CN109045039A - Pharmaceutical formulation and the application for treating lung cancer - Google Patents

Pharmaceutical formulation and the application for treating lung cancer Download PDF

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Publication number
CN109045039A
CN109045039A CN201810705718.9A CN201810705718A CN109045039A CN 109045039 A CN109045039 A CN 109045039A CN 201810705718 A CN201810705718 A CN 201810705718A CN 109045039 A CN109045039 A CN 109045039A
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pharmaceutical formulation
lung cancer
trihydroxydammar
12beta
6alpha
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Inventor
范代娣
董杨芳
段志广
马晓轩
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XI'AN GIANT BIOGENE TECHNOLOGY Co Ltd
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XI'AN GIANT BIOGENE TECHNOLOGY Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

It include 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib and pharmaceutically acceptable auxiliary material the present invention relates to the pharmaceutical formulation for the treatment of lung cancer and application, the pharmaceutical formulation, the molar ratio of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib is (2:1)-(4:1).The pharmaceutical formulation can significantly inhibit the growth of proliferation of lung cancer cells and Pulmonary carcinoma nude mice transplantable tumor, effect is substantially better than the same dose of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranosides or Gefitinib independent medication, after illustrating that the two is used in combination, with significant synergistic function, toxic side effect is low, and clinical landscapes application is good.

Description

Pharmaceutical formulation and the application for treating lung cancer
Technical field
The invention belongs to biological chemical fields, and in particular to a kind of pharmaceutical formulation for treating lung cancer and application.
Background technique
Lung cancer is one of malignant tumour most aggressive in the world, morbidity and mortality in malignant tumour most It is high.According to the lung neoplasm histologic classification method that the World Health Organization in 1981 proposes, lung cancer can be divided into two types: cellule lung Cancer (SCLC) and non-small cell lung cancer (NSCLC).NSCLC is histologically further divided into gland cancer again, prognosis of squamous cell lung cancer and Three hypotypes of maxicell lung cancer, account for the 80-90% of whole cases of lung cancer.The prognosis very severe of lung cancer, most patients with lung cancer are just Advanced stage is already belonged to when examining, and loses optimal treatment chance, survival rate is usually less than 15% within 5 years.
Chemotherapeutics Gefitinib is the conventional medicament for treating lung cancer, also kills machine while killing tumor cell Body normal cell lacks targeting, causes very major injury to hemopoietic system, immune system etc..In addition, tumor therapy clinical is studied Show that drug resistance can be generated using the chemotherapeutics of single inhibition growth of tumour cell for a long time.As treatment tumour is related Research approach deepens continuously, and drug combination becomes one of the hot spot of therapeutic field of tumor in recent years.A large amount of clinical and experiment Studies have shown that combination drug thexapy has special efficacy in terms of the prevention and treatment of tumour and rehabilitation, have compared with traditional single therapy Lot of advantages, such as overcome tumor drug resistance, synergy, reduce toxic side effect.
Main active of the ginsenoside as plants such as Araliaceae ginseng, Radix Notoginseng, American Ginsengs, be broadly divided into Lower three classes: oleanolic acid type ginsenoside, protopanaxadiol-type's ginsenoside, protopanaxatriol type ginsenoside.Numerous studies Show that various ginsenosides have its unique pharmacological action, mainly has and tumor cell proliferation, inducing cell is inhibited quickly to wither It dies, anti-immunity, anti-aging, platelet aggregation-against and improve cardiovascular and cerebrovascular blood supply insufficiency etc..3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside is a kind of protoplast's ginseng Three alcohol type ginsenosides, chemical formula are molecular formula: C36H60O8, molecular weight: 620.86, alcohol-soluble is stronger, water-soluble low.The change Close object be main degradation products of the ginsenoside Re in body enteron aisle, be natural three alcohol type ginsenosides in vivo really absorb and The entity of performance.3beta,6alpha,12beta-Trihydroxydammar-20's content in natural ginseng is few, can not largely separate acquisition.It there is no producer can be at present Largely prepare.Some researches show that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside can significantly inhibit lung cancer, the proliferation of liver cancer cells in recent years.However So far, the report of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and chemotherapeutics Gefitinib drug combination effect of anti-lung cancer be there is no both at home and abroad at present.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical formulation for treating lung cancer and applications, are combined 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and chemotherapy Drug Gefitinib plays the synergistic function of the two as the effective component of anti-lung-cancer medicament.
The technical scheme adopted by the invention is as follows:
The pharmaceutical formulation for treating lung cancer, it is characterised in that:
The pharmaceutical formulation includes 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib.
The molar ratio of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib is (2:1)-(4:1).
Purity >=95% of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, purity >=98% of Gefitinib.
It include pharmaceutically acceptable auxiliary material in pharmaceutical formulation.
Auxiliary material is selected from Sodium Hyaluronate, sodium alginate, chitosan or collagen.
The application of the pharmaceutical formulation for the treatment of lung cancer as mentioned, it is characterised in that:
The effective component of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib combination as preparation treatment lung-cancer medicament.
The dosage of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside is 20-120 mg/kg, and the dosage of Gefitinib is 7-45 mg/kg.
The pharmaceutical formulation is oral agents or injection.
The oral agents are hard capsule, soft capsule, slow release capsule, sugar coated tablet, pulvis, granule, dripping pill, water honey Ball, syrup or oral solution；
The injection is solution-type, suspension type, emulsion type or freeze-dried powder.
The invention has the following advantages that
The present invention provides a kind of pharmaceutical formulation for treating lung cancer, it contains 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib, and pharmaceutically Acceptable auxiliary material.The pharmaceutical formulation can significantly inhibit the growth of proliferation of lung cancer cells and Pulmonary carcinoma nude mice transplantable tumor, effect Fruit is substantially better than the same dose of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranosides or Gefitinib independent medication, after illustrating that the two is used in combination, has significant Synergistic function, toxic side effect is low, and clinical landscapes application is good.
Detailed description of the invention
Fig. 1 is 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication and drug combination 48h to lung cancer NCI-H460 cell Proliferation Inhibiting effect.
Fig. 2 is 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication and the suppression that drug combination 48h is proliferated lung cancer A549 cell Production is used.
Fig. 3 is 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication and drug combination to nude mouse tumor volume and changes of weight Influence.
Fig. 4 be 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib individually contaminate and combined exposure to healthy mice amount of drinking water, food ration and The influence of changes of weight.
Fig. 5 is 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib is individually contaminated and combined exposure is to healthy mice liver function and renal function Influence.
Fig. 6 is 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib is individually contaminated and combined exposure is to healthy mice liver function and renal function Influence.
Specific embodiment
The present invention will be described in detail With reference to embodiment.
The present invention relates to a kind of pharmaceutical formulations for treating lung cancer, include 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib, ginsenoside The molar ratio of Rk3 and Gefitinib is (2:1)-(4:1), purity >=95% of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, the purity of Gefitinib >= 98%。
It include pharmaceutically acceptable auxiliary material in pharmaceutical formulation.Auxiliary material is selected from Sodium Hyaluronate, sodium alginate, chitosan Or collagen.
The combination Internet of Things of above-mentioned 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib can be used as preparation treatment lung-cancer medicament it is effective at Point.The dosage of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside is 20-120 mg/kg, and the dosage of Gefitinib is 7-45 mg/kg.
The pharmaceutical formulation is oral agents or injection.Oral agents are hard capsule, soft capsule, slow release capsule, sugar Garment piece, pulvis, granule, dripping pill, water-honeyed pill, syrup or oral solution；The injection is solution-type, suspension type, milkiness Liquid type or freeze-dried powder.
1 3beta,6alpha,12beta-Trihydroxydammar-20's capsule of embodiment
Capsule (10000,3beta,6alpha,12beta-Trihydroxydammar-20's content: 80mg/, Gefitinib content 30mg/) are made according to following ratio
2 3beta,6alpha,12beta-Trihydroxydammar-20's tablet of embodiment
According to following ratio be made tablet (10000,3beta,6alpha,12beta-Trihydroxydammar-20's content: 120mg/, Gefitinib content 45mg/ Grain)
3 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside of embodiment and Gefitinib independent medication and drug combination 48h are to lung cancer NCI-H460 cell Proliferation Inhibiting effect
By lung cancer NCI-H460 cell inoculation in sterile 96 orifice plate, after cultivating 48h, the ginseng soap that concentration is 0-100 μM is added Glycosides Rk3 or 0-50 μM of Gefitinib, 0-100 μM of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and 0-50 μM of Gefitinib drug combination.Control group adds Enter isometric 1640 culture medium, 5 multiple holes are arranged in each concentration.After cultivating 48h, 5 μ g/mL MTT are added in every hole, continue to train Support 4h.150 μ L DMSO, slow oscillation 10min are added, make it dissolve the bluish violet crystallization Formazan of generation.In 570 nm The corresponding absorbance A value in each hole is detected at place, and calculates cell inhibitory rate using following formula:
Inhibiting rate=(1- administration group average A-value/control group average A-value) × 100%
By Fig. 1 it is found that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication lung cancer NCI-H460 cells show is gone out it is certain 3beta,6alpha,12beta-Trihydroxydammar-20's (0-100 μM) and Gefitinib (0-50 μM) drug combination it is right can effectively to be promoted its by inhibiting effect The inhibiting rate of lung cancer NCI-H460 cell, and with dose dependent.And it in 3beta,6alpha,12beta-Trihydroxydammar-20's (0-100 μM) and lucky non-replaces When Buddhist nun (0-50 μM) collective effect, the inhibitory effect of drug combination is substantially better than 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication The summation of effect illustrates that the two drug combination has played synergistic effect.
4 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside of embodiment and Gefitinib independent medication and drug combination 48h are proliferated lung cancer A549 cell Inhibiting effect
Lung cancer A549 cell is inoculated in sterile 96 orifice plate, after cultivating 48h, addition concentration is 0-100 μM of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Or 0-50 μM of Gefitinib, 0-100 μM of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and 0-50 μM of Gefitinib drug combination.Control group addition etc. 5 multiple holes are arranged in the 1640 culture medium of volume, each concentration.After cultivating 48h, 5 μ g/mL MTT are added in every hole, continue to cultivate 4h.150 μ L DMSO, slow oscillation 10min are added, make it dissolve the bluish violet crystallization Formazan of generation.At 570 nm The corresponding absorbance A value in each hole is detected, and calculates cell inhibitory rate using following formula:
Inhibiting rate=(1- administration group average A-value/control group average A-value) × 100%
As shown in Figure 2,3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication show certain inhibition work to lung cancer A549 cell With can effectively promote it to lung cancer for 3beta,6alpha,12beta-Trihydroxydammar-20's (0-100 μM) and Gefitinib (0-50 μM) drug combination The inhibiting rate of A549 cell, and with dose dependent.And in 3beta,6alpha,12beta-Trihydroxydammar-20's (0-100 μM) and Gefitinib (0-50 μM) collective effect when, the inhibitory effect of drug combination is substantially better than the total of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication effect With both illustrate that drug combination has played synergistic effect.
5 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside of embodiment and Gefitinib independent medication and drug combination induce lung cancer NCI-H460 cell Apoptotic effect
By lung cancer NCI-H460 cell inoculation in sterile 6 orifice plates, after culture for 24 hours, the ginsenoside that concentration is 0-50 μM is added Rk3 or 0-25 μM of Gefitinib, 0-50 μM of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and 0-25 μM of Gefitinib drug combination.Control group is added 5 multiple holes are arranged in isometric 1640 culture medium, each concentration.Continue after cultivating 48h, ice-cold PBS be added and washs 2-3 times, 1 × Binding Buffer buffer is added, uniformly, suitable AV/PI mixing dye liquor is added dropwise in piping and druming, is protected from light and is incubated for 15min, makes With flow cytomery Apoptosis.
Fig. 3 is to be induced using Flow cytometry 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication and drug combination The experimental result picture of NCI-H460 Apoptosis obtains being made of cell histogram four quadrants, and region Q1 indicates experimental implementation Occurs the cell of mechanical damage in the process, region Q2 indicates that the cell of late apoptic occurs, and region Q3 indicates that functional form is normal Cell, region Q4 indicate occur early apoptosis cell.From the figure 3, it may be seen that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication energy Enough certain apoptotic effect occurs for induction lung cancer NCI-H460 cell, and the cell percentage of generation apoptosis representated by the Q4 of region is in The trend being now slowly increased, 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib drug combination promote the percentage of lung cancer apoptotic cell significantly to mention It rises.When 3beta,6alpha,12beta-Trihydroxydammar-20's concentration is 50 μM, the early apoptosis rate of NCI-H460 cell is to wither the early stage of 14.12%(control group 3.12%) dying rate is；When Gefitinib concentration is 25 μM, NCI-H460 early apoptosis of cells rate is 17.45%(control group 3.67%) early apoptosis rate is；When the concentration of the two pharmaceutical formulation is 75 μM, NCI-H460 early apoptosis of cells rate is The early apoptosis rate of 45.38%(control group is 3.63%), further to prove that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib drug combination promote Lung carcinoma cell accelerates apoptosis, to play the role for the treatment of lung cancer.
The inhibition of 6 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside of embodiment and Gefitinib independent medication and drug combination to transplantable lung cancer model Effect
Male BALB/c nude mice is raised at room temperature, after it adapts to environment, is inoculated with NCI-H460 cell, every nude mice to it Inject 3-4 × 106A cell.After inoculation 7 days, the observation left armpit of nude mice is subcutaneous, and there is grain of rice size at discovery nude inoculation position Tubercle generates.Continue to raise, tumor size is more than 100 mm3When, tumor size and the biggish nude mice of weight differences are rejected, and will Remaining tumor bearing nude mice is grouped at random.All tumor bearing nude mices are divided into following 4 groups by this experiment: (1) model group；(2) 40 Mg/kg Rk3 group；(3) 15 mg/kg Gefitinib groups；(4) (40 mg/kg Rk3 and 15 mg/kg are lucky non-to be replaced drug combination group Buddhist nun).Model group gives the mixed liquor (volume ratio 1:1) of polyethylene glycol and water.Remaining group is filled according to the weight of tumor bearing nude mice Stomach administration, is administered once a day.Every weight, gross tumor volume and the changes in diet of 7 days measurement tumor bearing nude mices, and observation note in time Record.After 35 days, stop administration, put to death all mouse, removes tumor mass, weigh, record one by one and collect.
By Fig. 4 A it is found that comparing with model group, when being administered 35 days, 3beta,6alpha,12beta-Trihydroxydammar-20's group and Gefitinib group are naked to lung cancer The inhibiting rate of mouse transplantable tumor is respectively 21.22% and 28.66%, shows 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib independent medication to lung cancer Transplanted tumor in nude mice has certain inhibiting effect.Drug combination group can slow down the growth of nude mouse tumor volume, corresponding tumour inhibiting rate It is 67.31%, there is remarkable result.It is compared with model group, the trend gradually increased is presented in the weight that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside organizes nude mice, Reduction trend is presented in the weight of Gefitinib group nude mice, and drug combination group nude mice weight does not have notable difference, shows it to nude mice Safety it is higher (Fig. 4 B).In conclusion drug combination group can obviously hinder the growth of Pulmonary carcinoma nude mice transplantable tumor, inhibit Rate is significantly higher than 3beta,6alpha,12beta-Trihydroxydammar-20's group and Gefitinib group, and shows less toxic side effect to nude mice, illustrates 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside Synergistic effect has been played with Gefitinib drug combination.
The internal safety evaluatio of 7 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside of embodiment and Gefitinib independent medication and drug combination
Male and healthy ICR mouse is raised in room temperature environment, free diet, relative humidity 50-60%, 12h daytime/12h are black Night.Raising 1 week, after it adapts to environment, fasting 12h.After 12h, mouse is randomly divided into 4 groups: (1) control group；(2) 40 mg/ Kg 3beta,6alpha,12beta-Trihydroxydammar-20's group；(3) 15 mg/kg Gefitinib groups；(4) (40 mg/kg Rk3 and 15 mg/kg are lucky for drug combination group It is non-to replace Buddhist nun).Above 4 groups are administered in a manner of stomach-filling.After 6h is administered, cancel fasting, it is normal to feed mouse 14 days.Observe mouse drink Water is ingested, the variation of weight and hepatic and renal function.
It is compared as shown in Figure 5 with control group, after contaminating, 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside organizes amount of drinking water, food ration and the body of mouse Weight is not substantially change, and amount of drinking water, food ration and the weight of Gefitinib group mouse occur significantly to change, drug combination Amount of drinking water, food ration and the weight of group mouse are not substantially change.
It will be appreciated from fig. 6 that comparing with control group, 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside organizes paddy in the liver weight, kidney weight, serum of mouse Creatinine content is not substantially change in pyruvic transaminase content and serum, liver weight, the kidney of Gefitinib group mouse Creatinine content occurs slightly to change in glutamic-pyruvic transaminase content and serum in dirty weight, serum, drug combination group mouse Liver weight, kidney weight, creatinine content is not substantially change in glutamic-pyruvic transaminase content and serum in serum. It can be seen that 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib drug combination show certain safety to healthy mice.
The contents of the present invention are not limited to cited by embodiment, and those of ordinary skill in the art are by reading description of the invention And to any equivalent transformation that technical solution of the present invention is taken, all are covered by the claims of the invention.

Claims (9)

1. the pharmaceutical formulation for treating lung cancer, it is characterised in that:
The pharmaceutical formulation includes 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib.
2. the pharmaceutical formulation for the treatment of lung cancer according to claim 1, it is characterised in that:
The molar ratio of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib is (2:1)-(4:1).
3. the pharmaceutical formulation for the treatment of lung cancer according to claim 1, it is characterised in that:
Purity >=95% of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, purity >=98% of Gefitinib.
4. the pharmaceutical formulation for the treatment of lung cancer according to claim 1, it is characterised in that:
It include pharmaceutically acceptable auxiliary material in pharmaceutical formulation.
5. the pharmaceutical formulation for the treatment of lung cancer according to claim 4, it is characterised in that:
Auxiliary material is selected from Sodium Hyaluronate, sodium alginate, chitosan or collagen.
6. the application of the pharmaceutical formulation for the treatment of lung cancer as described in claim 1, it is characterised in that:
The effective component of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside and Gefitinib combination as preparation treatment lung-cancer medicament.
7. the application of the pharmaceutical formulation for the treatment of lung cancer according to claim 6, it is characterised in that:
The dosage of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside is 20-120 mg/kg, and the dosage of Gefitinib is 7-45 mg/kg.
8. the application of the pharmaceutical formulation for the treatment of lung cancer according to claim 6, it is characterised in that:
The pharmaceutical formulation is oral agents or injection.
9. the application of the pharmaceutical formulation for the treatment of lung cancer according to claim 8, it is characterised in that:
The oral agents be hard capsule, soft capsule, slow release capsule, sugar coated tablet, pulvis, granule, dripping pill, water-honeyed pill, Syrup or oral solution；
The injection is solution-type, suspension type, emulsion type or freeze-dried powder.
CN201810705718.9A 2018-07-02 2018-07-02 Pharmaceutical formulation and the application for treating lung cancer Pending CN109045039A (en)

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CN106466299A (en) * 2015-08-19 2017-03-01 上海本素医药科技有限公司 Blank liposome with ginsenoside as membrane material, its preparation method and application

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