CN101019897A - Antitumor medicine composition and its prepn - Google Patents
Antitumor medicine composition and its prepn Download PDFInfo
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- CN101019897A CN101019897A CNA2006101657073A CN200610165707A CN101019897A CN 101019897 A CN101019897 A CN 101019897A CN A2006101657073 A CNA2006101657073 A CN A2006101657073A CN 200610165707 A CN200610165707 A CN 200610165707A CN 101019897 A CN101019897 A CN 101019897A
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Abstract
The present invention discloses one kind of antitumor medicine composition and its preparation process. The antitumor medicine composition consists of aweto and saponin. The present invention provides also the antitumor use of the medicine composition.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of antitumor medicine composition and preparation method thereof.
Background technology
Cancer is the disease of serious harm human health, and the statistics that World Health Organization (WHO) announces shows: about 1,000 ten thousand people of annual whole world pathogenesis of cancer, dead about 7,000,000 people.Much bigger the toxic and side effects of the cancer therapy drug of clinical practice at present is.Therefore research and develop safely and efficiently that anticarcinogen is the task of top priority, particularly the new anticarcinogen of exploitation is the heat subject of new drug research always from traditional Chinese medicine of extensive knowledge and profound scholarship.
Radix Notoginseng is a rare Chinese medicine, and traditional traditional Chinese medical science is thought " ginseng qi-tonifying the first, Radix Notoginseng enrich blood first ", in China's rare medicinal herbs be treatment extensively, health-care effect persistent " strengthening the body resistance " food medicine dual purpose product.Radix Notoginseng is quite widely to the influence of body immune system, and it can promote the propagation and the activation of body granulocyte mononuclear phagocyte system.Can make the T lymphopoiesis, higher dosage has the effect that promotes bone-marrow-derived lymphocyte, plays adjusting under pathology immunological disease situation, and certain effect is also arranged in antitumor.Radix Notoginseng total arasaponins has significant sedation, and can work in coordination with the inhibitory action of central depressant.Cordyceps also is traditional rare medicinal herbs, sees clearly essentials of Matea Medica at first and goes into the lung meridian cough-relieving, again as Liver and kidney giving young employees remedial-courses in general knowledge and vocational skills good merchantable brand.The analysis showed that through modern science Cordyceps contains tens of kinds of trace element such as fungus polysaccharide, cordycepin and several amino acids, vitamin, enzyme, calcium, phosphorus, zinc, has the raising body immune function, promote hemopoietic and metabolic function.Cordyceps decoct lumbar injection can obviously suppress the mice voluntary activity, prolongs mice pentobarbital sodium length of one's sleep.So saponin, Cordyceps binding energy are improving immune function of human body, are improving the better health-care effect of performance in the sleep.Before the present invention, there is not report about pharmaceutical composition antitumor action of the present invention.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition and preparation method thereof, and another purpose of the present invention is to provide the purposes of this drug combination preparation.The present invention seeks to be achieved through the following technical solutions:
The present invention forms by following two flavor raw materials:
Natural cs 1-4 weight portion ginsenoside 1-4 weight portion.
The best proportioning of above-mentioned three flavor crude drug is as follows:
Natural cs 2 weight portion ginsenosides 3 weight portions.
The proportioning of above-mentioned three flavor crude drug is as follows:
Natural cs 3 weight portion ginsenosides 2 weight portions.
The proportioning of above-mentioned three flavor crude drug is as follows:
Natural cs 3 weight portion ginsenosides 4 weight portions.
Above-mentioned composition can be made tablet, soft capsule, capsule, slow releasing agent, granule, drop pill, oral liquid or lyophilized injectable powder.
Crude drug ginsenoside's of the present invention concrete preparation technology is as follows:
Get 5-15 order Radix Ginseng or Radix Notoginseng coarse powder, with 40-100% alcohol reflux 1-4 time, each 1-3 hour, collect extracting solution, filter, filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 1.5-2 hour, concentrated solution adds the equal-volume distilled water, stir, filter, filtrate is crossed macroporous adsorptive resins absorption; Doubly measure resin bed volume distilled water flush away water-solubility impurity with 2-4, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 20-50% ethanol elution, 20-50% ethanol consumption is that 1-5 doubly measures the resin bed volume, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is the chloroform of 30-100: 10-50: 2-20: methanol: subsurface layer; Developer: 5-20% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use the 20-50% ethanol elution, use the 30-100% ethanol elution instead, and collect eluent; Eluent decoloured with 0.5-2% active carbon reflux in 0.5-2 hour, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 30-100% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 30-70% acetic acid, the 20-50% citric acid, 20-50% oxalic acid, the 20-50% malonic acid, 0.5-2% hydrochloric acid, in vitriolic water of 0.5-2% or the alcoholic solution, the control reaction condition: hydrolysis temperature is 20 ℃-100 ℃, hydrolysis time is 0.5 hour-10 hours, after finishing, acid hydrolytic reaction adds and acid hydrolysis liquid equal-volume distilled water, be neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate, with 10 times of weight distilled water, divide and wash precipitation 2-3 time, vacuum drying is pulverized, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in the 5-10 times of weight 50-140% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 0.5-2 hour of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 30-100% ethanol elution resin absorption, recovery ethanol is to the 1/4-3/4 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about the 4-5% of protopanoxadiol saponins inventory.
Concrete preparation technology's preferred for preparation method of crude drug saponin of the present invention is as follows:
Get 10 order Radix Ginsengs or Radix Notoginseng coarse powder,, each 2 hours, collect extracting solution with 70% alcohol reflux 3 times, filter, filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 2 hours, concentrated solution adds the equal-volume distilled water, stirs, and filters, and filtrate is crossed macroporous adsorptive resins absorption; With 3 times of amount resin bed volume distilled water flush away water-solubility impurities, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 35% ethanol elution, 35% ethanol consumption is 2.5 times of amount resin bed volumes, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is 65: 35: 10 a chloroform: methanol: subsurface layer; Developer: 10% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use 35% ethanol elution, use 65% ethanol elution instead, and collect eluent; Eluent decoloured with 1% active carbon reflux in 0.5 hour, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 65% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 50% acetic acid or 1% hydrochloric acid hydrolysis time: hydrochloric acid hydrolysis 1 hour, acetolysis 6 hours, hydrolysis temperature is 75 ℃, adds and acid hydrolysis liquid equal-volume distilled water after acid hydrolytic reaction is finished, and is neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate,, divide and wash precipitation 2-3 time with 10 times of weight distilled water, vacuum drying, pulverize, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in 8 times of weight 95% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 0.5 hour of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 95% ethanol elution resin absorption, recovery ethanol is to 1/2 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about 5% of protopanoxadiol saponins inventory.
Saponin of the present invention contains the ginsenoside Rh
220%-25% and ginsenoside Rg
340%-50%.
Following experiment and embodiment are used to further specify but are not limited to the present invention.
Experimental example: the Radix Notoginseng-cultured Cordyceps mixed powder suppresses the murine melanoma effect experiment
Select murine melanoma (B for use
16) animal model, observe the Radix Notoginseng-cultured Cordyceps mixed powder to B
16The general situation of mice, tumor control rate influence.
1 material
1.1 animal and tumor piece
The purebred mice of male C57, body weight 20 ± 2g buy (quality certification number: the capital is moving is betrothed to 004049) by Beijing Vital River Experimental Animals Technology Co., Ltd., and the cleaning level environment of first key lab of clinical medicine institute of Beijing University of Chinese Medicine is raised down; Mouse melanin (B
16) the tumor piece provides by the Tumour Inst., Chinese Medical Academy experimental center.
1.2 medicine and reagent
The Rh of extraction separation in the Radix Notoginseng
2, Rg
3And natural cs extraction composition is provided by Tianxiu Plant Sci-Tech Development Co., Ltd., Yunnan.Need according to experiment, researcher mixes above three kinds of compositions according to different proportion compatibilities.The compatibility mixed proportion is as follows: saponin Rh
2, Rg
3Mixed powder was according to 1: 1 ratio; The Radix Notoginseng-cultured Cordyceps mixed powder is for 1 group: Cordyceps: saponin is 2: 3 ratios; The Radix Notoginseng-cultured Cordyceps mixed powder is for 2 groups: Cordyceps: saponin is 3: 2 ratios; The Radix Notoginseng-cultured Cordyceps mixed powder is for 3 groups: Cordyceps: saponin is 3: 4 ratios.Three strong board cyclophosphamide are produced (lot number 050405) by Hualian Pharmaceutical Co., Ltd., Shanghai, buy Chinese traditional Chinese medicines group head office.
2 methods
2.1 set up model
Set up murine melanoma (B according to pertinent literature
16) animal model
[5]Select the vigorous B of tumor growth
16Tumor-bearing mice, aseptic condition take out the tumor piece down, add PBS and make single cell suspension with glass homogenizer by dilution in 1: 4, adjust cell number and are about 5 * 10
6/ L, respectively getting 0.2ml, to be inoculated in C57 mice right fore axillary fossa subcutaneous, and inoculation time was finished in 1 hour.
2.2 grouping administration
To inoculate B
16The C57 mice of cell is divided into 10 groups at random, 8/group.That is: 1. normal control group; 2. model control group; 3. cyclophosphamide group; 4. Rh
2Group; 5. Rg
3Group; 6. natural cs group; 7. Rh
2With Rg3 mixed powder group; 8. the Radix Notoginseng-cultured Cordyceps mixed powder is 1 group; 9. the Radix Notoginseng-cultured Cordyceps mixed powder is 2 groups; 10. the Radix Notoginseng-cultured Cordyceps mixed powder is 3 groups.This experiment removes the cyclophosphamide group with (next day 1 time, totally 3 times) medication of 50mg/ (kgd) lumbar injection, and all the other each groups are employing filling stomach administration, feedwater all.For favourable laboratory observation and evaluation effect, except that cyclophosphamide, drug dose is 10mg/ (kgd).Experimental drug with anhydrous alcohol solution after, be mixed with desired concn with normal saline dilution again, in inoculation back gastric infusion next day, every day 1 time, totally 10 days, put to death mice on the 15th day, the preparation specimen is equipped with inspection.
2.3 observation index
Dynamic observe the general upgrowth situation of mice, body weight and animal dead situation in the experimentation.The neck of weighing and took off in the 15th day puts to death mice, peel off tumor weighs, and calculates tumour inhibiting rate according to formula.Tumour inhibiting rate (%)=(the average tumor of the average tumor weight/model control group of 1-administration group is heavy) * 100%; Organ index (mgg
-1)=internal organs quality/body constitution amount * 1000.
2.4 statistical method
All The data SPSS14.0 statistical softwares handle, and enumeration data adopts
Expression;
Many groups data mean relatively adopts one factor analysis of variance, and when P＜0.05, expression has statistical significance.
3 results
3.1 general situation is observed
Respectively organize mice before the experiment generally in order, experiment finishes the back mice all survives.Dynamic observe in the experimentation and respectively organize the general situation of mice and find, model group, the general situation of CTX group mice are relatively poor, mainly show as carrying out property bradykinesia, be slow in action, food-intake minimizing, emaciated physique, the few gloss of hair color, and depilation phenomenon is arranged.Especially more obvious with the CTX group.Surplus each experimental mice hair color gloss, appetite increase, reaction and kinestate are good.Wherein, with mice state the bests of 3: 1 proportion compatibilities of Radix Notoginseng-cultured Cordyceps mixed powder.Ratio was taken second place in 3: 4.From dynamic observing as can be seen, arasaponin, Cordyceps and saponin and Cordyceps mixed powder can obviously improve model mice allomeric function state, improve the quality of living, and have tangible centralizing function.
3.2 body weight change
The preceding another name that divides of administration is respectively organized the mice body weight, compares not statistically significant between each group.Test and finish the back demonstration, model group, CTX group mice body weight obviously descend, and all the other respectively organize the mice body weight all increase in various degree, organizes relatively with model group, CTX, has statistical significance, and experimental result sees Table 1.
Table 1 respectively organize the mice average weight relatively (
)
| Group | Number of elements | Δ body weight (g) | P 1 | P 2 | P 3 | P 4 |
| The normal control group | 8 | 2.56±1.32 | - | - | - | - |
| Model control group | 8 | 1.17±1.63 | ＜0.05 | - | - | - |
| The CTX matched group | 8 | -1.27±1.45 | ＜0.01 | ＜0.01 | - | - |
| Rh 2The dosage group | 8 | 3.34±0.98 | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| Rg 3The dosage group | 8 | 3.45±1.14 | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| The natural cs group | 8 | 3.89±1.07 | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| Saponin mixture group | 8 | 3.68±1.28 | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| Radix Notoginseng-cultured Cordyceps group 1 | 8 | 3.64±1.45* | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| Radix Notoginseng-cultured Cordyceps group 2 | 8 | 3.99±1.49* | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
| Radix Notoginseng-cultured Cordyceps group 3 | 8 | 3.61±1.28* | ＜0.01 | ＜0.05 | ＜0.01 | ＞0.05 |
Annotate 1: adopt the Anova check, P
1For mice body weight and normal mouse weight ratio P value are respectively organized in experiment; P
2For mice body weight and model group mice weight ratio P value are respectively organized in experiment; P
3For mice body weight and CTX group mice weight ratio P value are respectively organized in experiment; P
4For Radix Notoginseng-cultured Cordyceps experiment respectively organize the mice body weight respectively with Rh
2Dosage group, Rg
3Dosage group, natural cs group, saponin mixture group mice weight ratio P value.
Annotate 2: Δ average weight variable quantity=(body weight before treatment back body weight-treatment)
By table 1 analysis following result is arranged: 1. compare with the normal control group, CTX group, model group mice body weight obviously descend.Illustrate that tumor can cause physical consumption, weight loss, and CTX has obviously promoted this pathology process.2. administration is respectively organized all to have obviously and is alleviated/stop mice weight loss effect, wherein, and with natural cs and Radix Notoginseng-cultured Cordyceps mixed powder the best.Observe as can be seen Radix Notoginseng main active Rh in conjunction with mice general state in the experimentation
2With Rg
3, Cordyceps can regulate the mice functional status, the quality of making the life better, the most obvious with the Cordyceps effect especially.Cordyceps has nourishing effects, and regulating allomeric function may be one of key mechanism of its antineoplaston.
3.3 tumor control rate
After experiment finishes, take out respectively and respectively organize mouse tumor and weigh, calculate tumor control rate according to formula.The results are shown in Table 2.
Table 2 respectively organize tumor control rate relatively (
)
| Group | Number of elements | Tumor heavy (g) | Tumour inhibiting rate (%) | P 1 | P 2 | P 3 | P 4 | P 5 |
| Model control group | 8 | 3.32±1.24 | - | - | - | - | - | - |
| The CTX matched group | 8 | 0.31±0.37 | 90.6 | ＜0.01 | - | - | - | - |
| Rh 2The dosage group | 8 | 2.32±0.76 | 30.1 | ＜0.05 | - | - | - | - |
| Rg 3The dosage group | 8 | 2.62±1.11 | 21.1 | ＞0.05 | - | - | - | - |
| The natural cs group | 8 | 2.06±1.15 | 38.1 | ＜0.05 | - | - | - | - |
| Saponin mixture group | 8 | 2.03±1.05 | 39.2 | ＜0.05 | - | - | - | - |
| Radix Notoginseng-cultured Cordyceps group 1 | 8 | 2.07±0.87 | 42.0 | ＜0.05 | ＜0.05 | ＜0.01 | ＜0.05 | ＜0.05 |
| Radix Notoginseng-cultured Cordyceps group 2 | 8 | 1.70±0.66 | 48.0 | ＜0.01 | ＜0.01 | ＜0.01 | ＜0.05 | ＜0.05 |
| Radix Notoginseng-cultured Cordyceps group 3 | 8 | 2.11±0.90 | 36.4 | ＜0.05 | ＜0.05 | ＜0.01 | ＞0.05 | ＞0.05 |
Annotate: adopt the Anova check, P1 respectively organizes tumor control rate and model group P value relatively for experiment; P2 is Rh2 group tumor control rate and each group of Radix Notoginseng-cultured Cordyceps mixed powder P value relatively; P3 is each group of Rg3 group and Radix Notoginseng-cultured Cordyceps mixed powder P value relatively; P4 is natural cs group and each group of Radix Notoginseng-cultured Cordyceps mixed powder P value relatively; P5 is saponin mixed powder and each group of Radix Notoginseng-cultured Cordyceps mixed powder P value relatively
Analyze as can be seen from table 2: 1. remove Rg
3Outside the group, experimental drug is respectively organized tumor control rate all more than 30%, and the single composition is with natural cs tumour inhibiting rate the best, Rh
2Take second place.2. Rh
2, Rg
3Tumour inhibiting rate after the combination is higher than the single composition, has certain collaborative addition.3. the Radix Notoginseng-cultured Cordyceps mixed powder tumour inhibiting rate by different proportion compatibilities is higher than the single composition, has the obvious synergistic additive effect, wherein, with Cordyceps, saponin ratio is 3: 2 curative effect the bests, ratio was taken second place in 2: 3, and ratio was minimum in 3: 4, and is similar to natural cs, saponin mixture tumour inhibiting rate.More than the different proportion compatibility of explanation Cordyceps has some influences to tumor control rate.
4, conclusion
B is selected in this experiment for use
16Animal model is observed Radix Notoginseng and natural cs mixed powder to the general situation of model mice, body weight and tumor control rate influence.Result of study shows: 1. compare with the normal control group, CTX group, model group mice body weight obviously descend, especially with CTX group fall maximum.Illustrate that tumor can cause physical consumption, weight loss, and CTX has obviously promoted this pathology process.2. administration is respectively organized all to have obviously and is alleviated/stop mice weight loss effect, wherein, and with natural cs and Radix Notoginseng-cultured Cordyceps mixed powder the best.Observe as can be seen in conjunction with mice general state in the experimentation, Radix Notoginseng main active, Cordyceps can be regulated the mice functional status, and the quality of making the life better is the most obvious with the Cordyceps effect especially.Cordyceps has nourishing effects, and regulating allomeric function may be one of key mechanism of its antineoplaston.3. remove Rg
3Outside the group, experimental drug is respectively organized tumor control rate all more than 30%, and the single composition is with natural cs tumour inhibiting rate the best, Rh
2Take second place.4. Rh
2, Rg
3Tumour inhibiting rate after the combination is higher than the single composition, has certain collaborative addition.5. the Radix Notoginseng-cultured Cordyceps mixed powder tumour inhibiting rate by different proportion compatibilities is higher than the single composition, has the obvious synergistic additive effect, wherein, with Cordyceps, saponin ratio is 3: 2 curative effect the bests, ratio was taken second place in 2: 3, and ratio was minimum in 3: 4, and is similar to natural cs, saponin mixture tumour inhibiting rate.More than the different proportion compatibility of explanation Cordyceps has some influences to tumor control rate.
Following embodiment all can realize the effect of above-mentioned experimental example
The specific embodiment
Embodiment 1: the preparation of oral gel
Natural cs 2kg ginsenoside 3kg adds conventional adjuvant and makes oral gel.
Above-mentioned ginsenoside's preparation method is as follows:
Get 10 order Radix Ginsengs or Radix Notoginseng coarse powder,, each 2 hours, collect extracting solution with 70% alcohol reflux 3 times, filter, filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 2 hours, concentrated solution adds the equal-volume distilled water, stirs, and filters, and filtrate is crossed macroporous adsorptive resins absorption; With 3 times of amount resin bed volume distilled water flush away water-solubility impurities, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 35% ethanol elution, 35% ethanol consumption is 2.5 times of amount resin bed volumes, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is 65: 35: 10 a chloroform: methanol: subsurface layer; Developer: 10% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use 35% ethanol elution, use 65% ethanol elution instead, and collect eluent; Eluent decoloured with 1% active carbon reflux in 0.5 hour, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 65% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 50% acetic acid or 1% hydrochloric acid hydrolysis time: hydrochloric acid hydrolysis 1 hour, acetolysis 6 hours, hydrolysis temperature is 75 ℃, adds and acid hydrolysis liquid equal-volume distilled water after acid hydrolytic reaction is finished, and is neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate,, divide and wash precipitation 2-3 time with 10 times of weight distilled water, vacuum drying, pulverize, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in 8 times of weight 95% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 0.5 hour of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 95% ethanol elution resin absorption, recovery ethanol is to 1/2 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about 5% of protopanoxadiol saponins inventory.
Embodiment 2: the preparation of capsule
Natural cs 3kg ginsenoside 2kg adds conventional adjuvant and makes capsule.
Above-mentioned ginsenoside's preparation method is as follows:
Get 15 order Radix Ginsengs or Radix Notoginseng coarse powder,, each 2 hours, collect extracting solution with 60% alcohol reflux 4 times, filter, filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 2 hours, concentrated solution adds the equal-volume distilled water, stirs, and filters, and filtrate is crossed macroporous adsorptive resins absorption; With 4 times of amount resin bed volume distilled water flush away water-solubility impurities, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 30% ethanol elution, 60% ethanol consumption is 4 times of amount resin bed volumes, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is 65: 45: 10 a chloroform: methanol: subsurface layer; Developer: 10% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use 30% ethanol elution, use 60% ethanol elution instead, and collect eluent; Eluent decoloured with 2% active carbon reflux in 2 hours, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 80% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 50% acetum, the control reaction condition: hydrolysis temperature is 65 ℃, and hydrolysis time is 8 hours, after finishing, acid hydrolytic reaction adds and acid hydrolysis liquid equal-volume distilled water, be neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate, with 10 times of weight distilled water, divide and wash precipitation 2 times, vacuum drying is pulverized, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in 10 times of weight 85% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 2 hours of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 85% ethanol elution resin absorption, recovery ethanol is to 2/3 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about 4% of protopanoxadiol saponins inventory.
Embodiment 3: the preparation of drop pill
Natural cs 3kg ginsenoside 4kg adds conventional adjuvant and makes drop pill.
Claims (9)
1, a kind of antitumor medicine composition is characterized in that this pharmaceutical composition made by following raw material medicaments: natural cs 1-4 weight portion saponin 1-4 weight portion.
2, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments: natural cs 2 weight portion saponin 3 weight portions.
3, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments: natural cs 3 weight portion saponin 2 weight portions.
4, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments: natural cs 3 weight portion saponin 4 weight portions.
5,, it is characterized in that said composition makes tablet, soft capsule, capsule, slow releasing agent, granule, drop pill, oral liquid or lyophilized injectable powder as claim 1,2,3 or 4 described pharmaceutical compositions.
6, claim 1,2,3 or 4 described preparation of drug combination methods is characterized in that this method is: get 5-15 order Radix Ginseng or Radix Notoginseng coarse powder, use 40-100% alcohol reflux 1-4 time, each 1-3 hour, collect extracting solution, filter filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 1.5-2 hour, concentrated solution added the equal-volume distilled water, stirs, filter, filtrate is crossed macroporous adsorptive resins absorption; Doubly measure resin bed volume distilled water flush away water-solubility impurity with 2-4, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 20-50% ethanol elution, 20-50% ethanol consumption is that 1-5 doubly measures the resin bed volume, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is the chloroform of 30-100: 10-50: 2-20: methanol: subsurface layer; Developer: 5-20% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use the 20-50% ethanol elution, use the 30-100% ethanol elution instead, and collect eluent; Eluent decoloured with 0.5-2% active carbon reflux in 0.5-2 hour, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 30-100% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 30-70% acetic acid, the 20-50% citric acid, 20-50% oxalic acid, the 20-50% malonic acid, 0.5-2% hydrochloric acid, in vitriolic water of 0.5-2% or the alcoholic solution, the control reaction condition: hydrolysis temperature is 20 ℃-100 ℃, hydrolysis time is 0.5 hour-10 hours, after finishing, acid hydrolytic reaction adds and acid hydrolysis liquid equal-volume distilled water, be neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate, with 10 times of weight distilled water, divide and wash precipitation 2-3 time, vacuum drying is pulverized, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in the 5-10 times of weight 50-140% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 0.5-2 hour of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 30-100% ethanol elution resin absorption, recovery ethanol is to the 1/4-3/4 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about the 4-5% of protopanoxadiol saponins inventory.
7, the preparation method of Chinese medicine composition as claimed in claim 5 is characterized in that this method is: get 10 order Radix Ginsengs or Radix Notoginseng coarse powder, with 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter filtrate recycling ethanol, after not having the ethanol flavor, vacuum concentration 2 hours, concentrated solution adds the equal-volume distilled water, stirs, filter, filtrate is crossed macroporous adsorptive resins absorption; With 3 times of amount resin bed volume distilled water flush away water-solubility impurities, absorption ginsenoside's resin column is standby; With above-mentioned adsorption resin column 35% ethanol elution, 35% ethanol consumption is 2.5 times of amount resin bed volumes, follows the tracks of with thin layer chromatography and detects, and thin layer chromatography wherein is: developing solvent is 65: 35: 10 a chloroform: methanol: subsurface layer; Developer: 10% ethanol solution of sulfuric acid; After occurring protopanoxadiol saponins speckle on the thin layer chromatography, stop to use 35% ethanol elution, use 65% ethanol elution instead, and collect eluent; Eluent decoloured with 1% active carbon reflux in 0.5 hour, filter and remove active carbon, filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the protopanoxadiol saponins of 65% ethanol elution resin absorption, recovery ethanol, vacuum concentration, vacuum drying is pulverized, and gets the protopanoxadiol saponins; Get above-mentioned protopanoxadiol saponins powder and be dissolved in 50% acetic acid or 1% hydrochloric acid hydrolysis time: hydrochloric acid hydrolysis 1 hour, acetolysis 6 hours, hydrolysis temperature is 75 ℃, adds and acid hydrolysis liquid equal-volume distilled water after acid hydrolytic reaction is finished, and is neutralized to neutrality with 6% sodium hydroxide solution, filter, collect the precipitation of the secondary saponin of hydrolyzate,, divide and wash precipitation 2-3 time with 10 times of weight distilled water, vacuum drying, pulverize, get the thick secondary saponin powder of hydrolyzate, standby; The thick secondary saponin powder of hydrolyzate is dissolved in 8 times of weight 95% ethanol, and dissolving is filtered, filtrate is filtered and is removed active carbon with the decolouring in 0.5 hour of 1% active carbon reflux, and filtrate is crossed macropore positive and negative ion exchange column, further decolouring desalination remove impurity, and with the secondary saponin of 95% ethanol elution resin absorption, recovery ethanol is to 1/2 of eluent cumulative volume, cooling, place crystallization, vacuum filtration is collected crystallization, vacuum drying is pulverized; With the ginsenoside Rh in the high effective liquid chromatography for measuring crystallization
2And Rg
3Content; This crystallization is and contains the ginsenoside Rh
2And ginsenoside Rg
3The refining thing ginsenoside of antitumor drug; Yield is about 5% of protopanoxadiol saponins inventory.
8, as the application of the arbitrary described pharmaceutical composition of claim 1-4 in preparation medicine for treating tumor thing.
9, the application of pharmaceutical composition as claimed in claim 5 in preparation medicine for treating tumor thing.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104193794A (en) * | 2014-08-07 | 2014-12-10 | 宁波绿之健药业有限公司 | Method for extracting and preparing ginsenoside Rg3 from ginseng |
| CN108295203A (en) * | 2018-02-28 | 2018-07-20 | 延安大学附属医院 | The anticancer usage of Chinese medicine composition |
| CN109432151A (en) * | 2018-12-29 | 2019-03-08 | 金七药业股份有限公司 | Method for improving Radix Notoginseng under ground portion recovery rate |
| CN113082067A (en) * | 2021-04-12 | 2021-07-09 | 北京科莱博医药开发有限责任公司 | Composition for relieving physical fatigue and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100475227C (en) * | 2006-03-21 | 2009-04-08 | 云南天秀植物科技开发有限公司 | Antitumor medicine composition and preparing method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104193794A (en) * | 2014-08-07 | 2014-12-10 | 宁波绿之健药业有限公司 | Method for extracting and preparing ginsenoside Rg3 from ginseng |
| CN108295203A (en) * | 2018-02-28 | 2018-07-20 | 延安大学附属医院 | The anticancer usage of Chinese medicine composition |
| CN109432151A (en) * | 2018-12-29 | 2019-03-08 | 金七药业股份有限公司 | Method for improving Radix Notoginseng under ground portion recovery rate |
| CN113082067A (en) * | 2021-04-12 | 2021-07-09 | 北京科莱博医药开发有限责任公司 | Composition for relieving physical fatigue and application thereof |
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