CN1839902A - Pharmaceutical composition containing glabrous sarcandra herb extract flavone effective part and its uses - Google Patents

Pharmaceutical composition containing glabrous sarcandra herb extract flavone effective part and its uses Download PDF

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Publication number
CN1839902A
CN1839902A CN 200610049218 CN200610049218A CN1839902A CN 1839902 A CN1839902 A CN 1839902A CN 200610049218 CN200610049218 CN 200610049218 CN 200610049218 A CN200610049218 A CN 200610049218A CN 1839902 A CN1839902 A CN 1839902A
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China
Prior art keywords
flavone
injection
pharmaceutical composition
extract
herba sarcandrae
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CN 200610049218
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Chinese (zh)
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连晓媛
张治针
汤祖麟
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Jiangxi Boshilian Science And Technology Research &development Co Ltd
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Jiangxi Boshilian Science And Technology Research &development Co Ltd
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Priority to CN 200610049218 priority Critical patent/CN1839902A/en
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Abstract

The invention discloses a pharmaceutical composition containing the effective portions of arcandra flavone extract with a purity of 50-99%, the effective portions can be used separately or combined with other plant extracts to obtain preparations of various forms including injections, powder injection, small injection, large injection, and suspension type injection. The preparing process comprises the steps of water grilling, alcohol depositing, extracting with alcohols of different concentration, acetic acid ethyl ester extraction, passing through macroscopic resin columns, and hypercritical extracting.

Description

The medical composition and its use that contains glabrous sarcandra herb extract flavone effective part
Technical field
The present invention relates to the plant amedica Herba Sarcandrae, specifically a kind of pharmaceutical composition flavone that contains Herba Sarcandrae and equal genus plants extract and uses thereof.
Background technology
Herba Sarcandrae (Sarcandra glabra (Thunb) Nakai) is for the dry herb of Chloranthaceae Herba Pileae Scriptae platymiscium has another name called Herba Pileae Scriptae, Herba Pileae Scriptae, Ramulus Sambuci Williamsii, refutes bone tea, atrophic debility of bones wind etc.Be the perennial evergreen draft, be distributed in provinces such as Jiangxi, Anhui, Zhejiang, Hunan, Hubei, Sichuan, Guangdong, Guangxi, Jiangxi Province is the main place of production.Herba Sarcandrae has effects such as blood circulation promoting and blood stasis dispelling, pain relieving, heat-clearing and toxic substances removing.Be used for the treatment of common inflammation, rheumatic arthritis.Be used for assistant treating cancer modern age, multiple malignant tumor such as gastric cancer, cancer of pancreas, hepatocarcinoma, esophageal carcinoma, rectal cancer etc. were had the auxiliary treatment effect.Herba Sarcandrae contains multicomponents such as flavonoid, coumarin, organic acid, volatile oil, saponin, phenols, tannin, polysaccharide.ZHONGJIEFENG ZHUSHEYE, oral liquid, tablet are used for thrombocytopenic purpura patient increased platelets counts, also are used for assistant treating cancer.Present commercially available ZHONGJIEFENG ZHUSHEYE, oral liquid, tablet are Herba Sarcandrae crude extract crude preparation by using, its assay coumarin, organic acid, and it is indeterminate to contain the flavone amount.There is bibliographical information Herba Sarcandrae total flavones class extract to can be used for platelet purpura and assistant treating cancer, the purity of not clear and definite total flavonoid extract, whether more not clear and definite its reaches the purity of (50% to 99%) more than 50%, it is indeterminate to be what degree is the purity of its flavone reaches, and does not more have flavone effective part and injection product thereof approval listing.Stipulate that by national Bureau of Drugs Supervision new drug management method Chinese medicine " effective site " must reach the purity more than 50%, the purity that promptly must reach more than 50% is only Chinese medicine " effective site ".
Summary of the invention
The objective of the invention is to provide pharmaceutical composition of a kind of effective site that contains glabrous sarcandra herb extract flavone and its production and use, the flavone effective part that Herba Sarcandrae extracts reaches the purity of (50% to 99%) more than 50%, makes various injections with this.
Purpose of the present invention can take following method to realize:
A kind of pharmaceutical composition that contains glabrous sarcandra herb extract flavone effective part, the purity that it is characterized in that extracting in the described Herba Sarcandrae effective site of flavone is 50% to 99%.
Described flavone effective part separately or the preparation that mixes or make with other plant extract or compound, its preparation comprises that injection is an injection, comprises injectable powder, small-volume injection, big injection, milkiness type injection, suspension type injection.
Contain the preparation of drug combination method of glabrous sarcandra herb extract flavone effective part, it is characterized in that may further comprise the steps:
The extraction separation of total flavone part and composition:
The flavonoid total extract can select following a kind of method extraction to obtain:
Alcohol reflux extracts, alcohol percolation extracts or decocting boils, wherein:
The alcohol reflux extracting method is:
Get the Chinese medicinal material of sarcandra glaber coarse powder, make solvent, flood after 1 hour with 6~10 times of amounts of 35%~95% ethanol, heating and refluxing extraction 2~4 times, each 1~4 hour, reclaim ethanol, drying promptly gets total extract;
The alcohol percolation extracting method is:
Get the Herba Sarcandrae coarse powder, make solvent with 25%~95% ethanol, behind the dipping, carry out percolation with 1~7ml/ minute speed, collect percolate, reclaim ethanol, drying promptly gets total extract;
Decocting the method for extracting is:
Get Chinese medicinal material of sarcandra glaber and add 6~10 times of water gagings decoctions, each 1~3 hour, filter, filtrate merges, and concentrates, and is drying to obtain total extract;
Separation and purification:
Total flavones and monomer whose effective ingredient can select following a kind of method extraction to obtain:
Macroreticular resin absorbing method, supercritical extraction or organic solvent extraction method, wherein:
The organic solvent extraction method:
Organic solvent ethyl acetate method is extracted the total flavones in the Herba Sarcandrae dry extract: water extracts the dried cream ultrasonic dissolution of Herba Sarcandrae repeatedly with ethyl acetate, gets total flavones;
Supercritical extraction:
The Herba Sarcandrae total extract is inserted in the supercritical extraction device, regulates flow, and pressure 20-50MPa, temperature 100-350 ℃, time 60-120min get the extract total flavones;
Macroreticular resin absorbing method:
Macroporous adsorbent resin extracts the total flavones in the Herba Sarcandrae dry extract: get the total extractum of Herba Sarcandrae, behind the dilute with water, the reuse constant flow pump pumps into pretreated absorption with macroporous adsorbent resin, wash post with water, washing is back with 50~90% ethanol elutions, collect eluent, reclaim ethanol, dry that solid content is total flavones;
Drying means:
Flavone extract behind the separation and purification can adopt oven drying method, boulton process or spray drying method.
The pharmaceutical composition that contains Herba Sarcandrae extract effective site is applied to antitumor action, the efficacy enhancing and toxicity reducing effect, and antitumor is put, the toxic reaction of chemotherapy comprises and alleviates leukopenia and thrombocytopenia.
The pharmaceutical composition that contains Herba Sarcandrae extract effective site is applied to treat bleeding due to blood-heat, ecchymosis, idiopathic thrombocytopenic purpura and secondary thrombocytopenic purpura, increased platelets counts.
The pharmaceutical composition that contains Herba Sarcandrae extract effective site is applied to antimicrobial antiphlogistic, treatment pharyngolaryngitis, tracheobronchitis, pneumonia, keratitis, cellulitis, appendicitis.
The specific embodiment
Describe embodiment of the present invention below in detail.
One, the extraction separation of flavone effective part and assay
Chinese medicine Herba Sarcandrae flavone class total extract of the present invention can alcohol reflux extracts by Herba Sarcandrae is carried out, alcohol percolation extracts or water boiling and extraction obtains, wherein:
A, alcohol reflux extracting method are: get the Chinese medicinal material of sarcandra glaber coarse powder, doubly measure with 35%-95% ethanol 6-10 and make solvent, flood after 1 hour, and heating and refluxing extraction 2-4 time, each 1-4 hour, reclaim ethanol, drying promptly gets total extract;
B, alcohol percolation extracting method are: get the Herba Sarcandrae coarse powder, make solvent with 25%-95% ethanol, behind the dipping, carry out percolation with 1-7ml/ minute speed, collect percolate, reclaim ethanol, drying promptly gets total extract;
The method that C, decoction are extracted is: gets Chinese medicinal material of sarcandra glaber and adds 6-10 times of water gaging decoction, and each 1-3 hour, filter, the filtrate merging concentrates, and is drying to obtain total extract.
Separation and purification: above-mentioned A, B, C Herba Sarcandrae extract, any a kind obtains total flavones through organic solvent extraction method or absorption with macroporous adsorbent resin method or supercritical extraction separation and purification again.
The machine solvent extraction method: organic solvent ethyl acetate method is extracted the total flavones in the Herba Sarcandrae dry extract: with a certain amount of water with the dried cream ultrasonic dissolution of Herba Sarcandrae, extract repeatedly with a certain amount of ethyl acetate, ethyl acetate adopts 3 factors, the extraction of technology road is determined in the test of 3 horizontal quadratures, get content of total flavone greater than 50%, the response rate of total flavones is more than 80%.
Supercritical extraction: Herba Sarcandrae extract, insert in the supercritical extraction device, adjusting flow, pressure 20-50MPa, temperature 100-350C, time 60-120min get extract.Measure the general flavone content in the extract, the response rate of total flavones.The response rate total flavones amount of total flavones is greater than 50%, and the response rate of total flavones is more than 80%.
Macroreticular resin absorbing method: macroporous adsorbent resin extracts the total flavones in the Herba Sarcandrae dry extract: get the total extractum of Herba Sarcandrae, behind the dilute with water, the reuse constant flow pump pumps into pretreated absorption with macroporous adsorbent resin.Wash post with water, washing back 50-90% ethanol elution is collected eluent, reclaims ethanol, and dry that solid content is total flavones, the content of flavone is greater than 50%, and the response rate of total flavones is more than 80%.
Determination of total flavonoids: the reference substance solution preparation: precision takes by weighing the control substance of Rutin 100mg of 105 ℃ of drying under reduced pressure to constant weight, put in the 100ml volumetric flask, add 60% ethanol 70ml, put slight fever dissolving in the water-bath, put cold, add 60% ethanol dilution to scale, shake up, the accurate 10ml that draws, put in the 50ml volumetric flask, add water to scale, shake up, promptly.
Standard curve preparation: the accurate reference substance solution 1.0,2.0,3.0 of drawing, 4.0,5.0, put respectively in the 25ml measuring bottle with 6.0ml, respectively add water 5ml, add 5% sodium nitrite solution 1ml, shake up, placed 6 minutes, add 10% sodium nitrate solution 1ml, shake up, placed 6 minutes, hydro-oxidation sodium test solution 10ml, add water to scale again, shake up, placed 15 minutes, do blank with method with 6ml water, measure trap according to spectrophotography at the wavelength place of 500nm, with the trap is vertical coordinate, and concentration is abscissa, the drawing standard curve.
The need testing solution preparation: precision takes by weighing total extract 20mg, puts in the 25ml volumetric flask, adds 70% ethanol 10ml, dissolving, and thin up is settled to scale, shakes up, promptly.The accurate 1ml that draws, put in the 25ml measuring bottle, method under the sighting target directrix curve preparation is operated from " respectively adding water 5ml ", with need testing solution 1ml in accordance with the law, thin up is done blank to 25ml, filter, get filtrate and measure trap in accordance with the law, read the weight of rutin the need testing solution from standard curve, calculate, promptly.
Total flavonoid calculates with rutin and contains the purity that reaches more than 50% to 99% after measured.
Drying means: the flavone extract behind the separation and purification of the present invention can adopt oven drying method, boulton process, spray drying method.Oven drying method, boulton process are long drying time, must be predrying in water-bath before the vacuum drying, with moisture Control in 20%, easy-to-drawly during vacuum drying driedly become cellular, drying can be finished in 2~3 days, otherwise, the water content height can overflow during vacuum drying, and the oven drying method required time is longer.The spray drying time is short, can finish in a few hours.How three kinds of methods are selected, visual physical condition.
Two, white platelet-increasing role is used and risen to the antitumor of total flavone valid target and antineoplastic efficacy enhancing and toxicity reducing
Flavone effective part and be mixed with injection integral experiment and experiment in vitro has all proved significantly directly antineoplastic action and efficacy enhancing and toxicity reducing effect, antitumor, put, the toxic reaction of chemotherapy comprises and alleviates leukopenia and thrombocytopenia, also can be applicable to constitutional platelet purpura and Secondary cases platelet purpura, increased platelets counts and antimicrobial antiphlogistic.
(1) integral experiment: by to the kinds of tumors evidence, the flavone effective part that we propose and be mixed with injection directly antineoplastic action is arranged significantly.
1, direct anti-tumor experiment: at direct anti-mice S 180Solid tumor test and direct anti-mice S 180The test of ascitic type tumor, by lumbar injection, intramuscular injection, tail vein injection mode administration cyclophosphamide, at present commercially available ZHONGJIEFENG ZHUSHEYE, the effective site of Herba Sarcandrae flavone (50% to 99%) purity more than 50%, experimental result shows that Herba Sarcandrae flavone effective site tumour inhibiting rate between 30% and 50%, makes S 180The increase in life span 60~156% of mice with tumor, flavone effective part have significantly directly antineoplastic action.
Table 1 Herba Sarcandrae flavone effective site antitumor S 180The result (x ± s, n=10)
Group Route of administration Dosage (mg/kg) Tumor heavy (g) Suppression ratio (%)
Normal saline iv 0.1ml/10g 1.7898
Cyclophosphamide ip 80mg/kg 0.08301 95%
ZHONGJIEFENG PIAN op 18g crude drug/kg 1.6001 11%
ZHONGJIEFENG ZHUSHEYE iv 8g crude drug/kg 1.4101 21%
Herba Sarcandrae flavone iv 100mg/kg 1.2216 32%
2, synergism experiment: cyclophosphamide treatment mice S 180In the solid tumor synergism test, be that 20mg/kg adds the effective site with Herba Sarcandrae flavone (50% to 99%) purity more than 50% respectively by lumbar injection, intramuscular injection, tail vein injection mode administration cyclophosphamide minimizing dosage 20mg/kg and cyclophosphamide dosage.Experimental result shows that single tumour inhibiting rate of cyclophosphamide 20mg/kg of using is between 5% and 20%, and tumour inhibiting rate illustrated when Herba Sarcandrae flavone effective site and cyclophosphamide share obviously to strengthen chemotherapeutic cyclophosphamide antitumor action between 30% and 70% when Herba Sarcandrae flavone effective site was share.
Table 2 Herba Sarcandrae flavone effective site antitumor S 180The synergism experiment result (x ± s, n=10)
Group Route of administration Dosage (mg/kg) Tumor heavy (g) Suppression ratio (%)
Normal saline iv 0.1ml/10g 1.9810
Cyclophosphamide ip 20mg/kg 1.6381 17%
Cyclophosphamide 20mg/kg+ ZHONGJIEFENG ZHUSHEYE iv 18g crude drug/kg 1.4301 28%
Cyclophosphamide 20mg/kg+ flavone ip+iv 100mg/kg 1.1022 44%
3, attenuation experiment: the flavone in (50% to 99%) purity more than 50% is treated mice S to cyclophosphamide, cytosine arabinoside 180In the solid tumor attenuation test, by lumbar injection, intramuscular injection, tail vein injection these four kinds of mode administration cyclophosphamide, cytosine arabinosides with add the injection of Herba Sarcandrae flavone effective site of (50% to 99%) purity more than 50% respectively.Experimental result shows that mice all platelet occurs behind administration cyclophosphamide, cytosine arabinoside and leukocyte significantly descends, after adding Herba Sarcandrae flavone effective site respectively, leukocyte and platelet significantly rise, and illustrate that Herba Sarcandrae flavone effective site and chemotherapeutic have tangible Attenuation when share.
Table 3 Herba Sarcandrae flavone effective site antitumor S 180The attenuation experimental result (x ± s, n=10)
Group Route of administration Dosage (mg/kg) PLT (10 9/L) WBC (10 9/L)
Normal saline iv 0.1ml/10g 543.80±52.24 9.92+3.13
Cyclophosphamide ip 20mg/kg 342.12±89.86 3.48+1.07
Cyclophosphamide 20mg/kg+ ZHONGJIEFENG ZHUSHEYE iv 18g crude drug/kg 393.44±23.45 4.53+1.62
Cyclophosphamide 20mg/kg+ Herba Sarcandrae flavone injection ip+iv 100mg/kg 475.01±73.96 7.52+1.62
(2) experiment in vitro
1, the effect of cultured tumor cells in vitro growth inhibited is tested: at mice S to In vitro culture 180, ovarian cancer SKOV cell, cancer of pancreas SW1990 cell the Growth Inhibition experiment in, Herba Sarcandrae flavone effective site between 20% to 95%, illustrates that the effective site of flavone (50% to 99%) purity more than 50% has antitumor action to the suppression ratio of above-mentioned growth of tumour cell.
2, external bacteriostatic experiment: in extracorporeal bacteria inhibitor test, adopt 15 kind of 117 strain bacterium such as bacillus pyocyaneus, pneumobacillus, Bacillus proteus, escherichia coli, Candida albicans, staphylococcus aureus, dysentery bacterium, Bacillus typhi, paratyphoid bacillus A, first streptococcus, micrococcus catarrhalis, hemophilus influenza, Diplococcus pneumoniae, streptococcus and bacteroides fragilis, show that through MIC and MSC test the effective site of (50% to 99%) purity more than 50% has antibacterial action in various degree.

Claims (5)

1, a kind of pharmaceutical composition that contains glabrous sarcandra herb extract flavone effective part is characterized in that the purity of the flavone effective part that extracts in the described Herba Sarcandrae is 50% to 99%.
2, the pharmaceutical composition that contains glabrous sarcandra herb extract flavone effective part according to claim 1, it is characterized in that separately or the preparation that mixes or make with other plant extract or compound with described flavone effective part, its preparation comprises that injection is an injection, comprises injectable powder, small-volume injection, big injection, milkiness type injection, suspension type injection.
3, the application that contains the pharmaceutical composition of Herba Sarcandrae flavone extract effective site according to claim 1 and 2, it is characterized in that being applied to antitumor action, efficacy enhancing and toxicity reducing effect, antitumor are put, the toxic reaction of chemotherapy comprises and alleviates leukopenia and thrombocytopenia.
4, the application that contains the pharmaceutical composition of Herba Sarcandrae flavone extract effective site according to claim 1 and 2, it is characterized in that being applied to treat bleeding due to blood-heat, ecchymosis, idiopathic thrombocytopenic purpura and secondary thrombocytopenic purpura, increased platelets counts.
5, the application that contains the pharmaceutical composition of Herba Sarcandrae flavone extract effective site according to claim 1 and 2 is characterized in that being applied to antimicrobial antiphlogistic, treatment pharyngolaryngitis, tracheobronchitis, pneumonia, keratitis, cellulitis, appendicitis.
CN 200610049218 2006-01-18 2006-01-18 Pharmaceutical composition containing glabrous sarcandra herb extract flavone effective part and its uses Pending CN1839902A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101665479B (en) * 2009-09-22 2012-05-16 三明华健生物工程有限公司 Technology for synchronously extracting isofraxidin and flavonoids compounds from sarcandra glabra and applications thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101665479B (en) * 2009-09-22 2012-05-16 三明华健生物工程有限公司 Technology for synchronously extracting isofraxidin and flavonoids compounds from sarcandra glabra and applications thereof

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