CN1600317A - Low polarity ginsenoside combination possessing anti-tumor activity - Google Patents

Low polarity ginsenoside combination possessing anti-tumor activity Download PDF

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CN1600317A
CN1600317A CN 03134091 CN03134091A CN1600317A CN 1600317 A CN1600317 A CN 1600317A CN 03134091 CN03134091 CN 03134091 CN 03134091 A CN03134091 A CN 03134091A CN 1600317 A CN1600317 A CN 1600317A
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group
tumor activity
glycol
low polarity
glc
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CN1305479C (en
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杨凌
何克江
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WUHAN DOCAN PHARMACEUTICAL CO Ltd
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Dalian Institute of Chemical Physics of CAS
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Abstract

A low-polarity ginsenoside with high antineoplastic activity for treating tumor is a mixture of the low-polarity ginsenoside groups while have different activities.

Description

Low polarity Panaxsaponin composition with anti-tumor activity
Technical field:
The present invention relates to have the low polarity Panaxsaponin composition of anti-tumor activity, particularly relate to the mixture of any one or more groups low-polar in table 1 glycol I group and all the other six groups of low-polars.Described compositions has inducing tumor cell differentiation, inducing apoptosis of tumour cell, inhibition tumor growth, reverse multiple drug resistance of tumor, suppresses infiltration and anti-tumor activities such as transfer, enhancing human body immunity power and reduction toxic and side that tumor neogenetic blood vessels generated, suppressed tumor.
Background technology:
Radix Ginseng has multiple physiology and pharmacological action, as antitumor, enhance immunity, microcirculation improvement, steadily blood pressure, blood sugar regulation, blood fat reducing, calm the nerves, defying age, antitonic, adjusting digestive function, prevention of digestive tract ulcers, raising quality of life, hypermnesis and learning capacity etc.At anti-tumor aspect, Radix Ginseng has: 1, modulate tumor gene expression of cells and short differentiation; 2, suppress the infiltration and the transfer of tumor; 3, suppress the new vessels generation of tumor inducing; 4, reduce the toxic and side effects of chemotherapeutics; 5, reversing tumor drug resistance, the sensitivity of raising chemotherapeutic, enhancing chemotherapeutic efficacy etc.
The medicinal forms of Radix Ginseng has bright ginseng, Radix Ginseng and Radix Ginseng Rubra, and three's relation is that bright ginseng obtains Radix Ginseng through the room temperature drying, and is Radix Ginseng Rubra through steaming after drying.Use experience and study of pharmacy show that the drug effect of Radix Ginseng Rubra is higher than Radix Ginseng and bright ginseng.Modern study proves that further unique drug effect of Radix Ginseng Rubra has benefited from wherein containing distinctive Rg 2, Rg 3, Rh class, Rk class and natural trace such as polyacetylene compound such as Panaxynol or rare composition.Wherein: the characteristics of C-K are that the new vessels that suppresses tumor inducing forms, soaking of tumor of resistance attacked and shifted; Rg 3Attack, shift for suppressing bullate soaking; Rh 2Be the induced tumor differentiation.The compositions of people and low-polar will be given full play to the characteristics of various low-polars, and active anticancer is significantly strengthened.
Chinese patent CN1187132A discloses the enhanced ginsenoside's compositions of a kind of pharmacologically active, the main component of said composition be the ginsenoside 20-(S, R)-Rg 3, Rg 5, Rk 1, also contain in addition the ginsenoside 20 of the non-glycoside ginsenoside derivant of a great deal of, a small amount of natural ginseng Saponin and trace-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4, Rk 3Under patent CN1187132A condition, most of triol group natural ginseng Saponin is decomposed into non-glycoside derivant, and be converted into low-polar 20-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4And Rk 3Amount very little; And to be converted into unique controllable factor of low polarity Saponin be conversion temperature to the natural ginseng Saponin among the patent CN1187132A, and therefore, the content of each low-polar is uncontrollable in the described compositions of this patent.
The technology contents of invention:
The present invention aims to provide multiple quality controllable low polarity Panaxsaponin composition, to give full play to the characteristics of various low-polars, active anticancer is significantly strengthened.Said composition has multiple anti-tumor activity, as inducing tumor cell differentiation, inducing apoptosis of tumour cell, inhibition tumor growth, reverse multiple drug resistance of tumor, the infiltration that suppresses tumor neogenetic blood vessels generation, inhibition tumor and transfer, enhancing human body immunity power and reduction toxic and side etc.
The invention provides compositions is the mixture that low-polar is organized low-polar more in the table 1.
The grouping of table 1 low-polar
Grouping low-polar production method
I CompundK, Mx enzymatic isolation method (the natural Saponin of glycol group)
II Rg 5, Rk 1Pyrolytic (the natural Saponin of glycol group)
Glycol group III 20-(S)-Rg 3, Rh 2, PPD high temperature alkaline hydrolysis (the natural Saponin of glycol group)
IV 20-(S, R)-Rg 3, Rg 5, Rk 1Acid pyrolysis (the natural Saponin of glycol group)
I 20-(S, R)-Rg 2, Rg 6, F 4Acid pyrolysis (ginsenoside Re)
Triol group II 20-(S, R)-Rh 1, Rh 4, Rk 3Acid pyrolysis (panaxoside Rg 1)
III 20-(S, R)-Rg 2, Rg 6, F 4, acid pyrolysis (the natural Saponin of triol group)
20-(S，R)-Rh 1、Rh 4、Rk 3
Its chemical structural formula is:
??Ginsenoside ??R ????R’ ??R”
?Diol ?type ?Triol ?type ??(20S)Rb 1??(20S)Rb 2??(20S)Rb 3??(20S)Rc ??(20S)Rd ??(20S，R)Rg 3??(20S，R)Rh 2??(20S，R)Rs 3??C-K ??C-Y ??Mx ??Mc ??(20S)Re ??(20S)Rg 1??(20S，R)Rg 2??(20S)Rf ??(20S，R)Rh 1 ??O-Glc 2- 1Glc ??O-Glc 2- 1Glc ??O-Glc 2- 1Glc ??O-Glc 2- 1Glc ??O-Glc 2- 1Glc ??O-Glc 2- 1Glc ??O-Glc ??O-Glc 2- 1Glc-Ac ??OH ??OH ??OH ??OH ??OH ??OH ??OH ??OH ??OH ????H ????H ????H ????H ????H ????H ????H ????H ????H ????H ????H ????H ????O-Glc 2- 1Rha ????O-Glc ????O-Glc 2- 1Rha ????O-Glc 2- 1Glc ????O-Glc ??O-Glc 6- 1Glc ??O-Glc 6- 1Arap ??O-Glc 6- 1Xyl ??O-Glc 6- 1Araf ??O-Glc ??OH ??OH ??OH ??O-Glc ??O-Glc 6- 1Arap ??O-Glc 6- 1Xyl ??O-Glc 6- 1Araf ??O-Glc ??O-Glc ??OH ??O-Glc ??OH
Glc：β-D-glucopyranosyl；Arap：α-L-arabinopyranosyl；
Xyl：β-D-xylopyranosyl；Araf：α-D-arabinofuranosyl；
Rha：-L-rhamnopyranosyl；Ac：6’-O-Acetyl.
Ginsenoside???????????R?????????????????R’???????????????????????Ginsenoside?????????????R???????????????R’
Rg 5???????O-Glc 2- 1Glc?????H?????????????????Rk 1????????????O-Glc 2- 1Glc?????H
Diol??????Rh 3???????O-Glc??????????????H?????????????????Rk 2????????????O-Glc?????????????H
Type??????Rs 4???????O-Glc 2- 1Glc-Ac??H?????????????????Rs 5????????????O-Glc 2- 1Glc-Ac??H
F 4????????OH?????????????????O-Glc 2- 1Rha????Rg 6????????????OH?????????????????O-Glc 2- 1Rha
Triol?????Rh 4???????OH?????????????????O-Glc?????????????Rk 3????????????OH?????????????????O-Glc
Type??????Rs 6???????OH?????????????????O-Glc-Ac??????????Rs 1????????????OH?????????????????O-Glc-Ac
The present invention specifically provides following compositions, it is characterized in that the mixture of described compositions for any one or more groups low-polar in glycol I group (Compund K and Mx) and the following six groups of low-polars:
Glycol II group: Rg 5, Rk 1,
Glycol III group: 20-(S)-Rg 3, Rh 2, PPD,
Glycol IV group: 20-(S, R)-Rg 3, Rg 5, Rk 1
Triol I group: 20-(S, R)-Rg 2, Rg 6, F 4,
Triol II group: 20-(S, R)-Rh 1, Rh 4, Rk 3,
Triol III group: 20-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4, Rk 3
In the compositions with anti-tumor activity provided by the present invention, glycol I group proportion is 20%～90%, and accumulated dose is counted 1-50mg/Kg/ days with the effective ingredient low-polar.
Compositions with anti-tumor activity provided by the present invention can be made the preparation of various pharmaceutical dosage forms with any officinal with compounding ingredient and excipient.
Composite preparation with anti-tumor activity provided by the present invention can use separately, also can unite use, or be prepared into compound preparation and use with in the market any chemotherapeutic (comprise hormones, alkylating agent class, platinum class, anti-metabolism, topoisomerase enzyme inhibitor class, anti-microfilament microtubule class, induce differentiation class and other).
That composite preparation dosage form with anti-tumor activity provided by the present invention can be is oral, injection or local application's dosage form.
In the composite preparation with anti-tumor activity provided by the present invention, peroral dosage form can be tablet, powder, suspension, emulsion, capsule, granule, coated tablet, pill, liquid, spirit, syrup or limonada etc.
In the composite preparation with anti-tumor activity provided by the present invention, injection type can be water preparation, suspension or solution etc.
In the composite preparation with anti-tumor activity provided by the present invention, local application's dosage form can be ointment, solid, suspension, water preparation, spirit, powder, paste, suppository, aerosol, paste, liniment, lotion, enema or Emulsion etc.
In the composite preparation with anti-tumor activity provided by the present invention, excipient can be one or more in following: (a) the powdery excipient of peroral dosage form such as lactose, crystalline cellulose, starch, dextrin, calcium phosphate, calcium carbonate, synthetic or natural aluminium dioxide, exsiccant aluminium hydroxide, magnesium stearate, sodium bicarbonate and surfactant such as phospholipid, cholic acid, Cremorphor, polysorbate (Tween) 80, PluronicL64 and poloxamor etc.; (b) the powdery excipient of local application's dosage form such as zinc oxide, Talcum, starch, high potter's clay, borate powder, zinc stearate, magnesium stearate, magnesium carbonate, winnofil, bismuth subgallate, aluminum potassium sulfate powder and surfactant such as phospholipid, cholic acid, Cremorphor, polysorbate (Tween) 80, Pluronic L64 and poloxamor or the like; (c) liquid usefulness excipient such as water, glycerol, propylene glycol, sweet taste syrup, ethanol, fatty oil, Ethylene Glycol, Polyethylene Glycol, sorbitol; The ointment excipient, as mixing-in fat, fatty oil, lanoline, vaseline, glycerol, wax, Japan wax, paraffin, sulphuric acid paraffin, resin, higher alcohol, plastics, ethylene glycol, water or surfactant (comprise liposoluble base, water-soluble base and the base that suspends, as with surfactant such as phospholipid, cholic acid, Cremorphor, polysorbate (Tween) 80, Pluronic L64 and poloxamor) etc.
The specific embodiment:
One, the preparation of low-polar
Embodiment 1: glycol I group: the preparation of Compund K and Mx
Glycol group stem and leaf of Radix Notoginseng Saponin (25g) is dissolved in 32mL phosphoric acid-citrate buffer solution with Snailase (84mg) enzyme, and (pH4.5, ionic strength is 0.001molL -1, contain 10% ethanol) in, hydrolysis is 1 day in 40 ℃ of water-baths; Centrifugal reaction solution, collecting precipitation, water is made suspension with precipitate, ethyl acetate extraction (10mL * 5) suspension, combined ethyl acetate liquid, decompression obtains C-K and Mx mixture (12.6g, ginsenoside's total content＞95%) after removing ethyl acetate.
Embodiment 2: glycol II group: Rg 5And Rk 1Preparation
25g panoxadiol type saponin is dissolved in the 100ml positive butanols and (contains benzoyl peroxide 0.5g), under 180 ℃ of temperature (about 0.15MPa), nitrogen protection condition, stirs degraded 5h; Reactant liquor obtains Rg after neutralization (2mol/LHCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam n-butyl alcohol 5And Rk 1Mixture (13.4g, ginsenoside's total content＞95%).
Embodiment 3: glycol III group: 20-(S)-Rg 3, Rh 2Preparation with PPD
25g panoxadiol type saponin is dissolved in the 100ml alkalescence positive butanols (containing metal sodium 0.5g, benzoyl peroxide 0.5g), under 180 ℃ of temperature (about 0.15MPa), nitrogen protection condition, stirs degraded 5h; Reactant liquor obtains 20-(S)-Rg after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam n-butyl alcohol 3, Rh 2With PPD mixture (13.4g, ginsenoside's total content＞95%).
Embodiment 4: and glycol IV group: 20-(S, R)-Rg 3, Rg 5And Rk 1Preparation
Diol type ginsenoside (25g) is soaked mixing with 45% malonic acid aqueous solution (5ml), places high-pressure sterilizing pot, 120 ℃ of pyrolysis 5 hours.(HPLC the analysis showed that thermal decomposition product, and pyrolysis conversion ratio 〉=96%, principal product are 20-(R)-Rg 3, 20-(S)-Rg 3, Rg 5And Rk 1) in, add the 100mL aqueous solution and form suspension, with dichloromethane extraction 3 times, after the aqueous phase dichloromethane is removed in decompression, again to the ethanol 1000ml that wherein adds 30%, lysate is carried out the adsorbent resin column chromatography, and after 30% the ethanol elution remove impurity, the ethanol elution with 90% reclaims low polarity saponin.Concentrating under reduced pressure, evaporate to dryness, obtain 20-(S, R)-Rg 3, Rg 5And Rk 1Mixture (13.3g, ginsenoside's total content＞95%).
Embodiment 5: and triol I group: 20-(S, R)-Rg 2, Rg 6And F 4Preparation
Ginsenoside Re (25g) and 45% gallic acid aqueous solution (5ml) soak mixing, place high-pressure sterilizing pot, 120 ℃ of pyrolysis 5 hours.Thermal decomposition product (HPLC the analysis showed that, pyrolysis conversion ratio 〉=96%, principal product be 20-(S, R)-Rg 2, Rg 6And F 4) in, add the 100mL aqueous solution and form suspension, with dichloromethane extraction 3 times, after the aqueous phase dichloromethane is removed in decompression, again to the ethanol 1000ml that wherein adds 30%, lysate is carried out the adsorbent resin column chromatography, and after 30% the ethanol elution remove impurity, the ethanol elution with 90% reclaims low polarity saponin.Concentrating under reduced pressure, evaporate to dryness, obtain 20-(S, R)-Rg 2, Rg 6And F 4(13.5g, ginsenoside's total content＞95%).
Embodiment 6: and triol II group: 20-(S, R)-Rh 1, Rh 4And Rk 3Preparation
The ginsenoside Rg 1(25g) soak mixing, place high-pressure sterilizing pot, 120 ℃ of pyrolysis 5 hours with 45% gallic acid aqueous solution (5ml).Thermal decomposition product (HPLC the analysis showed that, pyrolysis conversion ratio 〉=96%, principal product be 20-(S, R)-Rh 1, Rh 4And Rk 3) in, add the 100mL aqueous solution and form suspension, with dichloromethane extraction 3 times, after the aqueous phase dichloromethane is removed in decompression, again to the ethanol 1000ml that wherein adds 30%, lysate is carried out the adsorbent resin column chromatography, and after 30% the ethanol elution remove impurity, the ethanol elution with 90% reclaims low polarity saponin.Concentrating under reduced pressure, evaporate to dryness, obtain 20-(S, R)-Rh 1, Rh 4And Rk 3(13.1g, ginsenoside's total content＞95%).
Embodiment 7: and triol II group: 20-(S, R)-Rh 1, Rh 4And Rk 3Preparation
Triol type ginsenoside (25g) and 45% malonic acid aqueous solution (5ml) soak mixing, place high-pressure sterilizing pot, 120 ℃ of pyrolysis 5 hours.Thermal decomposition product (HPLC the analysis showed that, pyrolysis conversion ratio 〉=96%, principal product be 20-(S, R)-Rh 1, Rh 4And Rk 3) in, add the 100mL aqueous solution and form suspension, with dichloromethane extraction 3 times, after the aqueous phase dichloromethane is removed in decompression, again to the ethanol 1000ml that wherein adds 30%, lysate is carried out the adsorbent resin column chromatography, and after 30% the ethanol elution remove impurity, the ethanol elution with 90% reclaims low polarity saponin.Concentrating under reduced pressure, evaporate to dryness, obtain 20-(S, R)-Rh 1, Rh 4And Rk 3(13.2g, ginsenoside's total content＞95%).
Embodiment 8: and triol III group: 20-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4And Rk 3Preparation
Triol type ginsenoside (25g) and 45% aspartic acid aqueous solution (5ml) soak mixing, place high-pressure sterilizing pot, 120 ℃ of pyrolysis 5 hours.(HPLC the analysis showed that thermal decomposition product, and pyrolysis conversion ratio 〉=96%, principal product are 20 (R)-Rg 2, 20 (S)-Rg 2, Rg 6, F 4, 20-(R)-Rh 1, 20-(S)-Rh 1, Rh 4And Rk 3) in, add the 100mL aqueous solution and form suspension, with dichloromethane extraction 3 times, after the aqueous phase dichloromethane is removed in decompression, again to the ethanol 1000ml that wherein adds 30%, lysate is carried out the adsorbent resin column chromatography, and after 30% the ethanol elution remove impurity, the ethanol elution with 90% reclaims low polarity saponin.Concentrating under reduced pressure, evaporate to dryness, obtain 20-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4And Rk 3Mixture (13.5g, ginsenoside's total content＞95%).
Two, preparation
Embodiment 9: the tablet formulation example
Low-polar glycol I, II, IV and triol III organize the mixture uniform mixing of (respectively accounting for 25%) and lactose, crystalline cellulose and 1% cholate, make the tablet of every 200mg through tablet machine.
Embodiment 10: the injection formulation examples
Under the sterile working, the ethanol solution of low-polar glycol I, II, IV and triol III being organized (respectively accounting for 25%) and equivalent Cremorphor pours into the peace bottle, obtains the injection preparation of 200mg/ bottle.
Embodiment 11: the tablet formulation example
Low-polar glycol I and triol III organize the mixture uniform mixing of (respectively accounting for 50%) and lactose, crystalline cellulose and 1% cholate, make the tablet of every 200mg through tablet machine.
Embodiment 12: the tablet formulation example
Low-polar glycol I, II and triol III organize the mixture uniform mixing of (respectively accounting for 33%) and lactose, crystalline cellulose and 1% cholate, make the tablet of every 200mg through tablet machine.
Embodiment 13: the tablet formulation example
Low-polar glycol I, IV and triol III organize the mixture uniform mixing of (respectively accounting for 33%) and lactose, crystalline cellulose and 1% cholate, make the tablet of every 200mg through tablet machine.
Three, biological activity
Embodiment 14: the activity that suppresses the growth of MCF-7 and K562 cell
A), method: with human breast carcinoma MCF-7 cell strain and human erythroleukemia K562 cell strain serves as that experiment is used cell strain, the trophophase cell (2.5 * 10 of taking the logarithm 5/ mL) being seeded in 96 orifice plates, concentration adds drug solution from high to low, and matched group then adds equal-volume RPM RPMI-1640.Behind the drug effect 48 hours, by mtt assay seek survival long suppression ratio and IC 50:
Growth inhibition ratio (%)=[1-experimental group OD value/matched group OD value] * 100%
IC 50Be that growth inhibition ratio is 50% o'clock a drug level.
B), experimental result: as shown in table 1.
Table 1. suppresses MCF-7 and K562 cells growth activity
IC 50(μg)
MCF-7??????????????????K562
ADM??????????????????1.4±0.1???????????????2.6±0.2
Glycol I group 13.5 ± 1.7 22.0 ± 1.8
Glycol II group 15.5 ± 1.9 25.0 ± 2.0
Glycol III group 14.5 ± 1.7 20.0 ± 2.2
Glycol IV group 15.8 ± 2.7 26.0 ± 2.4
Triol I group 26.2 ± 1.2 36.5 ± 1.1
Triol II group 29.7 ± 1.4 34.5 ± 1.6
Triol III group 25.3 ± 1.8 34.2 ± 2.1
Annotate: the molecular weight of low-polar is in mean molecule quantity 710.
Embodiment 15: suppress the activity that the Lewis lung cancer lung shifts
A), method: the C57BL/6 in 8 ages in week is not had tumor mice random packet, 2 all oral administration Radix Ginseng total saponins, 5-Fu, embodiment 9 tablets and normal saline (10mg/Kg/d respectively before and after the inoculated tumour cell, 5 times/d), and abdominal cavity inoculation Lewis lung cancer cell (0.2ml/, 5 * 10 5Individual cell/ml) is put to death mice after two weeks, gets the lungs malingering and separates, and calculates lung metastasis quantity, represents active height with the metastasis inhibition percentage rate.
Metastasis inhibition rate (%)=[(matched group lung metastasis number-experimental group lung metastasis number)/matched group lung metastasis number] * 100%
B), the lung metastasis inhibition rate of experimental result: embodiment 9 tablets is 60%, is higher than 5-Fu group (40%) and Radix Ginseng total saponins group (10%).
Embodiment 13: reverse multiple drug resistance of tumor
A), method: with human breast carcinoma amycin persister MCF-7/ADM and sensitive strain MCF-7/S thereof and human erythroleukemia amycin persister K562/A and sensitive strain K562/S thereof serve as experiment with cell strain (with the IC of sensitive cells strain 50Be radix, drug-resistant cell strain is 30 times to the drug resistance multiple MCF-7 of amycin, and K562 is 62 times), with mtt assay investigate chemical compound under nontoxic or low toxicity dosage chemical compound to amycin IC 50(amycin persister) influence is calculated the drug resistance multiple according to following formula.
Drug resistance multiple=mdr cell IC 50/ sensitive cells IC 50
B), experimental result: as shown in table 1
Table 2. reverse multiple drug resistance of tumor activity
The concentration cell is given birth to rate (%) drug resistance multiple
(μM)??????MCF-7/A???????K562/A???????MCF-7/A???????K562/A
control???????????????????100???????????98???????????30.1??????????62.5
Verapamil??????10?????????100???????????95???????????7.8???????????6.9
Glycol I organizes 5 90 84 7.3 0.9
Glycol II organizes 5 94 95 6.2 4.1
Glycol III organizes 5 94 85 9.6 6.3
Glycol IV organizes 5 94 85 7.7 5.5
Triol I organizes 5 90 85 15.9 10.5
Triol II organizes 5 90 85 16.0 11.0
Triol III organizes 5 90 85 14.8 9.6
Annotate: the molecular weight of low-polar is in mean molecule quantity 710.

Claims (8)

1, a kind of low polarity Panaxsaponin composition with anti-tumor activity is characterized in that the mixture of described compositions for any one or more groups low-polar in glycol I group Compund K and Mx and the following six groups of low-polars:
Glycol II group: Rg 5, Rk 1,
Glycol III group: 20-(S)-Rg 3, Rh 2, PPD,
Glycol IV group: 20-(S, R)-Rg 3, Rg 5, Rk 1
Triol I group: 20-(S, R)-Rg 2, Rg 6, F 4,
Triol II group: 20-(S, R)-Rh 1, Rh 4, Rk 3,
Triol III group: 20-(S, R)-Rg 2, Rg 6, F 4, 20-(S, R)-Rh 1, Rh 4, Rk 3
2, according to the described low polarity Panaxsaponin composition of claim 1 with anti-tumor activity, it is characterized in that: in the described compositions, glycol I group proportion is 20%～90%, and accumulated dose is counted 1-50mg/Kg/ days with the effective ingredient low-polar.
3, according to claim 1 or 2 described low polarity Panaxsaponin compositions with anti-tumor activity, it is characterized in that: compositions can be made the preparation of various pharmaceutical dosage forms with any officinal with compounding ingredient and excipient.
4, according to the described low polarity Panaxsaponin composition of claim 3 with anti-tumor activity, it is characterized in that: compositions can with any chemotherapeutic in the market, comprise hormones, alkylating agent class, platinum class, anti-metabolism, topoisomerase enzyme inhibitor class, anti-microfilament microtubule class, induce differentiation class and other, be prepared into compound preparation.
5, according to the described low polarity Panaxsaponin composition with anti-tumor activity of claim 4, it is characterized in that: described dosage form is any of oral, injection or local application's dosage form.
6, according to the described low polarity Panaxsaponin composition with anti-tumor activity of claim 4, it is characterized in that: described peroral dosage form comprises tablet, powder, suspension, emulsion, capsule, granule, coated tablet, pill, liquid, spirit, syrup and limonada.
7, according to the described low polarity Panaxsaponin composition with anti-tumor activity of claim 4, it is characterized in that: described injection type comprises water preparation, suspension, liposome and solution.
8, according to the described low polarity Panaxsaponin composition with anti-tumor activity of claim 4, it is characterized in that: described local application dosage form comprises ointment, solid, suspension, water preparation, spirit, powder, paste, suppository, aerosol, paste, liniment, lotion, enema and Emulsion.
CNB031340911A 2003-09-28 2003-09-28 Low polarity ginsenoside combination possessing anti-tumor activity Expired - Fee Related CN1305479C (en)

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CN105017369A (en) * 2015-07-21 2015-11-04 吉林农业大学 Thermal cracked ginsenoside composition preparation method and novel use of thermal cracked ginsenoside composition in preparation of antitumor drugs
CN106109483A (en) * 2016-07-29 2016-11-16 陕西巨子生物技术有限公司 There is the glycol group/triol group rare ginsenoside compositions of anti-tumor activity

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CN1167805C (en) * 2001-11-06 2004-09-22 中国科学院大连化学物理研究所 Ginsenoside enzymatically hydrolyzing process to prepare 2o-beta-D-pyranoglucose protopanoxadiol

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CN100337636C (en) * 2005-07-14 2007-09-19 中国医药研究开发中心有限公司 Medicinal composition contg. ginseng secondary glycosides, prepn. method and application thereof
CN102125574A (en) * 2011-01-26 2011-07-20 吉林大学 Medicinal composition for suppressing tumors
CN105017369A (en) * 2015-07-21 2015-11-04 吉林农业大学 Thermal cracked ginsenoside composition preparation method and novel use of thermal cracked ginsenoside composition in preparation of antitumor drugs
CN106109483A (en) * 2016-07-29 2016-11-16 陕西巨子生物技术有限公司 There is the glycol group/triol group rare ginsenoside compositions of anti-tumor activity
CN106109483B (en) * 2016-07-29 2020-02-07 陕西巨子生物技术有限公司 Diol/triol rare ginsenoside composition with anti-tumor activity

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