CN109999158A

CN109999158A - A kind of pharmaceutical composition and its application for treating lung cancer

Info

Publication number: CN109999158A
Application number: CN201811472585.1A
Authority: CN
Inventors: 盘其伟
Original assignee: Shenzhen Qianhai Wushiyuan Biotechnology Co Ltd
Current assignee: Shenzhen Qianhai Wushiyuan Biotechnology Co Ltd
Priority date: 2018-12-04
Filing date: 2018-12-04
Publication date: 2019-07-12

Abstract

The present invention relates to a kind of pharmaceutical compositions for treating lung cancer, and its application in the drug of preparation treatment lung cancer.The composition is made of the following Chinese medicine material of quality proportioning: 30~40 parts of naze, 20~30 parts of stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, 5~15 parts of American Ginseng, 20~40 parts of Radix Astragali, 5~15 parts of Schisandra chinensis, 15~35 parts of ramulus cinnamomi, 5~10 parts of gun additioner, 10~20 parts of Semen Cuscutae, 10~20 parts of the fruit of glossy privet, 1~6 part of pilose antler, 10~20 parts of HERBA EPIMEDII, 10~20 parts of the root of straight ladybell, 10~20 parts of Radix Ophiopogonis, 20~40 parts of oldenlandia diffusa, 10~20 parts of the root bark of white mulberry, 10~20 parts of Radix Rehmanniae, 20~40 parts of Prunella vulgaris, 10~20 parts of Radix Salviae Miltiorrhizae, 10~20 parts of radix paeoniae rubra, 5~15 parts of Fructus Aurantii, 5~15 parts of Radix Curcumae, 20~40 parts of black nightshade, 10~20 parts of edible tulip, 20~40 parts of Sculellaria barbata, 5~15 parts of lily, peach kernel 5~1 5 parts.Chinese medicine compound prescription of the present invention has apparent killing effect for the Lu-csf-1 of in vitro culture and the primary adenocarcinoma of lung of mouse, and can activate mouse immune system, and good application prospect is embodied in terms of lung cancer therapy.

Description

A kind of pharmaceutical composition and its application for treating lung cancer

(1) technical field

The present invention relates to a kind of pharmaceutical compositions for treating lung cancer, and its application in the drug of preparation treatment lung cancer.

(2) background technique

It is reported that cancer was once more than the cardiovascular lethal first big cause of the death for having become China resident, and in all cancers In disease, lung cancer ranks first in all cancers.Lung cancer is worldwide the first big tumour, " world's tumour report in 2014 " Data show, newly-increased 1,800,000 people of patients with lung cancer in 2012, the 13% of Zhan Suoyou tumour；Lung cancer death number increases by 1,600,000 People accounts for the 20% of whole death rates.New cases more than 1/3 are from China, and annual new cases about 73.3 ten thousand, death are about 59.1 ten thousand, the lung cancer in China death rate rises 465% between Past 30 Years.The cure rate of lung cancer is very low, only 10-15%.China Atmosphere pollution it is serious, the disease incidence of the following lung cancer will remain high, need research and development lung cancer therapy new method.

Currently, traditional lung cancer therapy method includes operation, radiotherapy and chemotherapy, however they are all lacked in the presence of be difficult to overcome It falls into.And the treatment of small-molecule drug is pure the problems such as high toxic side effect is with non-specificity.Using EGFR and VEGF as the target of target spot It is not fully up to expectations to the therapeutic effect to the patients with lung cancer being mutated there are Kras such as antibody drug, and generate hypertension, thrombus bolt The toxic side effects such as plug, bleeding episode and drug resistance.The white man's patients with lung cancer for especially only accounting for 19% to EGFR mutation rate has very much The targeted therapy medicine EGFR tyrosine kinase inhibitor of effect but accounts for 48% East Asia female patients to its mutation rate and has little effect.Most Monoclonal antibody (Pembrolizumab/Nivolumab) drug for PD-1 and PD-L1 of nearly U.S. FDA approval, to controlling Advanced stage squamous non-small cell type lung cancer first-line treatment is treated, and has certain curative effect；But it is low to Small Cell Lung Cancer With Selective effective percentage, it plays Effect is relatively slow and there are apparent individual treatment difference on effect.Therefore, lung cancer does not have specific drug, this is very severe asks Topic.

Standardized application of the Chinese medicine in terms of lung cancer smelting treatment, Chinese medicine treatment distinguish void under dialectical theoretical concrete guide It is real evil that just on theoretical point view that is whole and locally combining, anticancer therapy and treatment of strengthening the body resistance to consolidate the constitution are combined, Coryza Treated by Syndrome Differentiation with Treatment according to differentiation of diseases combines.The etiology and pathogenesis of lung cancer morbidity is healthy tendency internal weakness, the solidifying poison of phlegm gathers and internal organs imbalance of yin and yang, dialectical point specific Type has as many as 5~6 kinds again, but carefully studies, and searches to the bottom, then is " deficiency of vital energy ".Healthy tendency internal weakness is not required to illustrate when being the deficiency of vital energy；Phlegm Solidifying poison is poly-, because being then water-damp retention, unsaturated vapor and transporting is unfavorable causes；Internal organs imbalance of yin and yang, viscera function reduce, and are also gas Void performance.Lung being a delicate viscus, the canopy of the five internal organs, sun is often insufficient, therefore should be based on " deficiency of yang " among its " deficiency of vital energy ".In clinical practice It observes most patients with lung cancer, especially early metaphase, middle and advanced stage patient, shows as that tongue nature is partially fat, and tongue fur is thin white, other are such as The yang-energies asthenic symptoms such as pale complexion, out of strength, burnout are more or less, or obviously or insignificantly there is.Through with warm positive drug supporting healthy energy tune It improves after reason, the basic pathology and disease mechanism of lung cancer is " yang-energy is empty ", and the standardized therefore method of warming yang and benefiting qi is preferably through lung cancer therapy Always.

(3) summary of the invention

The object of the invention is to be to provide a kind of pharmaceutical composition of effectively treatment lung cancer, and its medicine in preparation treatment lung cancer Application in object.

The technical solution adopted by the present invention is that:

A kind of pharmaceutical composition for treating lung cancer, the composition are made of the following Chinese medicine material of quality proportioning: naze 30~40 parts, 20~30 parts of stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, 5~15 parts of American Ginseng, 20~40 parts of Radix Astragali, 5~15 parts of Schisandra chinensis, ramulus cinnamomi 15~35 Part, 5~10 parts of gun additioner, 10~20 parts of Semen Cuscutae, 10~20 parts of the fruit of glossy privet, 1~6 part of pilose antler, 10~20 parts of HERBA EPIMEDII, the root of straight ladybell 10~20 parts, 10~20 parts of Radix Ophiopogonis, 20~40 parts of oldenlandia diffusa, 10~20 parts of the root bark of white mulberry, 10~20 parts of Radix Rehmanniae, Prunella vulgaris 20 ~40 parts, 10~20 parts of Radix Salviae Miltiorrhizae, 10~20 parts of radix paeoniae rubra, 5~15 parts of Fructus Aurantii, 5~15 parts of Radix Curcumae, 20~40 parts of black nightshade, edible tulip 10~20 parts, 20~40 parts of Sculellaria barbata, 5~15 parts of lily, 5~15 parts of peach kernel.

The present invention is with naze, stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, American Ginseng, Radix Astragali, Radix Ophiopogonis, Schisandra chinensis, ramulus cinnamomi, gun additioner, Semen Cuscutae, glossy privet The 20 Six-element Chinese herbal medicine such as son, pilose antler, HERBA EPIMEDII, Radix Ophiopogonis, Radix Rehmanniae, the root of straight ladybell, lily, radix paeoniae rubra, peach kernel, Fructus Aurantii, Sculellaria barbata composition It can treat " the quintic element lung neoplasm compound preparation " of lung cancer, yin-nourishing QI invigorating, cough-relieving dissipating bind, through clinical trial to the immune function of raising Energy, tumor suppression, effect are aobvious most, play important curative effect to supplementing qi and nourishing yin, heat-clearing and detoxifying drug, reducing phlegm and resolving masses, promoting blood circulationization addiction.

Wherein for lily except having QI invigorating to clear away heart-fire, in addition to moistening lung to arrest cough effect, main component contains colchicin, can inhibit oncocyte Mitosis, contained carrotene, vitamin C etc. are also related with tumour is inhibited in lily, and research confirms that the medicine can enhance list The immune function and anti-aging of nucleus.Radix Ophiopogonis can nourishing Yin and promoting production of body fluid, antibechic hemostasis, external tumour inhibiting rate is up to 44%, Radix Ophiopogonis pair Animal lung cancer and gland cancer have obvious inhibiting effect, Pulmonary metastasis focuses can be made to reduce, and lymphocyte transformation and cell activity improve.Half Lotus is also the lung channel key medicine with resolving hard lump.In addition the functions such as cough-relieving, moistening lung, hemostasis, heat-clearing of other drugs, often obtain More apparent clinical effectiveness.

To lung cancer examine smelting research it is more common with tongue picture and channels and collaterals, acupuncture point diagnosis.It is ground by a large amount of clinical lingual diagnosis observations To study carefully, it was demonstrated that lung cancer shows as tongue is dim-purple, tongue body hypertrophy more, and there are crackle, side print with teeth in surface, and sublingual big channels anger is bent, Tongue fur is how thick greasy.Inventor has found the preferable person of curative effect, tongue picture transformation is more apparent, to propose tongue picture by 30 observation of curative effect Not only there is important value in terms of the early diagnosis to this disease, the efficacy evaluation and Index for diagnosis simultaneously for this disease also have ginseng Examine meaning.Also observe that lung cancer patient early stage is that the light whitish tongue of tongue nature is greasy in clinic, middle and advanced stage tongue nature is partially purple dim, corpulent tongue Greatly, side print with teeth, sublingual large collatereals anger, bending, tongue fur is how thick greasy, and usually patient's nose also shows as purple, this is neoplastic disease The qi depression to blood stasis symptom that people shows, through warming yang and benefiting qi, activating blood and resolving stasis and treating, this performance is better, and the state of an illness is controlled, On the contrary then aggravation.The formation of lung cancer, mainly since healthy tendency is deficient, the heresy of imbalance of yin and yang, the six external factors which cause diseases is taken advantage of a weak point, evil Stagnant a surname's drop mistake department, then lung qi closing, the stagnation of the circulation of vital energy and blood stasis, body fluid not cloth gathers and forms phlegm, phlegm and blood stasis in lung, with the passing of time into accumulating Block.It can be seen that lung cancer is falling ill because of void, reality is caused because of void.Void is disease sheet, actually the mark of disease.Traditional Chinese medicine, which is always worshipped, cures the disease and must ask Its, also advanced lung cancer healthy tendency is deficient particularly evident, and therefore, the treatment to advanced lung cancer should be based on righting, supplemented by eliminating evil For principle of reatment.It is studied by paired observation, the effect for summarizing Yin-nourishing and body fluid promoting, QI invigorating CTD Probe treatment advanced lung cancer is: prolonging Long patient survival；Alleviate and stablize lesion；Improve patients ' life quality；Improve body's immunity.

So treatment take it is dialectical based on, i.e., with lung cancer be diagnose the deficiency of yang foundation, while pass through the differentiation of disease and dialectical phase In conjunction with to carry out diagnosis and treatment based on an overall analysis of the illness and the patient's condition to different manifestations of the deficiency of yang with different patients with lung cancer.Warming yang for dispelling cold medicine emphasizes extraordinary, sheet It is obvious to invent " quintic element lung neoplasm compound preparation " curative effect, obvious impairment of yin dryness-transformation or cancer block there is no to accelerate so far in application process Diffusion etc. complication occur, be not also in the mood for, Liver and kidney function damage etc. toxic side effects.It is studied by precision, it was confirmed that lung cancer is basic The interpretation of the cause, onset and process of an illness " chronic diseases marked by deficiency of vital energy " it is correct.

Preferably, the composition material quality composition is as follows: 35 parts of naze, 25 parts of stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, 10 parts of American Ginseng, Radix Astragali 30 parts, 9 parts of Schisandra chinensis, 20 parts of ramulus cinnamomi, 6 parts of gun additioner, 15 parts of Semen Cuscutae, 15 parts of the fruit of glossy privet, 3 parts of pilose antler, 15 parts of HERBA EPIMEDII, sand Join 15 parts, 15 parts of Radix Ophiopogonis, 30 parts of oldenlandia diffusa, 15 parts of the root bark of white mulberry, 15 parts of Radix Rehmanniae, 30 parts of Prunella vulgaris, 15 parts of Radix Salviae Miltiorrhizae, radix paeoniae rubra 15 Part, 10 parts of Fructus Aurantii, 10 parts of Radix Curcumae, 30 parts of black nightshade, 15 parts of edible tulip, 30 parts of Sculellaria barbata, 10 parts of lily, 10 parts of peach kernel.

The invention further relates to application of the Chinese medicine composition in the drug of preparation treatment lung cancer.

Specifically, the lung cancer is adenocarcinoma of lung.

The beneficial effects are mainly reflected as follows: Lu-csf-1 of the Chinese medicine compound prescription of the present invention in vitro culture There is apparent killing effect with the primary adenocarcinoma of lung of mouse, and mouse immune system can be activated, the body in terms of lung cancer therapy Reveal good application prospect.

(4) Detailed description of the invention

Fig. 1 is preparation technique of traditional Chinese medicine flow chart of the present invention；

Fig. 2 is 3 Chinese medicine object dose-effect curve of embodiment；

Fig. 3 is kunming mice Lung neoplasm picture in embodiment 4；

Fig. 4 is that mouse sarcoidosis of lung manages picture (conventional H E staining analysis) in embodiment 4；Scheming A scale bar is 200 μm, HE ×4；25 μm of B scale bar of figure, HE × 40；

Fig. 5 is mouse spleen CD4 positive lymphocyte content in embodiment 2.

(5) specific embodiment

The present invention is described further combined with specific embodiments below, but protection scope of the present invention is not limited in This:

Embodiment 1:

Formula: naze 35g, stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar 25g, American Ginseng 10g, Radix Astragali 30g, Schisandra chinensis 9g, ramulus cinnamomi 20g, gun additioner 6g, Tu The sub- 15g of silk, fruit of glossy privet 15g, pilose antler 3g, HERBA EPIMEDII 15g, the root of straight ladybell 15g, Radix Ophiopogonis 15g, oldenlandia diffusa 30g, root bark of white mulberry 15g, life Ground 15g, Prunella vulgaris 30g, Radix Salviae Miltiorrhizae 15g, radix paeoniae rubra 15g, Fructus Aurantii 10g, Radix Curcumae 10g, black nightshade 30g, edible tulip 15g, Sculellaria barbata 30g, Lily 10g, peach kernel 10g.

Method:

1, Chinese medicine is checked and accepted: crude drug source document is complete, Packing Sound, it is ensured that quality of medicinal material.

2, it weighs: extracting the dosage of medicinal material used according to compatibility requirement and every extractor, weighed by production work order.

3, wash and slice crush: in wash pond, with clear water to medicinal material Rapid Cleaning, emphasis is to wash away dust, silt particle Equal physical impurities.Some medicinal material shapes are bigger, or partially thick (wooden medicinal material) is not easy to extract, and enters after needing to be sliced crushing Subsequent processing.

4, it extracts: being the ratio of 1:5~10 according to liquid medicine mass ratio, reverse osmosis softened water is added in extractor, then The medicinal material after cleaning and crush is added, extracts water temperature control within the scope of 75~85 DEG C, opens stirring when necessary and extracts, extract Time 1~2 hour, after intermediate samples confirmation reaches extraction effect, terminate abstraction process, into subsequent processing.

5, it is centrifuged deslagging filtering, after extraction, extracting solution is accessed into centrifuge, carries out centrifugation slagging-off.

6, high-efficiency vacuum is concentrated: the extracting solution after centrifugal filtration being injected high-efficiency vacuum concentration systems, carries out being concentrated into 30 ~35Brix.

7, freeze-drying (perhaps spray drying can also): according to requiring that the medical fluid after vacuum concentration is lyophilized or is sprayed It is dry.

8, it is packed and stored: according to specification requirement, in clean area make-up room, after carrying out weighing and bagging according to unified specification, Storage.

Embodiment 2:

Formula: naze 35g, stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar 25g, American Ginseng 10g, Radix Astragali 25g, Schisandra chinensis 12g, ramulus cinnamomi 15g, gun additioner 8g, Semen Cuscutae 15g, fruit of glossy privet 15g, pilose antler 3g, HERBA EPIMEDII 18g, the root of straight ladybell 15g, Radix Ophiopogonis 15g, oldenlandia diffusa 35g, root bark of white mulberry 15g, Radix Rehmanniae 15g, Prunella vulgaris 25g, Radix Salviae Miltiorrhizae 15g, radix paeoniae rubra 15g, Fructus Aurantii 10g, Radix Curcumae 10g, black nightshade 25g, edible tulip 18g, Sculellaria barbata 25g, lily 10g, peach kernel 10g.

Method:

Embodiment 3: the killing effect of Chinese medicine composition in vitro culture human lung carcinoma cell

1.1 experimental method

The measurement of cell activity is realized with classical CCK8 method.The specific method is as follows:

1. collecting logarithmic phase cell (human lung adenocarcinoma epithelial cell line A549), concentration of cell suspension is adjusted, according to every hole 100 μ L is inoculated in 96 hole flat undersides, and bed board makes 6000/hole of cell density to be measured (edge hole is filled with sterile PBS).

2. 5%CO₂, 37 DEG C be incubated for, next day replaces the culture medium (RPMl-1640 culture medium) of the Chinese medicine containing various concentration (every 200 μ L of hole total volume).

3. 5%CO₂, 37 DEG C be incubated for 48 hours, observed under inverted microscope.

4. 20 μ L CCK8 solution are added in every hole, continue to cultivate 4h.

5. measuring the light absorption value in each hole at enzyme-linked immunosorbent assay instrument 450nm, result is recorded.

6. be arranged simultaneously zeroing hole (culture medium, CCK8), control wells (cell, culture solution, CCK8) and test hole (cell, Drug solution, culture solution, CCK8).

7. preparing the Chinese medicine (freeze-dried powder prepared by embodiment 1) of saturated concentration with ultrapure water, culture medium is then used (RPMl-1640 culture medium) is diluted to the different qualities concentration such as 1%, 1.5%, 2%, 2.5%, 3% for cell culture, uses CCK8 method analyzes cell activity, and control cell relative activity is set as 100%.Drug concentration required for cell activity drop by half For half lethal dose (IC50).Experiment is independent in triplicate, and data are average value ± SE.

1.2 experimental result

As a result as shown in Fig. 2, with drug concentration increase, cell activity is gradually reduced.Chinese medicine is in vitro culture The half lethal dose (LC50) of human A549 cell lines is 2.6 ± 0.3%.

Embodiment 4: therapeutic effect of the Chinese medicine composition to the primary lung cancer of mouse

2.1 experimental method

In-vivo tumour therapeutic effect is ruled by law using intragastric administration on mice treats primary carcinoma measurement primary carcinoma quantity and size to realize.Tool Gymnastics is made as follows:

1, it is injected intraperitoneally using urethane and induces the primary lung cancer of kunming mice, lung cancer induction rate 100%, pathological analysis determines For gland cancer.Before stomach-filling, mouse is grouped at random, every group of 5 mouse.

2, Chinese medicine paste is prepared with ultrapure water, according to 1g/kg weight (freeze-dried powder prepared by embodiment 1), 200 μ L/ times, often It is primary, and continuous medicine-filling 14 days.Control mice is pasted using ultrapure water instead of Chinese medicine, same stomach-filling, 200 μ L/ times, and daily one It is secondary, continuous medicine-filling 14 days.

3, after being administered 14 days, eye socket takes blood to put to death mouse, and solution takes full lung, takes pictures, and counts Lung neoplasm quantity, takes Lung neoplasm It is fixed to carry out pathological analysis.

2.2 experimental result

As shown in figure 3, for the Lung neoplasm size of Chinese medicine group mouse significantly less than control, effect range estimation is visible after stomach-filling 14 days. Lung neoplasm quantity, which is considerably less than, to be compareed, 5 mouse of control group totally 27 tubercles (6,6,4,3,8), Chinese medicine group only 7 tubercles (2, 1、1、2、1)。

Pathological analysis is the results show that tubercle is adenocarcinoma of lung (such as Fig. 4).

Embodiment 5: adjustment effect of the Chinese medicine to mouse immune system.

3.1 experimental method

1, it is injected intraperitoneally using urethane and induces the primary lung cancer of kunming mice, mouse is grouped at random, every group of 9 mouse.

2, Chinese medicine paste is prepared with ultrapure water, according to 1g/kg weight (freeze-dried powder prepared by embodiment 2), 200 μ L/ times, often It is primary, and continuous medicine-filling 14 days.Control mice is pasted using ultrapure water instead of Chinese medicine, same stomach-filling, 200 μ L/ times, and daily one It is secondary, continuous medicine-filling 14 days.

3, after being administered 14 days, eye socket takes blood mouse to put to death mouse, and solution takes spleen, is homogenized, and 22 μm of membrane filtrations take slender Born of the same parents' suspension as a child with the CD4 antibody incubation 1 of fluorescent marker carries out flow cytometry, detects CD4 positive cell content.

3.2 experimental result

As shown in Figure 5, after Chinese medicine stomach-filling processing, spleen CD4 positive cell ratio is obviously increased, and deposits compared with the control group In significant difference (P < 0.05).

The foregoing is merely the preferred embodiments for doing invention, all in spirit and original of the invention not to limit invention Within then, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.

Claims

1. a kind of pharmaceutical composition for treating lung cancer, the composition are made of the following Chinese medicine material of quality proportioning: naze 30 ~40 parts, 20~30 parts of stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, 5~15 parts of American Ginseng, 20~40 parts of Radix Astragali, 5~15 parts of Schisandra chinensis, 15~35 parts of ramulus cinnamomi, 5~10 parts of gun additioner, 10~20 parts of Semen Cuscutae, 10~20 parts of the fruit of glossy privet, 1~6 part of pilose antler, 10~20 parts of HERBA EPIMEDII, the root of straight ladybell 10 ~20 parts, 10~20 parts of Radix Ophiopogonis, 20~40 parts of oldenlandia diffusa, 10~20 parts of the root bark of white mulberry, 10~20 parts of Radix Rehmanniae, Prunella vulgaris 20~ 40 parts, 10~20 parts of Radix Salviae Miltiorrhizae, 10~20 parts of radix paeoniae rubra, 5~15 parts of Fructus Aurantii, 5~15 parts of Radix Curcumae, 20~40 parts of black nightshade, edible tulip 10 ~20 parts, 20~40 parts of Sculellaria barbata, 5~15 parts of lily, 5~15 parts of peach kernel.

2. pharmaceutical composition as described in claim 1, it is characterised in that the composition material quality composition is as follows: naze 35 Part, 25 parts of stir-baked CARAPAX TRIONGCIS with sand then treated with vinegar, 10 parts of American Ginseng, 30 parts of Radix Astragali, 9 parts of Schisandra chinensis, 20 parts of ramulus cinnamomi, 6 parts of gun additioner, 15 parts of Semen Cuscutae, female Loyal son 15 parts, 3 parts of pilose antler, 15 parts of HERBA EPIMEDII, 15 parts of the root of straight ladybell, 15 parts of Radix Ophiopogonis, 30 parts of oldenlandia diffusa, 15 parts of the root bark of white mulberry, Radix Rehmanniae 15 parts, 30 parts of Prunella vulgaris, 15 parts of Radix Salviae Miltiorrhizae, 15 parts of radix paeoniae rubra, 10 parts of Fructus Aurantii, 10 parts of Radix Curcumae, 30 parts of black nightshade, 15 parts, half of edible tulip 30 parts of lotus, 10 parts of lily, 10 parts of peach kernel.

3. application of the pharmaceutical composition of any of claims 1 or 2 in the drug of preparation treatment lung cancer.

4. application as claimed in claim 3, it is characterised in that the lung cancer is adenocarcinoma of lung.