CN104000965A - Lung-cancer-resistant composition and application thereof - Google Patents
Lung-cancer-resistant composition and application thereof Download PDFInfo
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- CN104000965A CN104000965A CN201410239263.8A CN201410239263A CN104000965A CN 104000965 A CN104000965 A CN 104000965A CN 201410239263 A CN201410239263 A CN 201410239263A CN 104000965 A CN104000965 A CN 104000965A
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Abstract
The invention belongs to the technical field of pharmaceuticals and particularly relates to a lung-cancer-resistant composition and an application thereof. The lung-cancer-resistant composition disclosed by the invention is characterized by comprising 160-200 parts of ginseng, 50-90 parts of radix adenophorae and 60-120 parts of oldenlandia diffusa. The invention also provides the application of the composition to preparation of lung-cancer-resistant drugs. The lung-cancer-resistant composition has the beneficial effects that experiments prove that the drugs respectively have an efficient anti-cancer effect; and 2, the anti-cancer mechanism of the drugs is possible as follows: the transportation function of an L-amino acid transporter 1 is inhibited by effective ingredients in the drugs, so that a favorable anti-cancer effect is achieved.
Description
Technical field
The invention belongs to pharmaceutical technology field.Particularly, the present invention relates to a kind of anti-pulmonary carcinoma compositions and application thereof.
Background technology
In recent years, lung cancer morbidity rate and mortality rate increase the fastest, and population health and life are threatened to one of maximum malignant tumor.Over nearly 50 years, many countries all report that the M & M of pulmonary carcinoma all obviously increases, and male lung cancer M & M all accounts for first of all malignant tumor, and women's sickness rate accounts for second, and mortality rate accounts for second.The cause of disease of pulmonary carcinoma is still not exclusively clear and definite so far, and great mass of data shows, long-term a large amount of smoking and pulmonary carcinoma have a very close relationship.
The treatment means of pulmonary carcinoma has operation, radiotherapy, Drug therapy at present, and the Comprehensive Treatment of above-mentioned therapy.In Drug therapy, Chinese medicine, because lasting medicine, side effect are little, becomes patient's first-selection, take to alleviate patient's misery, extend its life, improve its quality of life as object, and on market, this type of Chinese medicine is many, but ubiquity uncertain therapeutic efficacy cuts, the problem that effective percentage is low.
L-type amino acid transport body 1(L-type amino acid transporter 1, LAT1) be that in recent years find a kind of (comprises renal carcinoma at cancerous cell, carcinoma of prostate, bladder cancer, colorectal cancer, gastric cancer, breast carcinoma, cancer of pancreas, pulmonary carcinoma etc.) the medicine transmembrane transporter matter of surface specific high expressed.Studies show that, LAT1 function is mainly in cancerous cell, to transport the needed essential amino acids of protein synthesis, for the Hypersegmentation of cancerous cell, breeds " nutrition supply " that provides sufficient, and the fast breeding of cancerous cell is played an important role.Therefore, if certain medicine can suppress the expression of LAT1, just can treat to a certain extent the growth of anticancer, this medicine has the prospect that becomes cancer therapy drug.
In the process of medicine of screening treatment cervical cancer, saponins material, because plant origin is abundant, easily obtains, good effect, and untoward reaction is lower, is once becoming the target that people pay close attention to.Radix Ginseng is the dry root of Araliaceae Panax herbaceous plant Radix Ginseng, and the main component of Radix Ginseng is ginsenoside, and ginsenoside monomer compound has antitumor, resisting fatigue, the anti-ageing effect of waiting for a long time.Ginsenoside Rb1 and Rg1 content in natural plants is higher, and Rg3, Rh2, compand K equal size are less.Many pharmacological researches show, rare ginsenoside (as Rh1, Rh2, Rg3, Rb3 etc.) drug effect is more precious, at some refractory disease, aspect oncotherapy, show unique curative effect, therefore, Radix Ginseng is carried out to processed, increase the content of the rare saponin of Radix Ginseng, while screening of medicaments prescription compatibility, forming an effective anticancer prescription is the key that those skilled in the art study.
Summary of the invention
For solving the problems of the technologies described above, the invention provides a kind of anti-pulmonary carcinoma compositions and application thereof.
A kind of anti-pulmonary carcinoma compositions of the present invention, is characterized in that, by Radix Ginseng, and Rhizoma Curculiginis, Shi Jianchuan, Pericarpium Trichosanthis, Herba Epimedii forms, and wherein, described Radix Ginseng is 160-200 part, Rhizoma Curculiginis is 15-30 part, and Shi Jianchuan is 30-80 part, and Pericarpium Trichosanthis is 60-100 part, Herba Epimedii 80-120 part.
Further, Radix Ginseng is 180-195 part, and Rhizoma Curculiginis is 18-28 part, and Shi Jianchuan is 48-75 part, and Pericarpium Trichosanthis is 80-90 part, Herba Epimedii 85-110 part.
Further, described Radix Ginseng is processed through following method: ginseng raw material is pulverized to 20-40 order, use the water of ginseng raw material 50%-70% weight moistening, spray into the Rhizopus oryzae bacterium liquid of ginseng raw material 5-20% weight, aerobic fermentation 24-72 hour under 25-30 ℃ of condition, obtains biologic converted ginseng.
Further, described Radix Ginseng is any one or several in fresh ginseng, dry ginseng, Radix Ginseng Rubra.
Further, a kind of anti-pulmonary carcinoma compositions and pharmaceutically acceptable carrier form.
In said pharmacy, the complementary composition of acceptable, can comprise the filler that can accept and use such as in the solid preparation form oral drug preparations such as the slow release formulation at tablet, pill, granule, capsule or appropriate format: as starch, dextrin, Icing Sugar, pregelatinized Starch, lactose, glucose, calcium carbonate etc.; Adhesive: as hypromellose, polyvidone, starch slurry, dextrin slurry, syrup, rubber cement, arabic gum etc.; Excipient, lubricant: as magnesium stearate, sodium stearate, Pulvis Talci, micropowder silica gel, liquid paraffin, Polyethylene Glycol etc.; Substrate in soft capsule: as vegetable oil, Polyethylene Glycol etc.; Antioxidant: as sodium sulfite, ascorbic acid, cysteine, vitamin E etc.; Blocker in oral sustained-release preparation: as Cera Flava, Brazil wax, hydrogenated vegetable oil, stearic acid, polyvidone, ethyl cellulose etc.; In ejection preparation, allow solvent, cosolvent, stabilizing agent and the additives etc. that use.Through corresponding formulation method and process, can prepare the medicine of corresponding oral or ejection preparation form.The substrate of using in suppository: as cocoa butter, semi-synthetic glycerine fatty acid esters, Oleum Linderae, hydrogenation wet goods; Water solublity and hydrophilic matrix: as glycerin gelatine, Polyethylene Glycol, tween-61, polyoxyethylene stearate (40) ester, water-soluble chitosan, poloxamer etc.; Absorb blocker: as soybean lecithin, alginic acid, hydroxypropyl first class cellulose, stearic acid, Cera Flava etc.; In ointment, use pharmaceutically acceptable auxiliaries or excipient, as adhesive: as pregelatinized Starch, hydroxypropyl cellulose etc., filler: as lactose, sucrose, mannitol etc.; Lubricant: as stearic acid, Polyethylene Glycol, magnesium stearate, Pulvis Talci, silicon dioxide etc., disintegrating agent: as starch, sodium carboxymethyl cellulose; Lubricant: as sodium lauryl sulphate etc.
Wherein, oral formulations is preferably tablet, capsule, pill, granule, drop pill, soft capsule, suspension, solution, syrup, nano-emulsion, liposome; The preferred freeze-dried powder of ejection preparation, vein emulsion, liposome, nano-emulsion; The preferred suppository of external preparation, ointment.
The present invention also provides the application of above-mentioned composition in preparing anti-lung-cancer medicament.
Wherein, anti-lung-cancer medicament is preferably the compositions that contains Radix Ginseng for pulmonary carcinoma.
Process for preparing medicine of the present invention is: aforesaid raw material is mixed by corresponding weight proportion, first with clear water, clean remove impurity, the warm water soaking 1-3h of 30-50 ℃ of quality such as then used, then, add raw material weight 3-5 water doubly, at 75-90 ℃, extract 3-5 time, after cold filtration, at 65 ℃ of following concentrated flowing soaking pastes that become with the quality such as raw material, shake up sealing, as for shady and cool ventilation place, preserve.Above-mentioned extractum can directly be done medicinal, also can be used for model test as anticancer in animal.
Beneficial effect of the present invention is: 1, checking by experiment, compositions has efficient anticancer effect.2, the anticancer mechanism of compositions is likely the transport function that has suppressed L-type amino acid transport body 1 due to the effective ingredient in medicine, thereby reaches good anticancer effect.
Accompanying drawing explanation
Fig. 1 is the suppression ratio of the anti-pulmonary carcinoma compositions of variable concentrations to lung carcinoma cell H1975 growth in vitro.
The specific embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, the embodiment providing is only in order to illustrate the present invention, rather than in order to limit the scope of the invention.
Experimental technique in following embodiment, if no special instructions, is conventional method; Test material used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop; Rhizopus oryzae in following embodiment (rhizopus Rhizopus oryzae) is purchased from Chinese common micro-organisms culture presevation administrative center, bacterial strain deposit number: cgmcc3.6919, original number: 3.851.
embodiment 1:
Chinese medicine composition by following raw material is by weight ratio: Radix Ginseng is 200 grams, and Rhizoma Curculiginis is 30 grams, and Shi Jianchuan is 30 grams, and Pericarpium Trichosanthis is 60 grams, 80 grams of Herba Epimedii.
Ginseng raw material is pulverized 20-40 order, and wherein, described Radix Ginseng is fresh ginseng, moistening with the water of ginseng raw material's 50% weight, sprays into the Rhizopus oryzae bacterium liquid of ginseng raw material's 5% weight, and under 25-30 ℃ of condition, aerobic fermentation is 24 hours, obtains biologic converted ginseng.
Preparation method is: first with clear water, clean remove impurity, the warm water soaking 1h of 50 ℃ of quality such as then used, then, the water that adds 5 times of raw material weights, extracts 3 times at 75 ℃, after cold filtration, at 65 ℃ of following concentrated flowing soaking pastes that become with the quality such as raw material, obtain No. 1, anti-pulmonary carcinoma compositions.
embodiment 2:
Chinese medicine composition by following raw material is by weight ratio: Radix Ginseng is 160 grams, and Rhizoma Curculiginis is 15 grams, and Shi Jianchuan is 80 grams, and Pericarpium Trichosanthis is 100 grams, 120 grams of Herba Epimedii.
Ginseng raw material is pulverized 20-40 order, and Radix Ginseng is dry ginseng and Radix Ginseng Rubra mixture, and weight ratio is 1:1, moistening with the water of ginseng raw material's 70% weight, the Rhizopus oryzae bacterium liquid that sprays into ginseng raw material's 20% weight, under 25-30 ℃ of condition, aerobic fermentation is 72 hours, obtains biologic converted ginseng.
Preparation method is: aforesaid raw material is mixed by corresponding weight proportion, first with clear water, clean remove impurity, the warm water soaking 3h of 30 ℃ of quality such as then used, then, the water that adds 3 times of raw material weights, extracts 5 times at 80 ℃, after cold filtration, at 65 ℃ of following concentrated flowing soaking pastes that become with the quality such as raw material, obtain No. 2, anti-pulmonary carcinoma compositions.
embodiment 3:
Chinese medicine composition by following raw material is by weight ratio: Radix Ginseng is 195 grams, and Rhizoma Curculiginis is 28 grams, and Shi Jianchuan is 48 grams, and Pericarpium Trichosanthis is 80 grams, 85 grams of Herba Epimedii.
Ginseng raw material is pulverized 20-40 order, and described Radix Ginseng is Radix Ginseng Rubra, moistening with the water of ginseng raw material's 67% weight, sprays into the Rhizopus oryzae bacterium liquid of ginseng raw material's 17% weight, and under 25-30 ℃ of condition, aerobic fermentation is 38 hours, obtains biologic converted ginseng.
Preparation method is: first with clear water, clean remove impurity, the warm water soaking 2.5h of 44 ℃ of quality such as then used, then, the water that adds 4 times of raw material weights, at 90 ℃, extract 4 times, after cold filtration, at 65 ℃ of following concentrated flowing soaking pastes that become with the quality such as raw material, shake up sealing, obtain No. 3, anti-pulmonary carcinoma compositions.
embodiment 4:
In the present embodiment, proved that by experiment anti-pulmonary carcinoma compositions has good effect aspect treatment pulmonary carcinoma No. 3.
1. materials and methods
1.1 tested medicines
No. 3, anti-pulmonary carcinoma compositions
1.2 cell strains:
Non-small cell lung cancer cell H1975.
1.3 main agents
DMEM, RPMI1640, F12K, McCoy ' s 5A culture medium step (Beijing) Science and Technology Ltd. in morning purchased from He Zhong section of Hycelone company, hyclone (FBS), pancreatin are purchased from Gibco company, PBS powder is purchased from Sigma company, 100X mycillin solution is purchased from Beijing Suo Laibao Science and Technology Ltd., MTS one-step method cell viability detection kit (Promega).
1.4 instrument
Zenyth 1100 multifunction scanners: Austrian Anthos company produces; IC 1000 Countstar full-automatic cell calculating instruments: Rui Yu bio tech ltd, Shanghai; HFsafe Biohazard Safety Equipment: the holding company limited of power health biologic medical science and technology; HERAcell 150i CO
2incubator: Thermo Scientific company; LD5-2A low speed centrifuge: Beijing Medical Centrifugal Machine Factory.
1.5 experimental technique
1.5.1 the In vitro culture of human cancer cell and bed board
Above-mentioned people source cancerous cell is cultivated based on 37 ℃, 5%CO with DMEM/RPMI1640/F12K/McCoy ' the S 5A containing 10%FBS and mycillin
2, 95% saturated humidity incubator in cellar culture, go down to posterity, treat that Growth of Cells, to merging, with pancreatin, attached cell being digested in super-clean bench, becomes 10 with culture medium suspendible
4~ 10
5the cell suspension of cells/ml, is laid on 96 orifice plates, and every hole paving cell suspension 100 μ l, continue to cultivate 24 h.
1.5.2 medicine preparation and 96 orifice plate dispensings
1.5.2.1 No. 3, anti-pulmonary carcinoma compositions
Precision takes No. 3 600mg of anti-pulmonary carcinoma compositions, DPBS with 10ml dissolves rear centrifugal 12000rpm 40min, get supernatant and after the microporous filter membrane aseptic filtration of 0.22 μ m, with culture medium stepwise dilution, become again that stepwise dilution becomes 30,15,7.5,3.75,1.875,0.94, the solution of 0.47mg/ml, throw in 96 orifice plates, every hole 50 μ l, make final concentration in hole be respectively 10,5,2.5,1.25,0.63,0.31 and 0.15mg/kg, the culture medium of control wells administration same volume, continues to cultivate 48 h.
1.5.3 MTT measures
Offer medicine after 48 h the reagent in MTS one-step method cell viability detection kit, every hole adds 20 μ l, puts into CO
2in incubator, continue to cultivate 1 ~ 3h, application fluorescent scanning instrument is measured the OD value in every hole at 492nm place, and the color of the solubility first a ceremonial jade-ladle, used in libation that the survivaling cell in every hole is produced is measured.
1.5.4 result is calculated
According to the OD value in every hole, by following formula, calculate the suppression ratio of cell growth:
Suppression ratio (%)=(the average OD value of the average OD value-administration of matched group group) average OD value * 100% of/matched group
2. result
The growth in vitro inhibitory action of 2.1 No. 3, anti-pulmonary carcinoma compositionss to cancerous cell
Result of the test is visible, and non-small cell lung cancer cell H1975 is subject to inhibition in various degree in growth course in vitro, about 43.37%(± 15.83 of suppression ratio) more than.The inhibition concentration that No. 3, anti-pulmonary carcinoma compositions is 0.15 ~ 10mg/ml, visible 3 the more than concentration dose-dependences (in Table 1) of H1975.
3. conclusion
The growth in vitro of No. 3 Dui Ren source cancerous cell lines of anti-pulmonary carcinoma compositions has certain inhibitory action.
No. 3, the anti-pulmonary carcinoma compositions of the table 1 growth in vitro inhibitory action to lung carcinoma cell
embodiment 5:
In the present embodiment, proved that by experiment compositions has good effect aspect anti-pulmonary carcinoma.
1. test material
1.1 medicine
No. 3, anti-pulmonary carcinoma compositions: give nude mice oral administration gavage after being made into suspension with 0.5% sodium carboxymethyl cellulose (CMC) during test;
Positive control drug: Cyclophosphamide for injection, 0.2g/ props up, and lot number 04130205, is produced by Shanxi Powerdone Pharmaceutical Co., Ltd..During test, to give nude mice abdominal cavity after physiological saline solution, inject (i.p.).
1.2 cell strain
Non-small cell lung carcinoma NCI-H1975 cell, buys the cell bank in the Chinese Academy of Sciences.
1.3 animal
ALB/c-nu nude mouse, ♂, SPF level, 18 ~ 20g, buys in Beijing Vital River Experimental Animals Technology Co., Ltd., credit number SCXK(capital) 2012-0001, the animal quality quality certification numbers 11400700039362.
2. test method
By NCI-H1975 cell recovery, carry out cellar culture, adherent growth collecting cell suspension after 2 generations, and be diluted to 10 with culture medium
7the concentration of individual/ml, respectively subcutaneous injection, in nude mice bilateral oxter, is taken tumor after tumor grows up to, and is cut into the fritter of 2 * 2mm size under gnotobasis, transplants in the one-sided axillary fossa of nude mice subcutaneously, after according to said method going down to posterity, starts administration.
Before administration, according to gross tumor volume, NCI-H1975 tumor bearing nude mice is respectively divided into 5 groups, comprises model control group, positive drug control group, No. 3 high, medium and low three dosage groups of anti-pulmonary carcinoma compositions, 5 every group.Treat the 3rd tumor growth to 100 mm that goes down to posterity in body
3rear beginning oral administration, positive drug control group i.p. cyclophosphamide 50mg/kg, once, No. 3, anti-pulmonary carcinoma compositions is by 100,300 and the oral administration gavage administration respectively of 900mg crude drug/kg dosage in injection in every two weeks, once a day, continuous 30 days.After administration 30 days, get tumor piece, thymus and spleen, weigh and calculate tumour inhibiting rate, thymus index and index and spleen index, formula is as follows: tumour inhibiting rate=(heavy/blank group tumor of blank group tumor weight-administration group tumor weight) * 100%; Thymus index=thymus weight/body weight (mg/g); Mean in number=spleen/body weight (mg/g) of spleen.
3. result of the test
The antitumor action of 3.1 pairs of NCI-H1975 heterotopic transplantation tumor nude mices
Experimental result demonstration, compares with blank group, and anti-pulmonary carcinoma compositions shows good inhibitory action to lung carcinoma cell NCI-H1975 heterotopic transplantation tumor No. 3, and tumour inhibiting rate reaches as high as 44.87%, and tumor heavily has utmost point significant difference (P<0.01).Anti-pulmonary carcinoma compositions does not have inhibitory action (table 2) to the increase of the body weight of mice No. 3 in performance antitumor action.
4. conclusion
(1) anti-pulmonary carcinoma compositions has good inhibitory action to the growth of NCI-H1975 tumor-bearing mice tumor No. 3;
(2) anti-pulmonary carcinoma compositions No. 3 100,300,900mg crude drug/kg dosage are to the body weight gain of NCI-H1975 people's pulmonary carcinoma transplanted tumor nude mice and model group no significant difference relatively.
No. 3, the anti-pulmonary carcinoma compositions of table 2. inhibitory action (n=10) to lung carcinoma cell NCI-H1975 heterotopic transplantation tumor
Claims (8)
1. an anti-pulmonary carcinoma compositions, is characterized in that, by Radix Ginseng, and Rhizoma Curculiginis, Shi Jianchuan, Pericarpium Trichosanthis, Herba Epimedii forms, and wherein, described Radix Ginseng is 160-200 part, and Rhizoma Curculiginis is 15-30 part, and Shi Jianchuan is 30-80 part, Pericarpium Trichosanthis is 60-100 part, Herba Epimedii 80-120 part.
2. a kind of anti-pulmonary carcinoma compositions according to claim 1, is characterized in that, described Radix Ginseng is 180-195 part, and Rhizoma Curculiginis is 18-28 part, and Shi Jianchuan is 48-75 part, and Pericarpium Trichosanthis is 80-90 part, Herba Epimedii 85-110 part.
3. a kind of anti-pulmonary carcinoma compositions according to claim 2, it is characterized in that, described Radix Ginseng is processed through following method: ginseng raw material is pulverized to 20-40 order, moistening with the water of ginseng raw material 50%-70% weight, spray into the Rhizopus oryzae bacterium liquid of ginseng raw material 5-20% weight, aerobic fermentation 24-72 hour under 25-30 ℃ of condition, obtains biologic converted ginseng.
4. according to a kind of anti-pulmonary carcinoma compositions described in claim 1-3 any one, it is characterized in that, described Radix Ginseng is any one or several in fresh ginseng, dry ginseng, Radix Ginseng Rubra.
5. according to a kind of anti-pulmonary carcinoma compositions described in claim 1-3 any one, it is characterized in that forming with pharmaceutically acceptable carrier.
6. according to a kind of anti-pulmonary carcinoma compositions described in claim 1-3 any one, it is characterized in that, oral formulations can be tablet, capsule, pill, granule, drop pill, soft capsule, suspension, solution, syrup, nano-emulsion, liposome.
7. according to a kind of anti-pulmonary carcinoma compositions described in claim 1-3 any one, it is characterized in that injection preparation can be freeze-dried powder, injection vein emulsion, injection, liposome, nano-emulsion, transfusion; External preparation can be suppository, ointment.
8. anti-pulmonary carcinoma compositions as claimed in claim 1 application in treatment anti-lung-cancer medicament as effective ingredient.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105213530A (en) * | 2015-11-03 | 2016-01-06 | 王朋 | A kind of Ampelopteris prolifera (Retz.) Copel. and Radix rubi buergeri composite extract and its preparation method and application |
-
2014
- 2014-05-30 CN CN201410239263.8A patent/CN104000965A/en active Pending
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Application publication date: 20140827 |