CN106138344A - The new application of rascal - Google Patents

The new application of rascal Download PDF

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Publication number
CN106138344A
CN106138344A CN201510127586.2A CN201510127586A CN106138344A CN 106138344 A CN106138344 A CN 106138344A CN 201510127586 A CN201510127586 A CN 201510127586A CN 106138344 A CN106138344 A CN 106138344A
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Prior art keywords
rascal
stir
vinegar
pericarpium citri
citri reticulatae
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Inventor
钟森
涂翔
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Individual
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    • 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

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  • 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 discloses the new application of a kind of rascal, this new application is rascal or application in the medicine of suppression tumor angiogenesis for the stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar.The medicine of suppression tumor angiogenesis is with the rascal of effective dose or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar as active component, according to pharmacy conventional method, adds the medicament that pharmaceutically acceptable auxiliary material is prepared from.Rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar are applied to suppress tumor angiogenesis by the present invention, can effectively suppress growth of tumour cell, have good medical value, provide a kind of new selection for clinic.

Description

The new application of rascal
Technical field
The invention belongs to field of medicaments, be specifically related to the new application of rascal, especially rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar new in preparation suppression tumour Purposes in the medicine that angiogenic generates.
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 related 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.
Growth, transfer or even prognosis to malignant entity tumor for the Angiogenesis suffers from extremely important meaning.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.
Rascal is rutaceae orange Citrus reticulata Blanco and the fruit of the dry young fruit of variety or immature fruit Skin.Bitter, pungent, warm in nature.There is soothing the liver relieving stagnant Qi, the stagnant effect of long-pendingization that disappear.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.
Although also it has been reported that it has antitumor action, but not finding that it has the effect of suppression tumor angiogenesis.
Content of the invention
First technical problem solved by the invention is to provide the new medicine use of a kind of rascal.
The new medicine use of rascal provided by the present invention is rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar suppresses the medicine of tumor angiogenesis in preparation In new application.
Described medicine is with the rascal of effective dose or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar as active component, according to pharmacy conventional method, adds pharmaceutically The medicament that auxiliary material is prepared from.Concrete can make oral formulations or injection, defeated by oral, intramuscular injection, vein Enter or the mode such as lumbar injection is administered.
Second technical problem solved by the invention is to provide a kind of pharmaceutical composition suppressing tumor angiogenesis, especially, Its main active is rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar, the medicament being prepared from according to pharmacy conventional method.Medicine can also be added during preparation Prepared by the customary adjuvant on.Active component can also increase the effect of Synergistic with addition of other antineoplastics.
Described customary adjuvant include the conventional diluent of pharmaceutical field, excipient, filler, adhesive, wetting agent, disintegrant, Sorbefacient, surfactant, absorption carrier, lubricant etc..
Oral agents, injection can be made with rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar for the medicine suppressing tumor angiogenesis prepared by active component The various ways such as liquid.The medicine of above-mentioned various formulation all can be prepared according to the conventional method of pharmaceutical field.
3rd technical problem solved by the invention is to provide the preparation of the pharmaceutical composition of above-mentioned suppression tumor angiogenesis Method.
One of preferred method: comprise the steps:
A, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar add boiling water, and filter to obtain decoction liquor；
It B, is dried decoction liquor and get final product.
Further, step B is dried decoction liquor and is less than 5% to water content.
One of preferred method: comprise the steps:
A, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar add boiling water, and filter to obtain decoction liquor；
B, decoction liquor, according to pharmacy conventional method, add customary adjuvant to be pharmaceutically prepared.
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 uses rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar suppression tumor angiogenesis effect notable, for clinic suppression tumor neogenetic Angiogenesis and treatment tumour provide a kind of brand-new selection.
Brief description
The juvenile fish light microscopic figure that Fig. 1 rascal is intervened.
The grayscale format figure of the juvenile fish fluorescence microscope display figure that Fig. 2 rascal is intervened.
The grayscale format figure of the juvenile fish high power fluorescence microscope display figure that Fig. 3 rascal is intervened.
The juvenile fish light microscopic figure that Fig. 4 positive control-PTK787 intervenes.
The grayscale format figure of the juvenile fish fluorescence microscope display figure that Fig. 5 positive control-PTK787 intervenes.
The grayscale format figure of the juvenile fish high power fluorescence microscope display figure that Fig. 6 positive control-PTK787 intervenes.
The juvenile fish light microscopic figure that Fig. 7 negative control-Vehicle Control (0.1%DMSO) intervenes.
The grayscale format figure of the juvenile fish fluorescence microscope display figure that Fig. 8 negative control-Vehicle Control (0.1%DMSO) intervenes.
The gray scale lattice of the juvenile fish high power fluorescence microscope display figure that Fig. 9 negative control-Vehicle Control (0.1%DMSO) intervenes Formula figure.
Detailed description of the invention
Experimental technique described in following embodiment, if no special instructions, is conventional method；Described reagent and material, as without spy Different explanation, all commercially obtains.
The test investigating the medicinal new application of rascal is as follows:
Embodiment:
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, 1 hour every time, 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 It in wind drying box, 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 is anaesthetized juvenile fish, is used Nikon SMZ 1500 fluorescence microscopy to take pictures.Internode Vascularization is the leading indicator evaluating drug effect, is also used for evaluating its toxicity simultaneously.
1.4 results and conclusion
Use rascal, the juvenile fish light microscopic figure of positive control-PTK787, negative control-Vehicle Control intervention, fluorescence microscope Fig. 1-9 is shown in respectively by display figure (grayscale format figure), high power fluorescence microscope display figure (grayscale format figure).
The juvenile fish using rascal and PTK787 to intervene all occurs in that the defect of Angiogenesis.Light microscopic and fluorescence microscope show, with 0.1%DMSO negative control compares, the juvenile fish using rascal to intervene, and defines less complete intersegmental blood vessel.High power lens shows Show, be merely able to observe aorta dorsalis seedling once in a while.5 μ g/ml PTK787 positive controls then can completely inhibit intersegmental blood vessel and back Longitudinal blood vessel.Rascal dead or teratogenesis without result in zebra fish, does not find neurotoxicity or the organ toxicity of rascal.
To sum up, the present invention uses rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar suppression tumor angiogenesis effect notable, for clinic suppression tumor neogenetic Angiogenesis and treatment tumour provide a kind of brand-new selection.

Claims (9)

1. rascal or purposes in the medicine of preparation suppression tumor angiogenesis for the stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar.
2. purposes according to claim 1, it is characterised in that: described medicine is with the rascal of effective dose or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar For active component, the medicament being prepared from according to pharmacy conventional method.
3. suppress the pharmaceutical composition of tumor angiogenesis, it is characterised in that: it is with the rascal of effective dose or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar For active component, the medicament being prepared from according to pharmacy conventional method.
4. the pharmaceutical composition for the treatment of tumour according to claim 3, it is characterised in that: described medicament is oral formulations Or injection.
5. the pharmaceutical composition of the treatment tumour according to claim 3 or 4, it is characterised in that: the every preparation of described medicament Unit contains rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar 1～20 gram.
6. the preparation method of the pharmaceutical composition of the suppression tumor angiogenesis described in claim 3, it is characterised in that: bag Include following steps:
Method one: rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar are ground into fine powder, mixing powder；Or
Method two: rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar are ground into fine powder, encapsulated capsule；Or
Method three: rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar are ground into fine powder, compressing tablet i.e. piece agent；Or
Method four: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, filter to obtain decoction liquor；Or
Method five: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, filters to obtain decoction liquor, is dried decoction liquor；Or
Method six: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, concentrated extracting solution makes particle, granule；Or
Method seven: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, concentrated extracting solution makes particle, encapsulated capsule； Or
Method eight: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, concentrated extracting solution makes particle, compressing tablet i.e. piece agent；Or
Method nine: after rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar water boiling and extraction, makes water decoction, or adds customary adjuvant and make oral liquid, sugar Slurry, mixture.
7. the preparation method of the pharmaceutical composition of the suppression tumor angiogenesis described in claim 3, it is characterised in that: bag Include following steps:
A, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar add boiling water, and filter to obtain decoction liquor；
It B, is dried decoction liquor and get final product.
8. the preparation method of the pharmaceutical composition of suppression tumor angiogenesis according to claim 7, it is characterised in that: Described step B is dried decoction liquor and is less than 5% to water content.
9. the preparation method of the pharmaceutical composition of the suppression tumor angiogenesis described in claim 3, it is characterised in that: bag Include following steps:
A, rascal or stir-baked PERICARPIUM CITRI RETICULATAE VIRIDE with vinegar add boiling water, and filter to obtain decoction liquor；
B, decoction liquor, according to pharmacy conventional method, add customary adjuvant to be pharmaceutically prepared.
CN201510127586.2A 2015-02-17 2015-03-23 The new application of rascal Pending CN106138344A (en)

Applications Claiming Priority (2)

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CN201510085413 2015-02-17
CN2015100854139 2015-02-17

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CN201510127617.4A Pending CN106138144A (en) 2015-02-17 2015-03-23 The new application of Radix Rhapontici seu Radix Echinopsis
CN201510127586.2A Pending CN106138344A (en) 2015-02-17 2015-03-23 The new application of rascal
CN201510128977.6A Pending CN106138152A (en) 2015-02-17 2015-03-23 The new application of Flos Chrysanthemi Indici
CN201510127428.7A Pending CN106138102A (en) 2015-02-17 2015-03-23 The new application of turtle shell
CN201610090180.6A Pending CN105878488A (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
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

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CN201510128977.6A Pending CN106138152A (en) 2015-02-17 2015-03-23 The new application of Flos Chrysanthemi Indici
CN201510127428.7A Pending CN106138102A (en) 2015-02-17 2015-03-23 The new application of turtle shell
CN201610090180.6A Pending CN105878488A (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
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

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CN105878490B (en) 2019-12-31
CN106138152A (en) 2016-11-23
CN105878325A (en) 2016-08-24
CN106138102A (en) 2016-11-23
CN105878321A (en) 2016-08-24
CN105878490A (en) 2016-08-24
CN105878488A (en) 2016-08-24
CN105878489A (en) 2016-08-24
CN106138144A (en) 2016-11-23
CN105878326A (en) 2016-08-24
CN105878489B (en) 2020-01-14

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Application publication date: 20161123