring hall Pharmaceuticals Ltd.All reagent be purchased from Sigma-Aldrich Co. (St.Louis,
MO), PTK787 (vatalanib) is purchased from Selleckchem.Fli1a-EGFP transgenic zebrafish is used to test.Zebra fish
Raise according to standard environment.
1.2 preparation of reagents
Weigh Chinese medicine 450g, 8 times amount soak by water 3 times, each 1 hour, 3 decocting liquid are incorporated on 800W electric furnace dense
It is reduced to about 400ml, after crossing 100 eye mesh screens (filter residue keeps sample), is spread evenly across in evaporating dish, evaporating dish is placed in electric heating drum
In wind drying box, it is interrupted at 60 DEG C after being dried 62 hours, continues at drying at room temperature in glass desicator until making moisture and containing
Amount < the medicinal extract of 5% (oven drying method mensuration).
1.3 experimentation
The after fertilization embryo of 22 hours is put into (30, every hole embryo) in 12 orifice plates, use Chinese medicine to intervene 26 hours.Middle liquid medicine carries
Thing is dissolved in 0.1% dimethyl sulfoxide (DMSO), and it is 200 μ g/ml that every hole adds water extract of TCM concentration.Positive controls is
5 μ g/ml PTK787 (PTK787 vatalanib, a kind of vascular endothelial growth factor receptor antagonist), negative control group is 0.1%
DMSO.After fertilization 48 hours, tricaine anesthesia juvenile fish, use Nikon SMZ 1500 fluorescence microscopy to take pictures.Internode
Vascularization is the leading indicator evaluating traditional Chinese medicine effect.Also evaluate the toxicity of traditional Chinese medicine simultaneously.
1.4 results and conclusion
Use the juvenile fish light microscopic that turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum, positive control-PTK787, positive control-PTK787 intervene
Figure, fluorescence microscope display figure, aorta dorsalis fluorescence microscope display figure are shown in Fig. 1-18 respectively.
30 juvenile fish that all employing turtle shells, Radix Rhapontici seu Radix Echinopsis, rascal, 4 kinds of Chinese medicines of mother chrysanthemum and PTK787 intervene all occur in that blood vessel is raw
The defect become.Light microscopic and fluorescence microscope show, compare with 0.1%DMSO negative control, use turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal,
The juvenile fish that 4 kinds of Chinese medicines of mother chrysanthemum are intervened, defines less complete intersegmental blood vessel.High power lens shows, is merely able to observe once in a while
Aorta dorsalis seedling.5 μ g/ml PTK787 positive controls then can completely inhibit intersegmental blood vessel and back longitudinal direction blood vessel.Chinese medicine is not led
Cause zebra fish death or teratogenesis.Do not find neurotoxicity or the organ toxicity of Chinese medicine.
Two, investigation turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum combination application suppression tumor angiogenesis test as follows:
1. materials and methods
1.1 material
Chinese medicine turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum are purchased from Sichuan return of spring hall Pharmaceuticals Ltd.All reagent are purchased from
Sigma-Aldrich Co.(St.Louis,MO).Fli1a-EGFP transgenic zebrafish is used to test.Zebra fish is according to standard
Environment is raised.
1.2 preparation of reagents
Weigh Chinese medicine 500g, 8 times amount soak by water 3 times, each 1 hour, 3 decocting liquid are incorporated on 800W electric furnace dense
It is reduced to about 400ml, after crossing 100 eye mesh screens (filter residue keeps sample), is spread evenly across in evaporating dish, evaporating dish is placed in electric heating drum
In wind drying box, it is interrupted at 60 DEG C after being dried 62 hours, continues at drying at room temperature in glass desicator until making moisture and containing
Amount < the medicinal extract of 5% (oven drying method mensuration).
Wherein, when Chinese medicine is single application, then turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum respectively weigh 500g；Chinese medicine is combination of two
During application, then turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum respectively weigh 250g, are then used in mixed way according to compatibility；Chinese medicine is three's group
When closing application, then turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum respectively weigh 167g, are then used in mixed way according to compatibility；Chinese medicine is four
During combination application, then turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum respectively weigh 125g and are used in mixed way.
1.3 experimentation
The after fertilization embryo of 22 hours is put into (30, every hole embryo) in 12 orifice plates, use Chinese medicine to intervene 26 hours.Middle liquid medicine carries
Thing is dissolved in 0.1% dimethyl sulfoxide (DMSO), and it is 200 μ g/ml that every hole adds water extract of TCM concentration.After fertilization 48 hours,
Tricaine anesthesia juvenile fish, uses Nikon SMZ 1500 fluorescence microscopy to take pictures.Complete intersegmental blood vessel quantity and inhibiting rate
It it is the leading indicator evaluating traditional Chinese medicine effect.Count the quantity of complete intersegmental blood vessel (ISV), it may be assumed that connect aorta dorsalis (dorsal
Aorta, DA) to the number of intersegmental blood vessel of the longitudinal vein anastomosis of the back of the body (dorsal longitudinal anastomotic vessel, DLAV)
Amount.Data result represents with mean (minimum of a value, maximum).Inhibiting rate calculates according to below equation:
Inhibiting rate (%)=(1 ISVThe quantity of Chinese drug-treated group/ISVThe quantity of negative control group)×100。
1.4 results are as follows:
1.4.1 combination of two the results are shown in Table 1-6:
The quantitative comparison of table 1 Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum suppression new vessels
Result above understands, and the effect of Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum combination suppression new vessels compares with Radix Rhapontici seu Radix Echinopsis, and statistically significant is the most aobvious
Write difference (P < 0.01)；Comparing with mother chrysanthemum, although difference is not statistically significant, but inhibiting rate still increases.
The quantitative comparison of table 2 Radix Rhapontici seu Radix Echinopsis+rascal suppression new vessels
Result above understands, and the effect of Radix Rhapontici seu Radix Echinopsis+rascal combination suppression new vessels compares with Radix Rhapontici seu Radix Echinopsis, and statistically significant is the most notable
Difference (P < 0.01)；Compare with rascal, statistically significant pole significant difference (P < 0.001).
The quantitative comparison of table 3 mother chrysanthemums+rascal suppression new vessels
Result above understands, and the effect of mother chrysanthemum+rascal combination suppression new vessels compares with mother chrysanthemum, statistically significant pole
Significant difference (P < 0.01)；Compare with rascal, statistically significant pole significant difference (P < 0.001).
The quantitative comparison of table 4 turtle shells+mother chrysanthemum suppression new vessels
Result above understands, and the effect of turtle shell+mother chrysanthemum combination suppression new vessels compares with turtle shell, and statistically significant is the most aobvious
Write difference (P < 0.01)；Comparing with mother chrysanthemum, although difference is not statistically significant, but inhibiting rate still increases.
The quantitative comparison of table 5 turtle shells+Radix Rhapontici seu Radix Echinopsis suppression new vessels
Result above understands, and the effect of turtle shell+Radix Rhapontici seu Radix Echinopsis combination suppression new vessels compares with turtle shell, and statistically significant is the most notable
Difference (P < 0.01)；Compare with Radix Rhapontici seu Radix Echinopsis, statistically significant pole significant difference (P < 0.001).
The quantitative comparison of table 6 turtle shells+rascal suppression new vessels
Result above understands, and the effect of turtle shell+rascal combination suppression new vessels compares with turtle shell, and statistically significant is the most notable
Difference (P < 0.01)；Compare with rascal, statistically significant pole significant difference (P < 0.001).
1.4.2 three's combined result is shown in Table 7-10:
The quantitative comparison of table 7 Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal suppression new vessels
Result above understands, and Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal combines the effect suppressing new vessels and is used alone Radix Rhapontici seu Radix Echinopsis, rascal, open country
Chrysanthemum compares, statistically significant pole significant difference (P < 0.01).The effect of Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal combination suppression new vessels
Fruit is compared with Radix Rhapontici seu Radix Echinopsis+rascal, statistically significant pole significant difference (P < 0.01)；Compare with Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum, have statistics
The significant difference (P < 0.05) of meaning；Comparing with mother chrysanthemum+rascal, although difference is not statistically significant, but inhibiting rate is still
Slightly improve.
The quantitative comparison of table 8 mother chrysanthemums+turtle shell+rascal suppression new vessels
Result above understands, and mother chrysanthemum+turtle shell+rascal combines the effect suppressing new vessels and is used alone turtle shell, rascal, open country
Chrysanthemum compares, statistically significant pole significant difference (P < 0.01).The effect of mother chrysanthemum+turtle shell+rascal combination suppression new vessels
Fruit is compared with turtle shell+rascal, statistically significant pole significant difference (P < 0.01)；Compare with mother chrysanthemum+turtle shell, have statistics
The significant difference (P < 0.05) of meaning；Comparing with mother chrysanthemum+rascal, although difference is not statistically significant, but inhibiting rate is still
Slightly improve.
The quantitative comparison of table 9 mother chrysanthemums+turtle shell+Radix Rhapontici seu Radix Echinopsis suppression new vessels
Result above understands, and mother chrysanthemum+turtle shell+Radix Rhapontici seu Radix Echinopsis combines the effect suppressing new vessels and is used alone turtle shell, Radix Rhapontici seu Radix Echinopsis compares,
Statistically significant pole significant difference (P < 0.01)；Statistically significant significant difference is compared with being used alone mother chrysanthemum
(P<0.05).The effect of mother chrysanthemum+turtle shell+Radix Rhapontici seu Radix Echinopsis combination suppression new vessels compares with turtle shell+Radix Rhapontici seu Radix Echinopsis, and statistically significant is aobvious
Write difference (P < 0.05)；With mother chrysanthemum+turtle shell, mother chrysanthemum+Radix Rhapontici seu Radix Echinopsis compares, although difference is not statistically significant, but suppression
Rate the most slightly improves.
The quantitative comparison of table 10 turtle shells+rascal+Radix Rhapontici seu Radix Echinopsis suppression new vessels
Result above understands, and turtle shell+rascal+Radix Rhapontici seu Radix Echinopsis combines the effect suppressing new vessels and is used alone turtle shell, rascal, Radix Rhapontici seu Radix Echinopsis
Relatively, statistically significant pole significant difference (P < 0.01).The effect of turtle shell+rascal+Radix Rhapontici seu Radix Echinopsis combination suppression new vessels is with blue or green
Skin+Radix Rhapontici seu Radix Echinopsis compares, statistically significant pole significant difference (P < 0.01)；Comparing with turtle shell+Radix Rhapontici seu Radix Echinopsis, statistically significant is aobvious
Write difference (P < 0.05)；Comparing with turtle shell+rascal, although difference is not statistically significant, but inhibiting rate the most slightly improves.
1.4.3 four combined result are shown in Table 11:
The quantitative result of table 11 turtle shells+Radix Rhapontici seu Radix Echinopsis+rascal+mother chrysanthemum suppression new vessels
Result above understands:
1) effect of Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal+turtle shell combination suppression new vessels is relatively used alone turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, open country
Chrysanthemum compares, statistically significant pole significant difference (P < 0.01).
2) effect of Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal+turtle shell combination suppression new vessels is with turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum two-by-two
The composition of combination compares: with Radix Rhapontici seu Radix Echinopsis+rascal, Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum, turtle shell+mother chrysanthemum, turtle shell+rascal, turtle shell+Radix Rhapontici seu Radix Echinopsis ratio
Relatively, statistically significant pole significant difference (P < 0.01)；Compare with mother chrysanthemum+rascal, although difference is not statistically significant,
But inhibiting rate the most slightly improves.
3) effect of Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal+turtle shell combination suppression new vessels is with turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum two-by-two
The composition of combination compares: with mother chrysanthemum+turtle shell+Radix Rhapontici seu Radix Echinopsis, turtle shell+rascal+Radix Rhapontici seu Radix Echinopsis compares, statistically significant significant difference
(P<0.05)；With mother chrysanthemum+turtle shell+rascal, Radix Rhapontici seu Radix Echinopsis+mother chrysanthemum+rascal compares, although difference is not statistically significant, but
Inhibiting rate the most slightly improves.
To sum up, the present invention uses turtle shell, Radix Rhapontici seu Radix Echinopsis, rascal, mother chrysanthemum both can be used as medicine with folk prescription, it is also possible to compatibility is used as medicine, and
There is not incompatibility when using yet in compatibility, notable in terms of suppression tumor angiogenesis effect, new for clinic suppression tumour
Angiogenic generates and treatment tumour provides a kind of brand-new selection.
Claims (8)
1. suppress the pharmaceutical composition of tumor angiogenesis, it is characterised in that: it is made up of the bulk drug of following weight proportion:
Radix Rhapontici seu Radix Echinopsis 1-10 part, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 1-10 part.
The pharmaceutical composition of suppression tumor angiogenesis the most according to claim 1, it is characterised in that: by weighing as follows
The bulk drug composition of amount proportioning:
Radix Rhapontici seu Radix Echinopsis 2-8 part, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 2-8 part.
The pharmaceutical composition of suppression tumor angiogenesis the most according to claim 2, it is characterised in that: by weighing as follows
The bulk drug composition of amount proportioning:
Radix Rhapontici seu Radix Echinopsis 5 parts, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 5 parts.
4. according to the pharmaceutical composition of the suppression tumor angiogenesis described in any one of claim 1-3, it is characterised in that:
It is with Radix Rhapontici seu Radix Echinopsis, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar as bulk drug, according to pharmacy conventional method, adds what pharmaceutically customary adjuvant was prepared from
Medicament.
The pharmaceutical composition of suppression tumor angiogenesis the most according to claim 4, it is characterised in that: described medicine
Agent is oral formulations or injection.
The pharmaceutical composition of suppression tumor angiogenesis the most according to claim 5, it is characterised in that: described oral
Preparation is water decoction, powder, granule, capsule, tablet, oral liquid, mixture or syrup.
7. the preparation method of the pharmaceutical composition of the suppression tumor angiogenesis described in any one of claim 1-3, its feature
It is: comprise the steps:
Method one: each bulk drug is ground into fine powder, mixing powder；Or
Method two: each bulk drug is ground into fine powder, encapsulated capsule；Or
Method three: each bulk drug is ground into fine powder, compressing tablet i.e. piece agent；Or
Method four: after each bulk drug water boiling and extraction, filter to obtain decoction liquor；Or
Method five: after each bulk drug water boiling and extraction, filter to obtain decoction liquor, is dried decoction liquor；Or
Method six: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, granule；Or
Method seven: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, encapsulated capsule；Or
Method eight: after each bulk drug water boiling and extraction, concentrated extracting solution makes particle, compressing tablet i.e. piece agent；Or
Method nine: after each bulk drug water boiling and extraction, makes water decoction, or add customary adjuvant make oral liquid, syrup,
Mixture.
The preparation method of the pharmaceutical composition of suppression tumor angiogenesis the most according to claim 7, it is characterised in that:
Described in method five, the dry decoction liquor of institute is less than 5% to water content.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015100854139 | 2015-02-17 | ||
| CN201510085413 | 2015-02-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105878489A true CN105878489A (en) | 2016-08-24 |
| CN105878489B CN105878489B (en) | 2020-01-14 |
Family
ID=57014190
Family Applications (10)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510128977.6A Pending CN106138152A (en) | 2015-02-17 | 2015-03-23 | The new application of Flos Chrysanthemi Indici |
| CN201510127617.4A Pending CN106138144A (en) | 2015-02-17 | 2015-03-23 | The new application of Radix Rhapontici seu Radix Echinopsis |
| CN201510127428.7A Pending CN106138102A (en) | 2015-02-17 | 2015-03-23 | The new application of turtle shell |
| CN201510127586.2A Pending CN106138344A (en) | 2015-02-17 | 2015-03-23 | The new application of rascal |
| CN201610090382.0A Pending CN105878326A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
| CN201610090199.0A Expired - Fee Related CN105878489B (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method thereof |
| CN201610090202.9A Pending CN105878321A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
| CN201610089303.4A Pending CN105878325A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
| CN201610090372.7A Expired - Fee Related CN105878490B (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method thereof |
| CN201610090180.6A Pending CN105878488A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
Family Applications Before (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510128977.6A Pending CN106138152A (en) | 2015-02-17 | 2015-03-23 | The new application of Flos Chrysanthemi Indici |
| CN201510127617.4A Pending CN106138144A (en) | 2015-02-17 | 2015-03-23 | The new application of Radix Rhapontici seu Radix Echinopsis |
| CN201510127428.7A Pending CN106138102A (en) | 2015-02-17 | 2015-03-23 | The new application of turtle shell |
| CN201510127586.2A Pending CN106138344A (en) | 2015-02-17 | 2015-03-23 | The new application of rascal |
| CN201610090382.0A Pending CN105878326A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610090202.9A Pending CN105878321A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
| CN201610089303.4A Pending CN105878325A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
| CN201610090372.7A Expired - Fee Related CN105878490B (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method thereof |
| CN201610090180.6A Pending CN105878488A (en) | 2015-02-17 | 2016-02-17 | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (10) | CN106138152A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619760A (en) * | 2017-01-12 | 2017-05-10 | 茂县羌寨农副土特产品开发有限公司 | New applications of acanthopanax giraldii harms leaves |
| CN107281464A (en) * | 2017-07-05 | 2017-10-24 | 广州中医药大学 | A kind of pharmaceutical composition for treating tumour |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449812A (en) * | 2003-04-23 | 2003-10-22 | 李健勇 | Compound Chinese medicine for treating extensive cancer |
| CN102716423A (en) * | 2012-06-21 | 2012-10-10 | 刘坤 | Ruhesanjie capsule used for curing mammary hyperplasia diseases of women and preparation method thereof |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1223129A (en) * | 1998-01-14 | 1999-07-21 | 胡安黎 | Medicine cauterization and decoction for curing cancer and preparation process |
| CN1166378C (en) * | 2000-11-25 | 2004-09-15 | 赵香花 | 'Tongyuhuazhi' pill |
| CN1251756C (en) * | 2001-12-04 | 2006-04-19 | 何文法 | Series Chinese medicinal composition for treating tumor |
| CN1679908A (en) * | 2005-02-02 | 2005-10-12 | 王庆正 | Chinese medicine for treating tumor and preparation thereof |
| CN101073587B (en) * | 2006-05-18 | 2012-07-04 | 天津天士力制药股份有限公司 | Method for separating and extracting Chinese Thorowax Root |
| CN100444889C (en) * | 2007-01-10 | 2008-12-24 | 河南太龙药业股份有限公司 | Chinese medicinal composition for treating mastopathy |
| CN101049484A (en) * | 2007-05-14 | 2007-10-10 | 郝来勤 | Strong effective Chinese traditional medicine for treating lung cancer and other various cancers |
| CN101648002B (en) * | 2008-08-13 | 2013-12-25 | 北京和润创新医药科技发展有限公司 | Medicinal composition for treating skin injury and ulcer and application thereof |
| CN101670056B (en) * | 2008-09-10 | 2011-08-03 | 吴昆仑 | Medicament for treating malignant tumor |
| CN101612360B (en) * | 2009-07-17 | 2010-07-21 | 肖嘉惠 | Medicine for treating hepatitis, hepatocirrhosis and liver cancer |
| CN101934025B (en) * | 2010-08-18 | 2011-11-30 | 赵全会 | Traditional Chinese medicine for clearing away heat and toxic material |
| CN102370939A (en) * | 2010-08-18 | 2012-03-14 | 郑国红 | Body resistance-strengthening and anticancer traditional Chinese medicine |
| CN102090819A (en) * | 2010-09-08 | 2011-06-15 | 成进学 | Far infrared anti-electromagnetic wave body-perfuming sleeping bag used for teenagers, comprising nano selenium and traditional Chinese medicinal materials and capable of generating negative ions |
| CN102178796B (en) * | 2011-04-29 | 2013-02-27 | 苏州中药研究所 | Application of effective component of medulla Junci in preparing medicine, health food or cosmetic for resisting tumor or inhibiting angiogenesis |
| CN103099981B (en) * | 2013-02-09 | 2014-02-19 | 滨州职业学院 | Preparation method of traditional Chinese medicine for treating blepharitis marginalis caused by large moist heat |
| CN103230556B (en) * | 2013-05-15 | 2015-09-09 | 周富贵 | A kind of Chinese medicine and preparation method thereof for the treatment of liver cirrhosis, hepatocarcinoma |
| CN103655547A (en) * | 2013-12-18 | 2014-03-26 | 成都中医药大学 | Novel application of scutellarein |
| CN103920090A (en) * | 2014-03-19 | 2014-07-16 | 罗金 | Adnexal cyst treatment traditional Chinese medicine composition |
| CN104055978B (en) * | 2014-04-03 | 2018-03-20 | 刘黎霞 | Treat the Chinese medicine of hyperlipemia |
| CN105816643A (en) * | 2015-01-04 | 2016-08-03 | 扬子江药业集团上海海尼药业有限公司 | Application of traditional Chinese medicine composition for preventing and treating thyroid nodules |
-
2015
- 2015-03-23 CN CN201510128977.6A patent/CN106138152A/en active Pending
- 2015-03-23 CN CN201510127617.4A patent/CN106138144A/en active Pending
- 2015-03-23 CN CN201510127428.7A patent/CN106138102A/en active Pending
- 2015-03-23 CN CN201510127586.2A patent/CN106138344A/en active Pending
-
2016
- 2016-02-17 CN CN201610090382.0A patent/CN105878326A/en active Pending
- 2016-02-17 CN CN201610090199.0A patent/CN105878489B/en not_active Expired - Fee Related
- 2016-02-17 CN CN201610090202.9A patent/CN105878321A/en active Pending
- 2016-02-17 CN CN201610089303.4A patent/CN105878325A/en active Pending
- 2016-02-17 CN CN201610090372.7A patent/CN105878490B/en not_active Expired - Fee Related
- 2016-02-17 CN CN201610090180.6A patent/CN105878488A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449812A (en) * | 2003-04-23 | 2003-10-22 | 李健勇 | Compound Chinese medicine for treating extensive cancer |
| CN102716423A (en) * | 2012-06-21 | 2012-10-10 | 刘坤 | Ruhesanjie capsule used for curing mammary hyperplasia diseases of women and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105878489B (en) | 2020-01-14 |
| CN106138344A (en) | 2016-11-23 |
| CN105878321A (en) | 2016-08-24 |
| CN105878325A (en) | 2016-08-24 |
| CN105878326A (en) | 2016-08-24 |
| CN105878488A (en) | 2016-08-24 |
| CN106138102A (en) | 2016-11-23 |
| CN106138152A (en) | 2016-11-23 |
| CN106138144A (en) | 2016-11-23 |
| CN105878490A (en) | 2016-08-24 |
| CN105878490B (en) | 2019-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103495187A (en) | Type-B ultrasonic traditional Chinese medicinal gastroenterography assistant and method for preparing same | |
| CN105878489A (en) | Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method of pharmaceutical composition | |
| CN103251822B (en) | Qi-tonifying and dizziness-relieving Chinese medicine preparation for treating ischemic stroke, coronary disease and angina | |
| CN101697989B (en) | Application of notoginseng and extract thereof in preparing medicaments for treating and/or preventing coronary artherosclerosis | |
| WO2021169682A1 (en) | Traditional chinese medicine composition, and preparation method therefor and application thereof | |
| CN103142931B (en) | Traditional Chinese medicine composite for treating liver cancer and preparation method thereof | |
| CN103356731B (en) | Pharmaceutical composition containing Cortex Eucommiae extract and Radix Notoginseng total arasaponins and application thereof | |
| CN101829219B (en) | Periplaneta Americana pharmaceutical composition for treating ulcerative colitis and preparation method thereof | |
| CN102205010A (en) | Pharmaceutical composition with auxiliary function of reducing blood fat | |
| CN104306895A (en) | Medicine treating decompensated cirrhosis | |
| CN104258034A (en) | Traditional Chinese medicine composition for boosting immunity | |
| CN103386101A (en) | Traditional Chinese medicine preparation for nonspecific cystitis treatment and preparation method thereof | |
| CN108210595A (en) | Treat Chinese medicine composition of acute-on-chronic liver failure and its preparation method and application | |
| CN107362277A (en) | A kind of composition of strengthen immunity and preparation method thereof | |
| CN105343779A (en) | Traditional Chinese medicine composition capable of lowering blood pressure and protecting blood vessels | |
| CN106581356A (en) | Chinese patent medicine for treating cancer and preparation method thereof | |
| CN105687878A (en) | Traditional Chinese medicine for treating subacute thyroiditis and preparation method thereof | |
| CN105147955A (en) | Orally-taken traditional Chinese medicine pills for treating chronic myeloid leukemia and preparation method | |
| CN104435468A (en) | Traditional Chinese medicine powder for preventing and controlling infectious serositis of ducks | |
| CN104208210B (en) | A kind of Chinese medicine composition treating insulin resistant and relevant disease and preparation method thereof and Chinese medicine preparation | |
| CN101829220A (en) | Periplaneta Americana pharmaceutical composition for treating ulcerative colitis and preparation method thereof | |
| CN102670746B (en) | Anti-platelet activation traditional Chinese medicine composition for treating lupus erythematosus | |
| CN105079310A (en) | Traditional Chinese medicine composition for relieving pain and method for preparing traditional Chinese medicine composition | |
| CN105920519A (en) | Traditional Chinese medicine composition for treating pharyngoconjunctival fever | |
| CN104644746A (en) | Capsule for treating rheumatoid arthritis and preparation method of capsule |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200114 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |