CN102397398A - Traditional Chinese medicine composition for reversing tumor multidrug resistance and preparation method and application thereof - Google Patents
Traditional Chinese medicine composition for reversing tumor multidrug resistance and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for reversing tumor multidrug resistance, and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 10-30 parts of subprostrate sophora, 10-30 parts of solanum lyratum, 10-30 parts of broadleaf holly leaf, 10-30 parts of Chinese arborvitae leaf and 10-30 parts of leaf flower; mixing the traditional Chinese medicine raw materials in parts by weight, adding water, soaking for 2-3 hours, heating and decocting, pouring out decoction, adding water, heating and decocting, pouring out the decoction, combining the decoctions, filtering, concentrating, spray drying, crushing and sieving the obtained clear liquid to obtain the traditional Chinese medicine composition for reversing the multidrug resistance of the tumors. The serum of the traditional Chinese medicine composition is combined with adriamycin to ensure that the half inhibitory concentration of the adriamycin to a leukemia cell adriamycin-resistant strain is obviously reduced, the reversion multiple is 2.87-4.37, the concentration is positively correlated, and the traditional Chinese medicine composition has an obvious effect of reversing the multidrug resistance of tumors.
Description
Technical field
The invention belongs to the field of Chinese medicines, relate to a kind of Chinese medicine composition of reverse multiple drug resistance of tumor.
Technical background
(multidrug resistance MDR) is the common factor that causes tumor chemotherapy failure to tumor cell to the multidrug resistance of antitumor drug.Present domestic tumor prevalence is in rising trend, and therefore the death of 90% tumor patient need development reversal agent of drug resistance of new generation in the influence that receives drug resistance of tumor cell in varying degrees.Known some Chinese medicine has calcium antagonism, and drug effect is gentle, and can in reversion MDR, improve chemotherapy effect, has good application and DEVELOPMENT PROSPECT.
Result of study shows that number of mechanisms participation tumor cell multidrug resistance forms; Mainly comprise: cell membrane P-glycoprotein (Permeability-glycoprotein; P-gP), MRP (Multidrug Resistance Associated Protein; MRP) overexpression forms the medicine output pump, makes cancer therapy drug in tumor cell, accumulate decline; Glutathione-S-transferase (GST) is participated in various kinds of cell poison metabolism and detoxification processes separately or with glutathion (GSH); The factor relevant and gene such as bcl-2 with apoptosis, P
53Deng unusual.Carried out broad research to seek the medicine of antagonism and/or reversing tumor cell MDR to above-mentioned link both at home and abroad; External be proved have the active chemical compound of reversing drug resistance or biological preparation a lot; But what really get into clinical research has only only a fews such as isoptin, cyclosporin A, and curative effect is undesirable.Also do not have a kind of medicine or method to be widely accepted clinical at present, reason is: existing inversion agent is " old medicine is newly used " mostly, and reversing drug resistance often is not its major function, and clinical use contraindication is many, and toxic and side effects is big; Biological preparation is unstable in vivo, is difficult to affact target spot and toxicity is many; Clinical drug-resistant often several mechanisms is participated in simultaneously, only the acting inversion agent of single mechanism is difficult to bring into play significant effect.Wherein for Chinese medicine or effective monomer component research, really can combine the research of clinical efficacy and theory of Chinese medical science rare.
Say pharmaceutically that therefrom the collaborative chemotherapeutic treatment malignant tumor research of Chinese medicine expands to " anticancer enhanced sensitivity attenuation " from " setting upright " " efficacy enhancing and toxicity reducing ", and clearly proposes the Comprehensive Treatment notion of Chinese medicine; If certain Chinese medicine through the clinical observation determined curative effect; It had both played the reversion MDR activity, can embody active anticancer again, and double effect organically combines; It will be become near ideal tumor drug resistance reversal agent, embody efficient, low toxicity, target spot characteristics widely.
Chinese invention patent CN200710070320.4 discloses " purposes of curcumin in the preparation tumor multi-medicine drug-resistant prevention agent ", and Chinese invention patent CN200710143393.1 discloses " application of arteannuin in the preparation artitumor multi-medicine-resistant medicine "; But the report of at present relevant Chinese medicine composition as multidrug resistance reversing agent is less.
Summary of the invention
In order to overcome the deficiency of above prior art, primary and foremost purpose of the present invention provides a kind of Chinese medicine composition of reverse multiple drug resistance of tumor.
Another object of the present invention provides the method for preparing of above-mentioned reverse multiple drug resistance of tumor Chinese medicine composition.
The present invention also aims to provide the application of the Chinese medicine composition of above-mentioned reverse multiple drug resistance of tumor.
The object of the invention is realized through following technical scheme:
A kind of Chinese medicine composition of reverse multiple drug resistance of tumor is prepared from the following raw material of Chinese medicine of meter by weight: 10～30 parts of Radix Sophorae Tonkinensiss, 10～30 parts of Herba Solani Lyratis, 10～30 parts of Folium Ilicis, 10～30 parts on side one hundred leaf, 10～30 parts of Flos Bougainvillea Glabraes.
Preferably, the Chinese medicine composition of above-mentioned reverse multiple drug resistance of tumor is prepared from the following raw material of Chinese medicine of meter by weight: 12 parts of Radix Sophorae Tonkinensiss, 12 parts of Herba Solani Lyratis, 18 parts of Folium Ilicis, 12 parts on side one hundred leaf, 18 parts of Flos Bougainvillea Glabraes.
The method for preparing of the Chinese medicine composition of said reverse multiple drug resistance of tumor comprises the steps:
(1) with Radix Sophorae Tonkinensis 10～30 weight portion; Herba Solani Lyrati 10～30 weight portions, Folium Ilicis 10～30 weight portions, side one hundred leaf 10～30 weight portions with add 9～10 times of water gagings of each raw material of Chinese medicine gross weight after Flos Bougainvillea Glabrae 10～30 weight portions mix and soaked 2～3 hours; Heating decocted 1.5～2 hours, and inclining decoction liquor; Medicinal residues add 8～9 times of water gaging heating of each raw material of Chinese medicine gross weight again and decocted 1～1.5 hour, and inclining decoction liquor, and the decoction liquor that twice decoction obtained merges filtration, obtains clear liquid;
(2) clear liquid being concentrated into relative density is to carry out spray drying after 1.05～1.06, obtains spray drying powder; It is 30～100 orders that spray drying powder is crushed to fineness, obtains the Chinese medicine composition of reverse multiple drug resistance of tumor.
Spray drying condition in the said step (2) is: EAT is 140～160 ℃, and leaving air temp is 100～110 ℃, 50～60 rev/mins of nebulizer rotating speeds, and charging rate is 3～5ml/ minute.
Above-mentioned Chinese medicine composition can be used for preparing the medicine of reverse multiple drug resistance of tumor.
The effect of the raw material of Chinese medicine that the present invention uses is following:
Radix Sophorae Tonkinensis: bitter in the mouth, cold in nature; Poisonous; Attach to the lung and stomach meridians;
Herba Solani Lyrati: bitter in the mouth, cold nature; Slightly poisonous; Go into liver, stomach warp;
Folium Ilicis: sweet in the mouth, hardship; Cold in nature; Return liver; Lung; The stomach warp;
Side one hundred leaf: bitter in the mouth, puckery, cold in nature; Return lung, liver, spleen channel;
Flos Bougainvillea Glabrae: nature and flavor are bitter, and are puckery; Warm in nature; Return Liver Channel;
The present invention adopts various raw material of Chinese medicine compatibilities, plays heat-clearing toxin-expelling functions, is applied in the tumor multi-medicine drug-resistant patient treatment, can produce the effect of reverse multiple drug resistance of tumor, and this Chinese medicine composition has no side effect, and plays the beneficial effect that improves chemotherapeutical medicine curative effect.
Compared with prior art, the present invention has following beneficial effect:
Experimentation shows that the serum of Chinese medicine composition of the present invention and amycin are united use can make the half-inhibition concentration IC of amycin to leukaemia's amycin persister
50Obviously descend, different dosing concentration is 2.87～4.37 to the reverse multiple of leukaemia's amycin persister, and is the concentration positive correlation, has the effect of significant reverse multiple drug resistance of tumor.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail, but embodiment of the present invention is not limited thereto.
Embodiment 1
The preparation of the Chinese medicine composition of reverse multiple drug resistance of tumor:
(1) take by weighing Radix Sophorae Tonkinensis 100g, Herba Solani Lyrati 300g, Folium Ilicis 100g, side one hundred leaf 300g and Flos Bougainvillea Glabrae 100g add 9 times of water gagings of each raw material of Chinese medicine gross weight and soaked 2 hours after the mixing, and heating decocts 1.5h, and inclining decoction liquor; Medicinal residues add 8 times of water gaging heating of each raw material of Chinese medicine gross weight again and decoct 1.5h, and inclining decoction liquor, and the decoction liquor that twice decoction obtained merges filtration, obtains clear liquid;
(2) clear liquid being concentrated into relative density is 1.05 o'clock, sends into spray dryer and carries out spray drying, and EAT is controlled to be 140 ℃, and leaving air temp is 100 ℃, 50 rev/mins of nebulizer rotating speeds, and charging rate is 3ml/ minute, gets spray drying powder 30 grams; It is 100 orders that spray drying powder is crushed to fineness, obtains the Chinese medicine composition of reverse multiple drug resistance of tumor.
Embodiment 2
The preparation of the Chinese medicine composition of reverse multiple drug resistance of tumor:
(1) take by weighing raw material of Chinese medicine Radix Sophorae Tonkinensis 300g, Herba Solani Lyrati 100g, Folium Ilicis 300g, side one hundred leaf 100g and Flos Bougainvillea Glabrae 300g add 10 times of water gagings of each raw material of Chinese medicine gross weight and soaked 3 hours after the mixing, and heating decocts 2h, and inclining decoction liquor; Medicinal residues add 8 times of water gaging heating of each raw material of Chinese medicine gross weight again and decoct 1h, and inclining decoction liquor, and the decoction liquor that twice decoction obtained merges filtration, obtains clear liquid;
(2) to be concentrated into relative density be 1.05 o'clock to clear liquid, advances spray dryer, 140 ℃ of EAT controls, 100 ℃ of leaving air temps, 50 rev/mins of nebulizer rotating speeds, charging rate is 3ml/ minute, spray drying powder 50 grams; It is 80 orders that spray drying powder is crushed to fineness, obtains the Chinese medicine composition of reverse multiple drug resistance of tumor.
Embodiment 3
The preparation of the Chinese medicine composition of reverse multiple drug resistance of tumor:
(1) take by weighing raw material of Chinese medicine Radix Sophorae Tonkinensis 120g, Herba Solani Lyrati 120g, Folium Ilicis 180g, side one hundred leaf 120g, Flos Bougainvillea Glabrae 180g adds 9.5 times of water gagings of each raw material of Chinese medicine gross weight and soaked 2.5 hours after the mixing, and heating decocts 2h, and inclining decoction liquor; Medicinal residues add 9 times of water gaging heating of each raw material of Chinese medicine gross weight 1h again, and inclining decoction liquor, and the decoction liquor that twice decoction obtained merges filtration, obtains clear liquid;
(2) to be concentrated into relative density be 1.06 o'clock to clear liquid, advances spray dryer, 160 ℃ of EAT controls, 110 ℃ of leaving air temps, 60 rev/mins of nebulizer rotating speeds, charging rate is 5ml/ minute, spray drying powder 30 grams; It is 30 orders that spray drying powder is crushed to fineness, obtains the Chinese medicine composition of reverse multiple drug resistance of tumor.
Embodiment 4
It is following that the Chinese medicine composition of embodiment 1 preparation is used to reverse the chemical sproof experimental result of multiple medicine-resistant cell line K562/ADR:
Amycin is a kind of AGPM, can suppress the synthetic of RNA and DNA, and is the strongest to the inhibitory action of RNA, and kinds of tumors is all had effect, belongs to cell cycle nonspecific agent (CCNSA), and the tumor cell of various growth cycles is all had killing action.
Leukaemia K562/S is a sensitive strain in the present embodiment, and K562/ADR is leukaemia's amycin persister, and wherein K562/ADR is induced by the amycin (ADR) of K562/S cells contacting progressive concentration to form, and has typical multidrug resistance.Cell strain all is incubated in the RPMI-1640 culture fluid that contains 10% calf serum.
The pastille serum preparation: NIH mice adaptability was raised after 3 days, weighed, and was divided into totally 4 groups of high dose group, middle dose groups, low dose group, blank control group, 10 every group at random according to random numbers table; The mice of high dose group is by this Chinese medicine composition 40g/kg gastric infusion, and middle dose groups is pressed the 20g/kg gastric infusion, and low dose group is pressed the 10g/kg gastric infusion; The blank group is irritated stomach with normal saline; Behind the administration 2h, get blood centrifugalize serum, 56 ℃ of 30min deactivations are with the serum culture fluid of RPMI-1640 preparation variable concentrations.
The MTT of reversing drug resistance detects:
The trophophase cell of taking the logarithm, the K562/ADR cell is with 1 * 10
5/ ml, K562/S are with 0.5 * 10
5The concentration of/ml is inoculated in 96 well culture plates respectively, 100 μ l/ holes.At 37 ℃ and 5%CO
2Under the condition after the overnight incubation, pastille serum and the ADR that adds variable concentrations be totally 100 μ l, and blank control group adds the culture fluid of respective volume, establishes 4 parallel holes for every group.After cultivating 72h, every hole adds 5mg/ml tetrazolium bromide (MTT) 20 μ l, cultivates 4h again, and the culture fluid that inclines adds dimethyl sulfoxide (DMSO) 100 μ l/ holes, after treating to dissolve fully, after the zeroing of wavelength 570nm place blank control group, reads absorbance (A) value with the enzyme linked immunological appearance; Get the mean of 4 hole A values, obtain half-inhibition concentration (IC
50, cell inhibitory rate is 50% o'clock a drug level); Reverse multiple=blank control group IC
50/ test group IC
50
The Chinese medicine composition of table 1 embodiment 1 preparation is to the reverse effect of K562/ADR persister
Visible by table 1 data, the serum and the ADR that contain Chinese medicine composition of the present invention unite use can make the IC of ADR to K562/ADR
50Obviously descend, it is 2.87～4.37 that different dosing concentration reverses multiple to K562/ADR, and is the concentration positive correlation, shows that Chinese medicine composition of the present invention has reverse effect to the K562/ADR persister.
The foregoing description is a preferred implementation of the present invention; But embodiment of the present invention is not restricted to the described embodiments; Other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; All should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (5)
1. the Chinese medicine composition of a reverse multiple drug resistance of tumor; It is characterized in that: this Chinese medicine composition is prepared from the following raw material of Chinese medicine of meter by weight: 10～30 parts of Radix Sophorae Tonkinensiss, 10～30 parts of Herba Solani Lyratis, 10～30 parts of Folium Ilicis; 10～30 parts on side one hundred leaf, 10～30 parts of Flos Bougainvillea Glabraes.
2. the Chinese medicine composition of a kind of reverse multiple drug resistance of tumor according to claim 1; It is characterized in that: this Chinese medicine composition is prepared from the following raw material of Chinese medicine of meter by weight: 12 parts of Radix Sophorae Tonkinensiss, 12 parts of Herba Solani Lyratis, 18 parts of Folium Ilicis; 12 parts on side one hundred leaf, 18 parts of Flos Bougainvillea Glabraes.
3. the method for preparing of the Chinese medicine composition of reverse multiple drug resistance of tumor according to claim 1 is characterized in that comprising the steps:
(1) with Radix Sophorae Tonkinensis 10～30 weight portion; Herba Solani Lyrati 10～30 weight portions; Folium Ilicis 10～30 weight portions; Side one hundred leaf 10～30 weight portions mix the water logging of 9～10 times of amounts of back each raw material of Chinese medicine gross weight of adding and steeped 2～3 hours with Flos Bougainvillea Glabrae 10～30 weight portions, heating decocted 1.5～2 hours, and inclining decoction liquor; The water heating that medicinal residues add 8～9 times of amounts of each raw material of Chinese medicine gross weight again decocted 1～1.5 hour, and inclining decoction liquor, and the decoction liquor that twice decoction obtained merges filtration, obtains clear liquid;
(2) clear liquid being concentrated into relative density is to carry out spray drying after 1.05～1.06, obtains spray drying powder; It is 30～100 orders that spray drying powder is crushed to fineness, obtains the Chinese medicine composition of reverse multiple drug resistance of tumor.
4. according to the method for preparing of the Chinese medicine composition of the said reverse multiple drug resistance of tumor of claim 3; It is characterized in that: the spray drying condition in the said step (2) is: EAT is 140～160 ℃; Leaving air temp is 100～110 ℃; 50～60 rev/mins of nebulizer rotating speeds, charging rate are 3～5ml/ minute.
5. the application of Chinese medicine composition according to claim 1 and 2 in preparation reverse multiple drug resistance of tumor medicine.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104381541A (en) * | 2014-11-27 | 2015-03-04 | 常熟市海虞茶叶有限公司 | Anticancer tea |
| CN106138726A (en) * | 2016-07-29 | 2016-11-23 | 广州加原医药科技有限公司 | A kind of Chinese medicine composition of reverse multiple drug resistance of tumor |
| CN106309545A (en) * | 2016-08-01 | 2017-01-11 | 广州加原医药科技有限公司 | Chinese medicinal composition for reversing tumor multidrug resistance (MDR) and preparation method thereof |
| CN108186923A (en) * | 2018-02-02 | 2018-06-22 | 广州国宇医药科技有限公司 | A kind of Chinese medicine oat seaweed sugar composite and preparation method thereof |
| CN112138066A (en) * | 2020-09-09 | 2020-12-29 | 中南大学湘雅医院 | Application of black nightshade or black nightshade extract in increasing antibiotic or antineoplastic drug sensitivity |
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| CN1260983A (en) * | 1999-01-21 | 2000-07-26 | 仇殿明 | Process for preparing leukemia medicines |
| CN1274599A (en) * | 1999-05-20 | 2000-11-29 | 周金龙 | Cancer treating medicine and its preparation |
| CN101953975A (en) * | 2010-09-30 | 2011-01-26 | 倪海清 | Oral Chinese medicinal herbal tablets for treating tumors and preparation method |
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| CN1260983C (en) * | 2003-06-24 | 2006-06-21 | 中兴通讯股份有限公司 | A method of disaster recovery for home location register (HLR) with zero-time service take-over |
| CN1274599C (en) * | 2004-04-23 | 2006-09-13 | 中国科学院过程工程研究所 | Production method of calcium carbonate with high ratio surface area |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260983A (en) * | 1999-01-21 | 2000-07-26 | 仇殿明 | Process for preparing leukemia medicines |
| CN1274599A (en) * | 1999-05-20 | 2000-11-29 | 周金龙 | Cancer treating medicine and its preparation |
| CN101953975A (en) * | 2010-09-30 | 2011-01-26 | 倪海清 | Oral Chinese medicinal herbal tablets for treating tumors and preparation method |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104381541A (en) * | 2014-11-27 | 2015-03-04 | 常熟市海虞茶叶有限公司 | Anticancer tea |
| CN106138726A (en) * | 2016-07-29 | 2016-11-23 | 广州加原医药科技有限公司 | A kind of Chinese medicine composition of reverse multiple drug resistance of tumor |
| CN106309545A (en) * | 2016-08-01 | 2017-01-11 | 广州加原医药科技有限公司 | Chinese medicinal composition for reversing tumor multidrug resistance (MDR) and preparation method thereof |
| CN108186923A (en) * | 2018-02-02 | 2018-06-22 | 广州国宇医药科技有限公司 | A kind of Chinese medicine oat seaweed sugar composite and preparation method thereof |
| CN112138066A (en) * | 2020-09-09 | 2020-12-29 | 中南大学湘雅医院 | Application of black nightshade or black nightshade extract in increasing antibiotic or antineoplastic drug sensitivity |
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