CN105194126A - Application of croton tiglium alkaloid in preparation of medicine for treating lung cancer - Google Patents
Application of croton tiglium alkaloid in preparation of medicine for treating lung cancer Download PDFInfo
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Abstract
The invention discloses application of croton tiglium alkaloid in preparation of medicine for treating lung cancer, and belongs to the technical field of medicine. The medicine is prepared from, by weight, 5-10 parts of croton tiglium alkaloid, 1-2 parts of naringin, 2-4 parts of scutellaria baicalensis alkaloid, 0.5-2 parts of purple quercetin, 1-2 parts of liriodendron tulipifera alkaloid, 2-5 parts of coptidis rhizoma alkaloid, 1-3 parts of tacca plantaginea saponin and 2-6 parts of radix glycyrrhizae alkaloid. Croton tiglium alkaloid in the medicine restrains growth of lung adenocarcinoma cells A549 and promotes lung adenocarcinoma cells A549 to die through a Bax/Bcl-2 approach, medicine effects of all the raw materials of dropping pills supplement one another and bring out the best in one another, and the medicine has remarkable effects on restraining growth of lung cancer cells and promoting lung cancer cells to die under the mutual concurrent effects of all the raw materials, has an effect on treating lung cancer, is remarkable in curative effect, relieves pains of patients, prolongs lifetime, improves life quality, and provides a new direction for treatment of clinical lung cancer.
Description
Technical field
The invention belongs to the technical field of medicine, refer to the application of a kind of croton seed alkaloid in the medicine of preparation treatment pulmonary carcinoma especially.
Background technology
Pulmonary carcinoma becomes one of the highest malignant tumor of global incidence rate already, and wherein 85% is nonsmall-cell lung cancer (non-smallcelllungcancer, NSCLC).In China, the M & M of pulmonary carcinoma rises rapidly in recent years.The means of current treatment pulmonary carcinoma are still operation, chemotherapy, radiotherapy, targeted therapy and biological immune Supporting Therapy.Large quantity research both domestic and external shows: pulmonary carcinoma is a kind of malignant tumor that organs shifts that very easily occurs, mostly is middle and advanced stage, loses opportunity of operation during discovery, and chemotherapy mostly is first-selected.
In recent years, for the medicine of chemotherapy without major progress, and expensive, how to develop new medicine, improve curative effect, reduce side effect one of focus becoming current research.In Drug therapy, Chinese medicine is little because of lasting medicine, side effect, becomes the first-selection of patient, and to alleviate patient's misery, extend its life, to improve for the purpose of its quality of life, on market, this type of Chinese medicine is many, but ubiquity uncertain therapeutic efficacy is cut, the problem that effective percentage is low.
Summary of the invention
The invention provides the application of a kind of croton seed alkaloid in the medicine of preparation treatment pulmonary carcinoma, solve in prior art the problem that the medicine for the treatment of pulmonary carcinoma takes effect slowly, weak curative effect, effective percentage are low.
For solving the problems of the technologies described above, the technical solution used in the present invention is: the application of croton seed alkaloid in the medicine of preparation treatment pulmonary carcinoma, described medicine comprises the raw material of following weight portion: croton seed alkaloid 5-10 part, naringin 1-2 part, Radix Scutellariae alkaloid 2-4 part, rutin 0.5-2 part, Liriodendron alkaloid 1-2 part, Rhizoma Coptidis alkaloid 2-5 part, dehiscent fruit potato saponin 1-3 part, Radix Glycyrrhizae alkaloid 2-6 part.
As the preferred embodiment of one, described medicine comprises the raw material of following weight portion: croton seed alkaloid 8 parts, naringin 1.5 parts, Radix Scutellariae alkaloid 3 parts, rutin 1.5 parts, Liriodendron alkaloid 1.5 parts, Rhizoma Coptidis alkaloid 3 parts, dehiscent fruit potato saponin 2 parts, Radix Glycyrrhizae alkaloid 4.5 parts.
As the preferred embodiment of one, the dosage form of described medicine is drop pill type.
As the preferred embodiment of one, described drop pill type medicine also comprises PEG 8000 60-100 weight portion.
A kind of preparation method for the treatment of the croton seed alkaloid medicine of pulmonary carcinoma of the present invention, it mainly realizes by the following technical programs so in addition: comprise the following steps: 1) taking polyethylene glycol 8000, be heated to melting, stir, make substrate; 2) get croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid, grinding, screening, obtains mixed-powder; 3) by step 2) gained mixed-powder adds step 2) in gained substrate, fully stir, make uniform medicinal liquid; 4) step 3) gained medicinal liquid is instilled in the dimethicone of 2-4 DEG C under the heat-retaining condition of 85-95 DEG C, take out after drop pill molding, wipe the dimethicone on drop pill surface with absorbent paper, naturally dry, to obtain final product.
As the preferred embodiment of one, in described step 4), drip speed and drip/min for 30-60, dripping a distance is 2.0-4.0cm.
As the preferred embodiment of one, in described step 1), PEG 8000 adopts the heating in water bath of 85-95 DEG C.
Usage and consumption: drop pill of the present invention, every ball specification is 50mg, one after each meal, and every day takes night and morning, and each 3-4 grain, warm water takes.
Beneficial effect of the present invention: the present invention utilizes the pure mixing under the effect of PEG 8000 of croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid and makes the drop pill medicine for the treatment of pulmonary carcinoma, the medicinal liquid state of this drop pill is moderate, roundness is moderate, smooth surface, hardness is moderate, and content of dispersion is more, its water solublity, dispersibility and good stability, taking convenience, can use throughout the year; The present invention utilizes croton seed alkaloid suppress the growth of Lung Adenocarcinoma A 549 Cell by Bax/Bcl-2 approach and promote its apoptosis, croton seed alkaloid and other raw material are worked in coordination with mutually, drug effect complements each other, bring out the best in each other, through focus depths, nurse one's health patient body inside function, gained drop pill has the effect significantly suppressing lung cancer cell growth and promote its apoptosis, serves the effect for the treatment of pulmonary carcinoma comprehensively; Its good effect, instant effect, dose is few, mild in medicine property and, gentle easily clothes, secondary injury can not be caused to patient body, effectively can alleviate cough, uncomfortable in chest, the symptom of puzzlement lung cancer patient such as to feel suffocated, the quality of life of patient can be significantly improved, extend the existence time limit, for clinical treatment pulmonary carcinoma provides a kind of new direction.
Accompanying drawing explanation
Fig. 1 is the morphology picture of the croton seed alkaloid intervention A549 cell of variable concentrations under inverted phase contrast microscope;
Fig. 2 is the expression of results figure that cellular immunofluorescence method detects Bax;
Fig. 3 is the expression of results figure that cellular immunofluorescence method detects Bcl-2;
In figure: A-matched group, namely the concentration of croton seed alkaloid is 0 μ g/ml; B-concentration is the croton seed alkaloid experimental group of 10 μ g/ml; C-concentration is the croton seed alkaloid experimental group of 50 μ g/ml; D-concentration is the croton seed alkaloid experimental group of 100 μ g/ml; E-concentration is the croton seed alkaloid experimental group of 200 μ g/ml.
Detailed description of the invention
Be clearly and completely described technical scheme of the present invention below in conjunction with specific embodiments of the invention, obviously, described embodiment is only a part of embodiment of the present invention, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
The application of a kind of croton seed alkaloid of the present invention in the medicine of preparation treatment pulmonary carcinoma, described medicine comprises the raw material of following weight portion: croton seed alkaloid 5-10 part, naringin 1-2 part, Radix Scutellariae alkaloid 2-4 part, rutin 0.5-2 part, Liriodendron alkaloid 1-2 part, Rhizoma Coptidis alkaloid 2-5 part, dehiscent fruit potato saponin 1-3 part, Radix Glycyrrhizae alkaloid 2-6 part.
Preferably, described medicine comprises the raw material of following weight portion: croton seed alkaloid 8 parts, naringin 1.5 parts, Radix Scutellariae alkaloid 3 parts, rutin 1.5 parts, Liriodendron alkaloid 1.5 parts, Rhizoma Coptidis alkaloid 3 parts, dehiscent fruit potato saponin 2 parts, Radix Glycyrrhizae alkaloid 4.5 parts
Further, the dosage form of described medicine is drop pill type.
Particularly, described drop pill type medicine also comprises PEG 8000 60-100 weight portion.
A kind of preparation method for the treatment of the croton seed alkaloid medicine of pulmonary carcinoma of the present invention, comprises the following steps: 1) taking polyethylene glycol 8000, is heated to melting, stirs, make substrate; 2) get croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid, grinding, screening, obtains mixed-powder; 3) by step 2) gained mixed-powder adds step 2) in gained substrate, fully stir, make uniform medicinal liquid; 4) step 3) gained medicinal liquid is instilled in the dimethicone of 2-4 DEG C under the heat-retaining condition of 85-95 DEG C, take out after drop pill molding, wipe the dimethicone on drop pill surface with absorbent paper, naturally dry, to obtain final product.
Preferably, in described step 4), drip speed and drip/min for 30-60, dripping a distance is 2.0-4.0cm.
Further, in described step 1), PEG 8000 adopts the heating in water bath of 85-95 DEG C.
embodiment one
Treat a preparation method for the croton seed alkaloid medicine of pulmonary carcinoma, comprise the following steps: the PEG 8000 getting 60 weight portions, is heated to melting, stirs, and makes substrate; The Radix Glycyrrhizae alkaloid of the Liriodendron alkaloid of the Radix Scutellariae alkaloid of the croton seed alkaloid of 5 weight portions, the naringin of 1 weight portion, 2 weight portions, the rutin of 0.5 weight portion, 1 weight portion, the Rhizoma Coptidis alkaloid of 2 weight portions, the dehiscent fruit potato saponin of 1 weight portion and 2 weight portions, grinding, screening, obtains mixed-powder; Mixed-powder is added in above-mentioned substrate, fully stirs, make uniform medicinal liquid; Above-mentioned medicinal liquid is instilled in the dimethicone of 2 DEG C under the heat-retaining condition of 85 DEG C, takes out after drop pill molding, wipe the dimethicone on drop pill surface with absorbent paper, naturally dry, to obtain final product.
Wherein, croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid are the existing product directly purchased, and also can be the products conventionally extracting from its correspondingly raw material and obtain.
embodiment two
Treat a preparation method for the croton seed alkaloid medicine of pulmonary carcinoma, comprise the following steps: the PEG 8000 getting 70 weight portions, adopt the heating in water bath of 85 DEG C to melting, stir, make substrate; The Radix Glycyrrhizae alkaloid of the Liriodendron alkaloid of the Radix Scutellariae alkaloid of the croton seed alkaloid of 6 weight portions, the naringin of 1.5 weight portions, 3 weight portions, the rutin of 1 weight portion, 1.5 weight portions, the Rhizoma Coptidis alkaloid of 3 weight portions, the dehiscent fruit potato saponin of 1.5 weight portions and 3 weight portions, grinding, screening, obtains mixed-powder; Mixed-powder is added in above-mentioned substrate, fully stirs, make uniform medicinal liquid; Instilled under the heat-retaining condition of 85 DEG C in the dimethicone of 3 DEG C by above-mentioned medicinal liquid, wherein, dripping speed is 30/min, dripping apart from being 2.0cm, taking out, wipe the dimethicone on drop pill surface, naturally dry, to obtain final product with absorbent paper after drop pill molding.
Wherein, croton seed alkaloid, Radix Scutellariae alkaloid, Rhizoma Coptidis alkaloid and Radix Glycyrrhizae alkaloid are respectively and conventionally extract dry obtaining from Fructus Crotonis, Radix Scutellariae, Rhizoma Coptidis and Radix Glycyrrhizaes; Naringin, rutin, Liriodendron alkaloid and dehiscent fruit potato saponin are the existing product directly purchased.
embodiment three
Treat a preparation method for the croton seed alkaloid medicine of pulmonary carcinoma, comprise the following steps: the PEG 8000 getting 80 weight portions, adopt the heating in water bath of 90 DEG C to melting, stir, make substrate; The Radix Glycyrrhizae alkaloid of the Liriodendron alkaloid of the Radix Scutellariae alkaloid of the croton seed alkaloid of 7 weight portions, the naringin of 2 weight portions, 4 weight portions, the rutin of 1.5 weight portions, 2 weight portions, the Rhizoma Coptidis alkaloid of 4 weight portions, the dehiscent fruit potato saponin of 2 weight portions and 4 weight portions, grinding, screening, obtains mixed-powder; Mixed-powder is added in above-mentioned substrate, fully stirs, make uniform medicinal liquid; Instilled under the heat-retaining condition of 90 DEG C in the dimethicone of 4 DEG C by above-mentioned medicinal liquid, wherein, dripping speed is 60/min, dripping apart from being 4.0cm, taking out, wipe the dimethicone on drop pill surface, naturally dry, to obtain final product with absorbent paper after drop pill molding.
Wherein, croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid are respectively and conventionally extract dry obtaining from Fructus Crotonis, pomelo peel, Radix Scutellariae, Flos Sophorae, Liriodendron, Rhizoma Coptidis, dehiscent fruit potato and Radix Glycyrrhizaes.
embodiment four
Treat a preparation method for the croton seed alkaloid medicine of pulmonary carcinoma, comprise the following steps: the PEG 8000 getting 90 weight portions, adopt the heating in water bath of 95 DEG C to melting, stir, make substrate; The Radix Glycyrrhizae alkaloid of the Liriodendron alkaloid of the Radix Scutellariae alkaloid of the croton seed alkaloid of 10 weight portions, the naringin of 2 weight portions, 4 weight portions, the rutin of 2 weight portions, 2 weight portions, the Rhizoma Coptidis alkaloid of 5 weight portions, the dehiscent fruit potato saponin of 3 weight portions and 6 weight portions, grinding, screening, obtains mixed-powder; Mixed-powder is added in above-mentioned substrate, fully stirs, make uniform medicinal liquid; Instilled under the heat-retaining condition of 95 DEG C in the dimethicone of 2 DEG C by above-mentioned medicinal liquid, wherein, dripping speed is 40/min, dripping apart from being 2.0cm, taking out, wipe the dimethicone on drop pill surface, naturally dry, to obtain final product with absorbent paper after drop pill molding.
embodiment five
Treat a preparation method for the croton seed alkaloid medicine of pulmonary carcinoma, comprise the following steps: the PEG 8000 getting 100 weight portions, adopt the heating in water bath of 90 DEG C to melting, stir, make substrate; The Radix Glycyrrhizae alkaloid of the Liriodendron alkaloid of the Radix Scutellariae alkaloid of the croton seed alkaloid of 8 weight portions, the naringin of 1.5 weight portions, 3 weight portions, the rutin of 1.5 weight portions, 1.5 weight portions, the Rhizoma Coptidis alkaloid of 3 weight portions, the dehiscent fruit potato saponin of 2 weight portions and 4.5 weight portions, grinding, screening, obtains mixed-powder; Mixed-powder is added in above-mentioned substrate, fully stirs, make uniform medicinal liquid; Instilled under the heat-retaining condition of 90 DEG C in the dimethicone of 3 DEG C by above-mentioned medicinal liquid, wherein, dripping speed is 50/min, dripping apart from being 3.0cm, taking out, wipe the dimethicone on drop pill surface, naturally dry, to obtain final product with absorbent paper after drop pill molding.
Wherein, croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid are the existing product directly purchased, and also can be the products conventionally extracting from its correspondingly raw material and obtain.
The present invention is set forth further below in conjunction with concrete test example.
Experimental example 1: measure croton seed alkaloid to the impact of external A549 cytoactive
Experiment material: DMEM culture fluid, hyclone, 0.25% trypsin, Hyclone company of the DMSO(U.S.).
Key instrument: cell culture incubator (U.S.), cryogenic refrigerator (China), centrifuge (France).
Cell strain and cell culture: lung adenocarcinoma cell line (A549 cell) takes from Zhongxin Hospital, Qingdao's tumor biotherapy center; 1 part of DMSO, 2 parts of hyclones, 7 parts containing the DMEM culture medium of 10% hyclone in frozen, recover and go down to posterity.
The A549 cell of exponential phase is in, with l × l0 with trypsinization
8/ L is evenly inoculated in 25cm
2in culture bottle, grow to after 80% fusion until cell, use serum-free medium instead and cultivate 24h, make Growth of Cells synchronously be still in the GO phase.Discard culture fluid, A549 cell is divided at random matched group and different croton seed alkaloid experimental group, matched group adds serum-free medium; The serum-free medium (the whole degree of croton seed alkaloid is respectively 10,50,100,200 μ g/m1) containing variable concentrations croton seed alkaloid that croton seed alkaloid experimental group adds equivalent respectively acts on 24-48h, and contains the serum-free medium effect 24h of croton seed alkaloid final concentration 100 μ g/mL; Collecting cell or culture fluid supernatant are tested.
Experimental result:
1, the cytoactive after mtt assay detection variable concentrations croton seed alkaloid intervention A549 cell
Table 1 lists croton seed alkaloid affects result to external A549 cytoactive, as can be seen from Table 1, the croton seed alkaloid of variable concentrations (0,10,50,100,200 μ g/ml) acted on external A549 cell after 24 hours, all had remarkable inhibitory action to the activity of cell.And along with the increase of drug level, cytoactive is suppressed to be increased gradually, shows as the dependence of dosage.Between experimental group, comparing difference all has statistical significance (P<0.05) between two.
Table 1 croton seed alkaloid on the impact of external A549 cytoactive (
)
Note: *---compare with matched group and have statistical significance (P<0.05); △---compare between group and have statistical significance (P<0.05).
2, external A549 morphological observation under inverted phase contrast microscope
Accompanying drawings 1, well, floating cells is less for Normal group and the external A549 cell growth state of A, and endochylema enriches, and karyon is high-visible, and in polygon, cell arrangement is tight, and iuntercellular is interconnected as seen; Be B after adopting 10ug/ml croton seed alkaloid to intervene external A549 cell 24h, most of attached cell has complete karyon and endochylema, the balling-up of fraction cell shrinkage.50ug/ml croton seed alkaloid is C after intervening A549 cell 24h, and see many floating cells, attached cell is rare complete karyon and endochylema, and most cells is gear shape, and the balling-up of part cell shrinkage.100ug/ml croton seed alkaloid is D after intervening A549 cell 24h, and see a large amount of floating cells, attached cell is almost without complete karyon and endochylema, and most cells shrinkage balling-up, without normal cell form.200ug/ml croton seed alkaloid is E after intervening A549 cell 24h, and compare with 100ug/ml group cellular morphology, situation is similar, visible a large amount of floating cells, attached cell, almost without complete karyon and endochylema, almost so cell shrinkage balling-up, loses normal cell form.
3, the apoptotic result of AnnexinV-PI staining examine
Table 2 croton seed alkaloid on the impact of A549 apoptosis rate (
)
Note: *---compare with matched group and have statistical significance (P<0.05).
As can be seen from Table 2, after variable concentrations croton seed alkaloid acts on external A549 cell, apoptosis rate compares with matched group, and when wherein concentration is 100 μ g/ml, apoptosis appears in cell; Compare with matched group, difference has statistical significance (P<0.05).
4, cellular immunofluorescence method detects Bax, Fas, Caspas-8, Bcl-2 protein expression result
Choosing concentration is that the croton seed alkaloid of 0 and 100 μ g/ml is tested, and each concentration establishes 5 multiple holes, and in triplicate, application cell immuno-fluorescence assay shows.Accompanying drawings 2, compares with matched group, and concentration is that the croton seed alkaloid experimental group pro apoptotic protein Bax of 100 μ g/ml expresses increase, and fluorescence intensity is high; Accompanying drawings 3, compares with matched group, and experimental group presses down apoptotic proteins Bcl-2 and expresses minimizing, and fluorescence intensity weakens; And the expression intensity of albumen Fas and Caspas-8 in matched group and experimental group is without obvious change.
5, RT-PCR method detects the expression that croton seed alkaloid acts on Bax, Fas, Caspas-8, Bcl-2mRNA after A549 cell
Adopt the method for RT-PCR have detected Bax, Fas, Caspas-8, Bcl-2mRNA different croton seed alkaloid concentration be 0 and 100ug/ml act on the expression of A549 cell.The expression of mRNA is with 2
-△ △ CTmethod representation.As can be seen from Table 3, be that 100 μ g/ml croton seed alkaloid experimental group BaxmRNA express increase in concentration, Bcl-2mRNA expresses minimizing, and its difference has statistical significance (P<0.05); The expression of Caspas-8mRNA in matched group and experimental group increases, but not statistically significant (P>0.05); And FasmRNA in matched group and experimental group without significant change, no significant difference (P>0.05).
The expression (n=9) of table 3Bax, Fas, Caspas-8, Bcl-2mRNA in matched group and different experiments group
note: *---compare with matched group and have statistical significance (P<0.05).
Experimental example 2: animal toxicity test
By the drop pill of the embodiment of the present invention one to embodiment five, carry out repeatedly animal toxicity test respectively; During each test, get rabbit 20, male and female dual-purpose, body weight 1.8-2.3kg, is divided into two groups, often organizes 10, wherein one group is overdose test group, another group is normal amount test group, and overdose test group consumption is 3.0g/kg, and normal amount test group consumption is 0.5g/kg, administering mode is administration by gavage administration, every day each 1 time sooner or later, take 10 days continuously, observe administration reaction every day; Test of many times all result shows, two groups of rabbit spirit, activity, diet, excretion are all normal; Cut open inspection, naked eyes examine main inside internal organs, no abnormality seen; Therefore, this drop pill is without bad toxic and side effects.
Experimental example 3: drop pill of the present invention is on the impact suppressing lung cancer cell growth and apoptosis thereof
80 healthy mices choosing body weight 18-23g are divided into 8 groups at random, be respectively blank group, lotus tumor matched group, five experimental grouies of the embodiment of the present invention one to embodiment five and the Chinese herbal medicine administration group of certain commercially available treatment pulmonary carcinoma, 8 treated animals divide cage to feed, after adaptability feeds 1 week, lotus tumor matched group, experimental group and administration group inoculation tumor cell suspension, every mice right axil subcutaneous vaccination tumor cell suspension 0.2mL, and start gastric infusion after Yu Yizhou; Blank group and lotus tumor matched group adopt normal saline gavage, and consumption is 0.2mL/(, and d) consumption of five experimental grouies is 0.5g/Kg, and in Chinese herbal medicine administration group, the concentration of Chinese herbal medicine is 4g/mL, consumption be 0.2mL/(d), gavage three weeks altogether.
In experimentation, observe the mice mental status, active situation, response situation and depilation etc.; After experiment terminates, measure the weight of animals, get its meansigma methods, and put to death animal, solution cuts tumor tissues, takes out rapidly tumor tissue and weighs, calculate each group of galassing average of sauntering, and carry out t inspection process, calculate tumour inhibiting rate according to the following formula: tumour inhibiting rate=[1-experimental group average tumor weight/lotus tumor matched group is on average sauntered heavily] × 100%, experimental result is as shown in table 4.
Table 4 drop pill is to suppression lung cancer cell growth and apoptotic effect result thereof
Remarks: *---compared with lotus tumor matched group, P<0.05, * *---compared with lotus tumor matched group, P<0.01;
#---compared with blank group, P<0.05.
In experimentation, 8 groups of mice-transplanted tumors are all survived and grow, and in medication process, each group mice is movable normal, and flexibly, hair is smooth glossy in reaction, and spirit is good, withered without hair color, suffer from diarrhoea, become thin.As can be seen from Table 4, compared with blank group, the Mouse Weight of lotus tumor matched group declines obvious, and mice becomes thin gradually; Compared with lotus tumor matched group, the Mouse Weight of five kinds of drop pill experimental grouies of the embodiment of the present invention one to embodiment five increases gradually, and body weight increases obviously, replys normal gradually; Meanwhile, its average tumor is heavy also significantly to be reduced, and inhibitory rate is to more than 70%; This is compared with the Chinese herbal medicine group of commercially available treatment pulmonary carcinoma, also concrete significantly advantage, and the weightening finish of its mice is more, and average tumor is heavy lighter, and tumour inhibiting rate is higher; Therefore, croton seed alkaloid drop pill of the present invention has the effect significantly suppressing the growth of lotus tumor.
Experimental example 4: clinical trial
Patient data
Random selecting 30-65 year Patients with Non-small-cell Lung 200 example, wherein, man 120 example, female 80 example, the mean age is 48.7 years old, the course of disease 3 months to 10 years, average course of disease 4.8 years; The last fortnight of test, Continuous Observation is carried out to this crowd, record symptom and change, two groups are divided into according to the method for M-F, ratio of age and course of disease balanced proportion, be respectively matched group and treatment group, often organize each 100 examples, do not have diversity statistically between two groups of patients, two groups of patients all meet the diagnostic criteria of pulmonary carcinoma; These two groups of patients are before accepting this treatment, and all once with the Therapeutic Method such as Western medicine or Chinese medicine, but effect is not remarkable, has increased the weight of the misery of patient.
Therapeutic scheme
Matched group: patient takes the Chinese herbal medicine of certain commercially available treatment pulmonary carcinoma respectively orally, is decocted in water for oral dose, one after each meal, and every day 2 times, each 50mL 1 month is 1 course for the treatment of, takes 6 courses for the treatment of continuously;
Treatment group: patient is croton seed alkaloid drop pill of the present invention for oral administration respectively, and one after each meal, every day 2 times 2 weeks is 1 course for the treatment of, takes 6 courses for the treatment of continuously.
All experimenters all must not merge the medicine using other treatment pulmonary carcinoma any and the medicine that may affect clinical efficacy and untoward reaction evaluation at duration of test.
Efficacy assessment standard
Complete incidence graph (CR): all visible focuses disappear completely, at least maintain more than 4 weeks;
Partial rcsponse (PR): the product in longest diameter of tumor and maximum perpendicular footpath reduces more than 50%, is in progress without other focuses, occurs without any new focus;
Stable disease unchanged (SD): the product minimizing in longest diameter of tumor and maximum perpendicular footpath is less than 50%, or increase is no more than 25%, occurs without any new focus;
Progress (PD): the product in longest diameter of tumor and maximum perpendicular footpath is greater than 25%;
CR+PR is total effective rate.
Therapeutic effect
Table 5 clinical treatment outcome summary sheet
Clinical observation result
As can be seen from Table 5, compared with matched group, drop pill of the present invention all has good curative effect to treatment pulmonary carcinoma, and clearly, complete remission rate obviously raises advantage, and total effective rate reaches 95%; Mild in medicine property and, gentleness easily takes, and significantly reduces the misery of patient; Instant effect, stable curative effect, short treating period, has no side effect.
Model case
Case 1: field, female, 43 years old, foreign enterprise employee, was busy with one's work, and pressure is large, the not free conditioning of cold cough; In the last few years, hoarseness, felt sick, uncomfortable in chest weak, and Upper abdominal pain is uncomfortable, and cough is more and more serious, is pulmonary carcinoma through hospital diagnosis.Once did chemotherapy and radiation in hospital, because somatic reaction is comparatively large, headache, alopecia, nausea and vomiting, thus stop.Take drop pill of the present invention, each 1 time sooner or later, one after each meal; After taking 2 courses for the treatment of, patient's degree of coughing alleviates, the cycle stretch-out of cough; Continue to take 2 courses for the treatment of, Upper abdominal pain obviously alleviates, and hoarseness symptom is significantly improved; Then take 2 courses for the treatment of, patient's focal symptom disappears completely, and appetite increases, in high spirits; Follow up a case by regular visits to 2 years, focus is stablized, and quality of life ensures.
Case 2: Lee, man, 36 years old, builder, working strength is large, and dust is many, and operation at ordinary times does not note personal protection; In the last few years, started to occur cough, expectoration and dyspnea symptom; Hospital's breast CT inspection shows right hilar shadow and increases and bottom right lung patch shape shade, and tracheoscopy visible bottom right lung dorsal segment opening neoplasm, biopsy pathology is shown for pulmonary carcinoma.Once took Chinese herbal medicine and the Western medicine of a lot for the treatment of pulmonary carcinoma, and because these medicine flavour of a drug are strong, took difficulty, and take effect slow, side effect is large, brings more misery to patient.Take drop pill of the present invention, each 1 time sooner or later, one after each meal; After taking 2 courses for the treatment of, patient respiratory difficulty symptom starts to alleviate, and cough degree alleviates, the cycle stretch-out of cough; Continue to take 2 courses for the treatment of, cough and expectoration symptom obviously alleviate, and dyspnea symptom is obviously improved; Then take 2 courses for the treatment of, the visible focal symptom of patient disappears completely, and in high spirits, health is strong; Follow up a case by regular visits to 1 year, focus is stablized, and quality of life ensures.
Case 3: Zhang, man, 65 years old, retired worker, patient's long-term smoking, health is always more weak, chronic cough; In the last few years, the frequency of cough obviously increased, and the time that cough continues is long, Upper abdominal pain, and dyspnea is pulmonary carcinoma through hospital diagnosis; Once opened breast inspection, found that pneumonopathy extensively shifted, can not excision; Postoperative household's emotion is very poor, and patient is also painful abnormal.Take drop pill of the present invention, each 1 time sooner or later, one after each meal; After taking 2 courses for the treatment of, patient's degree of coughing alleviates, the cycle stretch-out of cough; Continue to take 2 courses for the treatment of, Upper abdominal pain alleviates, and dyspnea symptom is obviously improved; Then take 2 courses for the treatment of, minimal invasive treatment takes care of oneself, and focus is without continuing transfer again, stable disease; Follow up a case by regular visits to 1 year, take a turn for the better before focus transfer comparatively, be emotionally stable.
Beneficial effect of the present invention: the present invention utilizes the pure mixing under the effect of PEG 8000 of croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid and makes the drop pill medicine for the treatment of pulmonary carcinoma, the medicinal liquid state of this drop pill is moderate, roundness is moderate, smooth surface, hardness is moderate, and content of dispersion is more, its water solublity, dispersibility and good stability, taking convenience, can use throughout the year; The present invention utilizes croton seed alkaloid suppress the growth of Lung Adenocarcinoma A 549 Cell by Bax/Bcl-2 approach and promote its apoptosis, croton seed alkaloid and other raw material are worked in coordination with mutually, drug effect complements each other, bring out the best in each other, through focus depths, nurse one's health patient body inside function, gained drop pill has the effect significantly suppressing lung cancer cell growth and promote its apoptosis, serves the effect for the treatment of pulmonary carcinoma comprehensively; Its good effect, instant effect, dose is few, mild in medicine property and, gentle easily clothes, secondary injury can not be caused to patient body, effectively can alleviate cough, uncomfortable in chest, the symptom of puzzlement lung cancer patient such as to feel suffocated, the quality of life of patient can be significantly improved, extend the existence time limit, for clinical treatment pulmonary carcinoma provides a kind of new direction.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (7)
1. the application of croton seed alkaloid in the medicine of preparation treatment pulmonary carcinoma, it is characterized in that, described medicine comprises the raw material of following weight portion:
Croton seed alkaloid 5-10 part, naringin 1-2 part, Radix Scutellariae alkaloid 2-4 part, rutin 0.5-2 part, Liriodendron alkaloid 1-2 part, Rhizoma Coptidis alkaloid 2-5 part, dehiscent fruit potato saponin 1-3 part, Radix Glycyrrhizae alkaloid 2-6 part.
2. the application of croton seed alkaloid according to claim 1 in the medicine of preparation treatment pulmonary carcinoma, it is characterized in that, described medicine comprises the raw material of following weight portion:
Croton seed alkaloid 8 parts, naringin 1.5 parts, Radix Scutellariae alkaloid 3 parts, rutin 1.5 parts, Liriodendron alkaloid 1.5 parts, Rhizoma Coptidis alkaloid 3 parts, dehiscent fruit potato saponin 2 parts, Radix Glycyrrhizae alkaloid 4.5 parts.
3. the application of croton seed alkaloid according to claim 1 and 2 in the medicine of preparation treatment pulmonary carcinoma, is characterized in that:
The dosage form of described medicine is drop pill type.
4. the application of croton seed alkaloid according to claim 3 in the medicine of preparation treatment pulmonary carcinoma, is characterized in that:
Described drop pill type medicine also comprises PEG 8000 60-100 weight portion.
5. a preparation method for medicine according to claim 4, is characterized in that, comprises the following steps:
1) taking polyethylene glycol 8000, is heated to melting, stirs, and makes substrate;
2) get croton seed alkaloid, naringin, Radix Scutellariae alkaloid, rutin, Liriodendron alkaloid, Rhizoma Coptidis alkaloid, dehiscent fruit potato saponin and Radix Glycyrrhizae alkaloid, grinding, screening, obtains mixed-powder;
3) by step 2) gained mixed-powder adds step 2) in gained substrate, fully stir, make uniform medicinal liquid;
4) step 3) gained medicinal liquid is instilled in the dimethicone of 2-4 DEG C under the heat-retaining condition of 85-95 DEG C, take out after drop pill molding, wipe the dimethicone on drop pill surface with absorbent paper, naturally dry, to obtain final product.
6. the preparation method of medicine according to claim 5, is characterized in that:
In described step 4), drip speed and drip/min for 30-60, dripping a distance is 2.0-4.0cm.
7. the preparation method of medicine according to claim 6, is characterized in that:
In described step 1), PEG 8000 adopts the heating in water bath of 85-95 DEG C.
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CN1899358A (en) * | 2005-07-22 | 2007-01-24 | 张晴龙 | Croton alkaloid injection and its preparing method |
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CN102335234A (en) * | 2011-08-08 | 2012-02-01 | 南京林业大学 | Alkaloid extract of trembling poplar as well as extraction method and application thereof |
CN103255196A (en) * | 2013-05-31 | 2013-08-21 | 中国人民解放军第三〇二医院 | Method for detecting effect of Coptis chinensis alkaloid monomer on tumor cells |
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CN1899358A (en) * | 2005-07-22 | 2007-01-24 | 张晴龙 | Croton alkaloid injection and its preparing method |
CN101384575A (en) * | 2005-12-23 | 2009-03-11 | Q生物有限公司 | Tiglien-3-one derivatives |
CN102335234A (en) * | 2011-08-08 | 2012-02-01 | 南京林业大学 | Alkaloid extract of trembling poplar as well as extraction method and application thereof |
CN103255196A (en) * | 2013-05-31 | 2013-08-21 | 中国人民解放军第三〇二医院 | Method for detecting effect of Coptis chinensis alkaloid monomer on tumor cells |
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Application publication date: 20151230 |