CN101152510A

CN101152510A - Pharmaceutical composition, preparing method and use the same

Info

Publication number: CN101152510A
Application number: CNA2007101216361A
Authority: CN
Inventors: 王�锋
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-09-12
Filing date: 2007-09-12
Publication date: 2008-04-02

Abstract

The invention discloses a medicine composition with anti-tumor and immune functions and a method of preparing the composition, a quality control method and the functions of the composition. The composition comprises artificial ox gallstone, honeysuckle flower, scolopendra, pangolin scale, toad venom, dandelion and other 18 traditional Chinese medicines; during preparation, the medicine composition fully displays the effective medicine by decocting, filtering, condensing, etc. different components; meanwhile, the invention also provides the quality control method of identifying the components and determining the content for the composition; the medicine composition of the invention has the effects of heat-toxin clearing, detumescence and removing blood stasis, strengthening body resistance, etc.; in addition, a plurality of tests prove that the medicine composition of the invention has anti-cancer and suppress cancer functions and is in particular applicable to the patients suffering from advanced gastrointestinal tract tumor; the medicine composition is free of toxicity, safety and reliable, can solve the side effect to the gastrointestinal tract brought by chemotherapy, can protect the hemogram and the immune function, has in particular obvious therapeutic effect to the patients suffering from stasis, and can become a novel anti-tumor Chinese traditional patent medicine.

Description

A kind of pharmaceutical composition and its production and use

Technical field

The present invention relates to a kind of pharmaceutical composition and preparation method thereof, method of quality control and purposes, particularly a kind of have antitumor and regulate pharmaceutical composition of immunologic function and preparation method thereof, method of quality control and purposes.

Background technology

Tumor is normal cell that growing in the human body or sophisticated, under various carcinogenic factor effects, the change that oncogene and antioncogene take place---comprises the activation of oncogene, the disappearance and the sudden change of antioncogene---and influences the phenotype and feature, be converted into and form behind cancerous cell biology of cell.It is different that tumor cell and Normocellular structure, function and metabolism etc. exist, and they can not be by the growth of normal metabolic rule, and unfettered and control is irregular ramp, can destroy the structure of normal structure organ and influence its normal function.Malignant tumor is that current serious influences human health, threatens one of principal disease of human life.Tumor patient causes body constitution to descend in therapeutic process, and it is very fragile that immune system becomes.Add some remaining tumor cell long-term existence in human body, in case patient's immunologic function degression, it just may be revived, and a large amount of breedings, make and have a relapse, cancer constitutes world today's All Countries three big causes of death with cardiovascular and cerebrovascular disease and contingency.Current, people have had clearer and more definite understanding for immunity of organism in the tumor development process, and corresponding basis and clinical research have been carried out, the means of treatment are also more and more, but nowadays many medicines and other treatment meanss as chemotherapy, all cause very big infringement to patient's hemogram and darling renal function, even some medicine also can produce toxic and side effects, threatens patient's life.Therefore, World Health Organization (WHO) and hygiene department of national governments all classify capture cancer as a top priority as.

Summary of the invention

The present invention seeks to be achieved through the following technical solutions:

The raw material of pharmaceutical composition of the present invention consists of:

Artificial Calculus Bovis 0.1-1 weight portion Flos Lonicerae 20-50 weight portion Scolopendra 0.5-2 weight portion

Squama Manis 10-30 weight portion Venenum Bufonis 1-5 weight portion Herba Taraxaci 30-80 weight portion

Herba Scutellariae Barbatae 5-10 weight portion Pseudobulbus Cremastrae Seu Pleiones 10-30 weight portion Rhizoma Curcumae 10-30 weight portion

Herba Hedyotidis Diffusae 20-50 weight portion Radix Sophorae Flavescentis 30-70 weight portion Herba Solani Nigri 10-50 weight portion

Margarita 0.1-0.5 weight portion Radix Et Rhizoma Rhei 10-30 weight portion Rhizoma Dioscoreae Bulbiferae 3-9 weight portion

Olibanum 1-5 weight portion Myrrha 1-5 weight portion Rhizoma Corydalis 10-40 weight portion

Flos Carthami 1-7 weight portion Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens) 20-50 weight portion Radix Codonopsis 30-70 weight portion

Radix Astragali 40-90 weight portion Radix Et Caulis Acanthopanacis Senticosi 30-80 weight portion Fructus Amomi 5-20 weight portion.

The crude drug composition and the proportion optimization of pharmaceutical composition of the present invention are as follows:

Artificial Calculus Bovis 0.6 weight portion Flos Lonicerae 38 weight portion Scolopendras 1 weight portion

Squama Manis 18 weight portion Venenum Bufoniss 2.5 weight portion Herba Taraxacis 56 weight portions

Herba Scutellariae Barbatae 8 weight portion Pseudobulbus Cremastrae Seu Pleioness 18 weight portion Rhizoma Curcumae 18 weight portions

Herba Hedyotidis Diffusae 38 weight portion Radix Sophorae Flavescentiss 48 weight portion Herba Solani Nigris 30 weight portions

Margarita 0.3 weight portion Radix Et Rhizoma Rhei 18 weight portion Rhizoma Dioscoreae Bulbiferaes 6 weight portions

Olibanum 3 weight portion Myrrhas 3 weight portion Rhizoma Corydalis 28 weight portions

Flos Carthami 4 weight portion Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens)s 38 weight portion Radix Codonopsis 54 weight portions

The Radix Astragali 66 weight portion Radix Et Caulis Acanthopanacis Senticosis 56 weight portion Fructus Amomis 12 weight portions.

Artificial Calculus Bovis 0.9 weight portion Flos Lonicerae 21 weight portion Scolopendras 0.6 weight portion

Squama Manis 28 weight portion Venenum Bufoniss 4.5 weight portion Herba Taraxacis 32 weight portions

Herba Scutellariae Barbatae 6 weight portion Pseudobulbus Cremastrae Seu Pleioness 28 weight portion Rhizoma Curcumae 28 weight portions

Herba Hedyotidis Diffusae 21 weight portion Radix Sophorae Flavescentiss 31 weight portion Herba Solani Nigris 48 weight portions

Margarita 0.4 weight portion Radix Et Rhizoma Rhei 12 weight portion Rhizoma Dioscoreae Bulbiferaes 4 weight portions

Olibanum 4 weight portion Myrrhas 4 weight portion Rhizoma Corydalis 12 weight portions

Flos Carthami 2 weight portion Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens)s 48 weight portion Radix Codonopsis 68 weight portions

The Radix Astragali 42 weight portion Radix Et Caulis Acanthopanacis Senticosis 32 weight portion Fructus Amomis 18 weight portions.

Artificial Calculus Bovis 0.2 weight portion Flos Lonicerae 48 weight portion Scolopendras 1.8 weight portions

Squama Manis 12 weight portion Venenum Bufoniss 1.5 weight portion Herba Taraxacis 76 weight portions

Herba Scutellariae Barbatae 14 weight portion Pseudobulbus Cremastrae Seu Pleioness 12 weight portion Rhizoma Curcumae 12 weight portions

Herba Hedyotidis Diffusae 48 weight portion Radix Sophorae Flavescentiss 68 weight portion Herba Solani Nigris 12 weight portions

Margarita 0.2 weight portion Radix Et Rhizoma Rhei 28 weight portion Rhizoma Dioscoreae Bulbiferaes 8 weight portions

Olibanum 2 weight portion Myrrhas 2 weight portion Rhizoma Corydalis 38 weight portions

Flos Carthami 6 weight portion Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens)s 22 weight portion Radix Codonopsis 32 weight portions

The Radix Astragali 88 weight portion Radix Et Caulis Acanthopanacis Senticosis 78 weight portion Fructus Amomis 6 weight portions.

Pharmaceutical composition of the present invention can adopt the conventional method of galenic pharmacy to add conventional adjuvant and make and be applicable to clinical multiple dosage form: capsule, powder, tablet, granule, pill or oral liquid.

Preparation of drug combination technology of the present invention can also be:

Get crude drug, earlier Flos Lonicerae, Herba Taraxaci, Herba Scutellariae Barbatae, Herba Hedyotidis Diffusae, Radix Sophorae Flavescentis, Herba Solani Nigri, Rhizoma Dioscoreae Bulbiferae, the Radix Astragali and Radix Et Caulis Acanthopanacis Senticosi are decocted with water three times, 1-3 hour for the first time, 0.5-2 hour for the second time, 0.5-1.5 hour for the third time, collecting decoction filters, and it is 1.00～1.50 clear paste that filtrate decompression is condensed into 50-90 ℃ of following relative density; Olibanum, Myrrha heating are dissolved, filter, filtrate merges, and adds in the above-mentioned clear paste; Artificial Calculus Bovis, Margarita are ground into impalpable powder; All the other Scolopendras etc. are ground into fine powder, with above-mentioned impalpable powder mixing, add in the clear paste, stir, and drying is ground into fine powder, and mixing adds conventional adjuvant and makes capsule, powder, tablet, granule, pill, oral liquid.

Get crude drug, earlier Flos Lonicerae, Herba Taraxaci, Herba Scutellariae Barbatae, Herba Hedyotidis Diffusae, Radix Sophorae Flavescentis, Herba Solani Nigri, Rhizoma Dioscoreae Bulbiferae, the Radix Astragali and Radix Et Caulis Acanthopanacis Senticosi are decocted with water three times, 2 hours for the first time, 1.5 hours for the second time, 1 hour for the third time, collecting decoction filters, and it is 1.20～1.25 clear paste that filtrate decompression is condensed into 75 ℃ of following relative densities; Olibanum, Myrrha heating are dissolved, filter, filtrate merges, and adds in the above-mentioned clear paste; Artificial Calculus Bovis, Margarita are ground into impalpable powder; All the other Scolopendras etc. are ground into fine powder, with above-mentioned impalpable powder mixing, add in the clear paste, stir, and drying is ground into fine powder, and mixing adds conventional adjuvant and makes capsule, powder, tablet, granule, pill, oral liquid.

The method of quality control of medicament composition capsule of the present invention comprises one or more in following discriminating or the assay:

Differentiate:

A. get medicament composition capsule content of the present invention, put microscopically and observe: the pollen grain similar round, short thorn of diameter 30-80 μ m outer wall tool and point-like carving stricture of vagina have 3 germinal aperatures; Endotesta stone cell brownish red, the class polygon is seen on the surface, and wall thickness, cell contain siliceous; Unsetting fragment is near colourless or faint yellow, and similar round not of uniform size, ellipse or irregular shape cavity are arranged mostly; Calcium oxalate cluster crystal is big, diameter 40-160 μ m; Sclerenchyma fragment green-yellow, cell class polygon or slightly prolongation, wall is crooked slightly, and the beaded that has thickens, and pit is fine and closely woven; Connect latex dust, diameter 10-20 μ m contains fine particle shape thing; Irregular fragment is translucent, and is glossy, and the surface shows graininess, the visible fine texture that has;

B. get medicament composition capsule content 2-6g of the present invention, add methanol 10-30ml, flooded 5-15 minute, filter, get filtrate 5-15ml, evaporate to dryness, residue adds water 5-15ml makes dissolving, adds hydrochloric acid 1ml again, puts in the water-bath reflux 20-40 minute, cooling immediately, divide 2 extractions with ether 10-30ml, merge ether extracted liquid, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 2-7 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 20-80 ℃ of petroleum ether-Ethyl formate-formic acid=10-20: 3-8: 1 upper solution is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes redness;

C. get medicament composition capsule content 2-7g of the present invention, add strong ammonia solution 1ml and chloroform 10-30ml, flooded 1 hour, jolting constantly filters, and filtrate evaporate to dryness, residue add ethanol 2-7ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10-30 μ 1, reference substance solution 1 μ l, put respectively on same silica gel g thin-layer plate, with normal hexane-chloroform-methanol=5-15: 3-9: 1 is developing solvent, launch, take out, dry, after putting in the iodine vapor the smoked several seconds, put under the 365nm ultraviolet light and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

D. get medicament composition capsule content 1-5g of the present invention, add chloroform 15-50ml, reflux, extract, 3-7 hour, filter, add active carbon 0.1-0.5g in the filtrate, jolting was placed 15-45 minute, filtered, filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 1-3mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 5-15 μ l, reference substance solution 1-3 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=2-6: 2-4: 2-4 is developing solvent, launches, and takes out, dry, spray, is put under the 365nm ultraviolet light and is inspected 90-120 ℃ of baking 2-6 minute with the 5-15% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle;

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=10-30: 10-30: 50-90: 0.1; The detection wavelength is 220nm; Number of theoretical plate calculates by the matrine peak should be not less than 8000; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 5-15mg of phosphorus pentoxide drying under reduced pressure to constant weight, put in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 1-5ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, that is, every 1ml contains matrine 40-80 μ g; The preparation of need testing solution: get the medicament composition capsule content of the present invention under the content uniformity item, grind well, get 0.2-0.8g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 1-3ml and make moistening, add chloroform 10-40ml again, supersound process 10-30 minute, filter, residue and container, filter wash 2-6 time with chloroform, each 3-7ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 5-15 μ l of need testing solution of drawing injects chromatograph of liquid, measures, promptly; Every capsules content contains Radix Sophorae Flavescentis in matrine C 15H 24N 20, must not be less than 0.16mg.

The method of quality control of pharmaceutical composition of the present invention comprises one or more in following discriminating or the assay:

Differentiate:

A. get medicament composition capsule content of the present invention, put microscopically and observe: the pollen grain similar round, short thorn of diameter 43 ~ 66 μ m outer wall tools and point-like carving stricture of vagina have 3 germinal aperatures; Endotesta stone cell brownish red, the class polygon is seen on the surface, and wall thickness, cell contain siliceous; Unsetting fragment is near colourless or faint yellow, and similar round not of uniform size, ellipse or irregular shape cavity are arranged mostly; Calcium oxalate cluster crystal is big, diameter 60 ~ 140 μ m; Sclerenchyma fragment green-yellow, cell class polygon or slightly prolongation, wall is crooked slightly, and the beaded that has thickens, and pit is fine and closely woven; Connect latex dust, diameter 12 ~ 15 μ m contain fine particle shape thing; Irregular fragment is translucent, and is glossy, and the surface shows graininess, the visible fine texture that has;

B. get medicament composition capsule content 4g of the present invention, add methanol 20ml, flooded 10 minutes, filter, get filtrate 10ml, evaporate to dryness, residue adds water 10ml makes dissolving, adds hydrochloric acid 1ml again, puts in the water-bath reflux 30 minutes, cooling immediately, divide 2 extractions with ether 20ml, merge ether extracted liquid, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, upper solution with 30 ~ 60 ℃ of petroleum ether-Ethyl formate-formic acid=15: 5: 1 is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes redness;

C. get medicament composition capsule content 5g of the present invention, add strong ammonia solution 1ml and chloroform 20ml, flooded 1 hour, jolting constantly filters, and filtrate evaporate to dryness, residue add ethanol 5ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 20 μ l, reference substance solution 1 μ l, put respectively on same silica gel g thin-layer plate, with normal hexane-chloroform-methanol=10: 6: 1 was developing solvent, launched, and took out, dry, put in the iodine vapor the smoked several seconds after, put under the 365nm ultraviolet light and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

D. get medicament composition capsule content 3g of the present invention, add chloroform 25ml, reflux, extract, 5 hours filters, and adds active carbon 0.3g in the filtrate, and jolting was placed 30 minutes, filtered, and filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 2 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=4: 3: 3 was developing solvent, launched, and took out, dry, spray, is put under the 365nm ultraviolet light and is inspected 105 ℃ of bakings 3-4 minute with 10% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle;

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=18: 18: 70: 0.1; Detecting wavelength is that the 220nm number of theoretical plate should be not less than 8000 by the calculating of matrine peak; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 10mg of phosphorus pentoxide drying under reduced pressure to constant weight, puts in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 3ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Every 1ml contains matrine 60 μ g; The preparation of need testing solution: get the medicament composition capsule content of the present invention under the content uniformity item, grind well, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 2ml and make moistening, add chloroform 25ml again, supersound process 20 minutes filters, and residue and container, filter wash 4 times with chloroform, each 5ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; Every capsules content contains Radix Sophorae Flavescentis in matrine C 15H 24N 20, must not be less than 0.16mg.

The above-mentioned Olibanum of the present invention, Myrrha and Rhizoma Corydalis can use Olibanum (processed), Myrrha (processed) and Rhizoma Corydalis (processed) to replace; Squama Manis is for concocting Squama Manis.

Pharmaceutical composition of the present invention has effects such as heat-clearing and toxic substances removing, detumescence blood stasis dispelling, the body resistance strengthening and constitution consolidating, show that by a large amount of experiments pharmaceutical composition of the present invention not only can improve normal mouse peritoneal macrophage phagocytic function, and the macrophage phagocytic function of hydrocortisone inhibition back mice and tumor-bearing mice is all had remarkable potentiation; The electron microscopic observation result shows that also pharmaceutical composition of the present invention has immunologic function that strengthens the cancer patient and the effect that suppresses tumor growth; And find further that by clinical observation on the therapeutic effect pharmaceutical composition of the present invention has anticancer and cancer suppressing action; be particularly useful for the Infusion in Patients with Digestive in late period; its avirulence; safe and reliable; can overcome the digestive tract side reaction that chemotherapy is brought; hemogram and immunologic function are had protective effect, and particularly evident for blood stasis syndrome patient curative effect, it can become a kind of new antineoplastic Chinese traditional medicine.

Following experimental example and embodiment are used to further specify but are not limited to the present invention.

The electron microscopic observation experiment of experimental example 1 medicine composite for curing pulmonary carcinoma of the present invention, esophageal carcinoma and gastric cancer

With Electronic Speculum 33 routine cancer patients' biopsy material has been done observation, pulmonary carcinoma 15 examples wherein, the esophageal carcinoma 12 examples, gastric cancer 6 examples; Comprise treatment and organize 17 examples, matched group 16 examples; Biopsy material is taked by the surgery medical personnel, put into immediately and fix before 3% glutaraldehyde is done, sending Electron Microscopy Room to carry out the back with Osmic acid. fixes, after buffer is cleaned, with the embedding of Epon312 epoxy resin, 60 ℃ of polymerizations 48 hours, on the LKB ultramicrotome, cut into slices with diamant, uranium acetate and lead citrate are two to be dyed, and puts under the transmission electron microscope and observes, and the result is reported as follows:

With pulmonary carcinoma is example: the adenocarcinoma cell of matched group, and circumference is clear, and nucleus is irregular, perinuclear space broadening, nucleopore is obvious; Around heterochromatin mainly was published in, euchromatin was many in nuclear central authorities, and kernel is remarkable; Abundant smooth surfaced endoplasmic reticulum (smoothendplasmic retiula) is arranged in the Cytoplasm, because of producing a large amount of mucus, it forms many mucocysts (mucousvesi-cles), mitochondrion (mitochondria) often is extruded into arc or irregularly shaped by mucocyst, is also shown in lysosome (lysosomes) (Fig. 1); Many mucocysts merge mutually, often can form sheet " mucus lake " (mucouslake), and cell volume increases, and nucleus is just as ait, and are extruded into polygon by mucus, and mitochondrion is sandwiched in (Fig. 2) between the mucus lake more; These show matched group lung adenocarcinoma cell well differentiated, and synthetic mucus function is active, and the cell growth is normal; The squamous cell carcinoma of matched group, alignment for the boundary line confusion, iuntercellular connects with desmosome (desmosome), and the microvillus (microvilli) that protrudes in cell surface is arranged; Cytoplasm contains more micro-filament (tonofibrils) and glycogen granule (glucogen partivls); Mitochondrion has the different vacuolar degeneration of degree; Nucleus is rich in euchromatin, and kernel is obvious, and nuclear membrane is clear, perinuclear space normal (Fig. 3); The squamous cell carcinoma that has can have 2-3 kernel, and volume is big, often is netted shape, is full of euchromatin in the nuclear, heterochromatin seldom, perinuclear space broadening, nucleopore is obvious, whole cancerous cell nucleocytoplasmic ratio significantly lack of proper care (Fig. 4); These show the squamous cell carcinoma well differentiated, and it is normal substantially to grow; In general,,, do not observe large stretch of cancer cellular necrosis, do not see tangible immunocyte infiltration phenomenon yet as mitochondrion vacuolation and the many nuclear inactive states of heterochromatin though the matched group cancerous cell can be seen some reversibility regressions.

The lung adenocarcinoma cell of treatment group often can be seen neutrophilic granulocyte and lymphocytic infiltration on every side, and the neutrophilic granulocyte of infiltration contacts closely with cancerous cell, the fuzzy or appearance (Fig. 5) that disappears of both cell membrane boundaries; The lung adenocarcinoma cell disintegrate that has, mucocyst and organelle loose from, the bare nucleus of shape free state, the bare nucleus that has also break (Fig. 6); The bare nucleus that has is then by a large amount of collagen fiber embeddings (Fig. 7); Be also shown in the cancerous cell (Fig. 8) of necrosis in blocks; The Lung Squamous Carcinoma Cells of treatment group has lymphocyte and neutrophil infiltration on every side; The lymphocyte that soaks into contacts (Fig. 9) closely with cancerous cell; In the cancerous cell of disintegrate in flakes, be also shown in many discrete organelles or cell debris (Figure 10); The lymphocyte that has immerses in the cancer nests, directly injects (Figure 11) between the cancerous cell; Be also shown in the cancerous cell of necrosis in blocks, the most of dissolving of cell membrane disappears, the organelle vacuolation, and nucleus distortion pyknosis, internal structure is fiber-like and changes (Figure 12); In general, treatment group lung carcinoma cell is downright bad serious, and has tangible immunocyte to soak into.

The esophageal carcinoma of treatment group is similar to the observed result of pulmonary carcinoma.

Conclusion:

Can see cancer cellular necrosis in blocks in the treatment group, in matched group, then not observe this kind phenomenon, can consider the therapeutical effect of medicine; As usual seeing that in the comparison of treatment group leukocyte infiltration and lymphocyte immerse cancer nests, and contact closely with cancerous cell, is not fortuitous phenomena; These show that the treatment group has stronger organism immune response.Neutrophil infiltration belongs to nonspecific immune reaction or inflammatory reaction, mainly shows as phagocytosis, removes foreign body; But the lysosomal enzyme that discharges after the neutrophilic granulocyte disintegrate also causes the infringement of cancerous cell; The close contact of lymphocyte (T) and cancerous cell is essential condition, and the lymphokine that the lymphocyte that is activated is emitted is one of reason that causes cancerous cell infringement, have specific antibody in the presence of, lymphocyte (B) can produce infringement to cancerous cell.The electron microscopic observation result shows that pharmaceutical composition of the present invention has the effect of the immunologic function tumor growth that strengthens the cancer patient.

2 pharmaceutical composition antitumor actions of experimental example and to Immune Effects

One, experiment material

Animal: select 18-24g Kunming kind healthy mice for use, 615 and the C57 mouse inbred lines, male female dual-purpose;

Tumor strain: mice S180, P388, ECA, L615 and LEWIS pulmonary carcinoma;

Medicine: medicament composition capsule content of the present invention, provide powder by producer, be made into suspension; Cyclophosphamide 200mg/ props up, Shanghai No.12 Pharmaceutical Factory; Ametycin 2mg/ props up, Japanese Kyowa Hakkokogyo Co., Ltd; Hydrocortisone 25mg/5ml, Tianjin people pharmaceutical factory.

Two, experimental technique

1, anti-tumor experiment: conventional inoculated tumour, treatment, prevention and the drug combination effect of observing pharmaceutical composition antitumor activity of the present invention respectively by national anticancer cooperation meeting regulation, are calculated its tumor control rate and increase in life span;

2, immune function experiment:

1. immune organ weight is measured: measure pharmaceutical composition of the present invention respectively to normal mouse, tumor-bearing mice be subjected to cyclophosphamide to suppress the weight of back mouse thymus and spleen;

2. macrophage phagocytic function is measured: measure pharmaceutical composition of the present invention respectively to normal mouse be subjected to hydrocortisone to suppress back Turnover of Mouse Peritoneal Macrophages phagocytic activity;

3. HC50 measures: carry out according to the hemolysin algoscopy of Xu Xueying report substantially.

Three, experimental result

1, antitumor action

(1) to the therapeutic effect of mice transplanted tumor: behind the inoculated tumour, next day random packet, 10 every group, oral administration, solid tumor group administration 10 days, ehrlich ascites carcinoma group administration 7 days, matched group is given the isometric(al) solvent, obtains tumor control rate and increase in life span in accordance with regulations, sees Table 1, table 2:

Table 1 pharmaceutical composition of the present invention is to the therapeutic effect of mouse transplanting tumor

* be the ip administration;

Table 2 pharmaceutical composition of the present invention is to the therapeutic effect of mouse transplanting tumor

* be the ip administration;

Giving the dosage of 1.5g/kg/ day, is 63.41% to the suppression ratio of S180, is 87.24% to ECA animal life rate elongation, the active degree of animal also than matched group for well; Show that pharmaceutical composition of the present invention has the obvious treatment effect to mice transplanted tumor.

(2) to the mouse transplanting tumor preventive effect: before the animal inoculation tumor, played the continuous oral administration respectively in 7,14 and 21 days with the dosage of pharmaceutical composition 1.5g/Kg/ day of the present invention, 0,75g/Kg/ day, once a day, in drug withdrawal conventional inoculation next day, solid tumor inoculation back was cutd open and is got the tumor piece on the 11st day, obtained kind of a tumor suppression ratio; Ascites tumor and the leukemia accumulative total natural law of surviving from the inoculation calculates increase in life span, sees Table 3, table 4:

Table 3 pharmaceutical composition of the present invention is to the preventive effect of mice transplanted tumor

Table 4 pharmaceutical composition of the present invention is to the preventive effect of mice transplanted tumor

The result shows: pharmaceutical composition of the present invention all has remarkable preventive effect to mice transplanted tumor, and S180 and P388 inhibition effect are increased with dosage, has dose dependent, and is close with its therapeutical effect.

(3) anticancer therapeutic that share with MMC: give the MMC of ip in mice 1.0mg/Kg/ day, observe its tumor killing effect, the results are shown in Table 5, table 6:

The anticancer therapeutic that table 5 pharmaceutical composition of the present invention and MMC share

The anticancer therapeutic that table 6 pharmaceutical composition of the present invention and MMC share

Experiment shows: drug combination is 70.25% to the suppression ratio of S180, than using MMC to improve 38% separately, increase in life span to the ECA animal is 223.68%, than using MMC to improve 4.5 times separately, in experiment in two months, small dose group has 60% animals survived, and matched group is all dead in 18 days.

2, immunization

(1) to mouse immune organ weight's influence

Influence to normal mouse immune organ weight: select the 18-22g Kunming mouse for use, random packet, the difference oral administration, continuous 7 days, next day is put to death animal in drug withdrawal, cuts open to get thymus and spleen is weighed, and gauge index, see Table 7, visible pharmaceutical composition of the present invention can obviously increase mouse spleen and thymic weight;

To using cyclophosphamide mouse immune organ weight's influence: administration rose by the continuous ip cyclophosphamide of 75mg/kg dosage (CTX) 3 days on the 1st day, following steps are the same, see Table 8, as seen pharmaceutical composition of the present invention can obviously resist the immunosuppressive action of cyclophosphamide, and animal immune the organ weight significantly go up.

Table 7 couple normal mouse immune organ weight's influence

Table 8 couple application cyclophosphamide mouse immune organ weight's influence

Influence to the tumor-bearing mice immune organ weight: conventional inoculation S180, next day, random packet and successive administration were 7 days, and following steps are the same, see Table 9, as seen pharmaceutical composition of the present invention can significantly increase lotus tumor immune organ weight, even doubles many than the spleen escheat of normal control treated animal.

The influence of table 9 pair tumor-bearing mice immune organ weight

(2) to the influence of Turnover of Mouse Peritoneal Macrophages phagocytic function

Influence to normal macrophage phagocytosis of mice: 30 of mices, be divided into three groups at random, press 0.75g/kg, 1.5g/kg dosage medicinal-composition suspension liquid of the present invention respectively, oral administration medicine supplying 7 days, matched group is given the isometric(al) solvent; Drug withdrawal every ip in mice on the same day 5% chicken red blood cell NS suspension 0.2ml, put to death animal after 24 hours, every animal is all used 2.5ml Hank ' S liquid flushing abdominal cavity, drips the 0.2ml flushing liquor on microscope slide, 37 ℃ of temperature were incubated 30 minutes, washed away with NS and dripped not adherent cell on the sheet; Methanol is fixed, the dyeing of Ji's nurse Sa Wright's stain, and oily mirror is observed macrophage phagocytic CRBC number down, calculates its phagocytic rate, the results are shown in Figure 13.

To being subjected to the influence of the macrophage phagocytosis of mice that hydrocortisone suppresses: test the same substantially, only in administration simultaneously administration group and matched group all by 5mg/kg dosage ip hydrocortisone 2 days, and be provided with the normal control group, and do not inject hydrocortisone, the results are shown in Figure 13.

Influence to the tumor-bearing mice phagocytic function: select 40 of C57 mouse inbred liness for use, wherein inoculated Lewis lung cancer in 30 days routinely, be divided into three groups next day at random, 10 is the normal control group in addition, and following steps are the same, the results are shown in accompanying drawing 13.

The result shows that pharmaceutical composition of the present invention not only can improve normal mouse peritoneal macrophage phagocytic function, and the macrophage phagocytic function of hydrocortisone inhibition back mice and tumor-bearing mice is all had remarkable potentiation.

(3) influence that the mice serum hemolysin is formed

Select 615 mouse inbred liness for use, male and female half and half, by preceding method grouping and administration, method adopts the hemolysin algoscopy; Every Mus is accepted sheep red blood cell (SRBC) (SRBC) 0.2mlip immunity simultaneously after the drug withdrawal, and posterior orbit was got blood on 4th, separation of serum; After serum dilutes by 1: 50 with NS, get 1ml, add 0.5mlSRBC and 1ml complement (1: 10 dilution guinea pig serum), temperature was incubated 10 minutes, centrifugal behind the ice bath, get supernatant 1ml, add 3ml Dou Shi liquid, in the trap value of 540nm place working sample, make the trap value of blank and SRBC HD50 simultaneously, see Table 10, the HC50 of visible pharmaceutical composition 0.75g/kg dosage of the present invention shows that apparently higher than matched group obviously enhancing antibody forms.

The influence of table 10 pair mouse humoral immune (HC50)

Experimental results show that pharmaceutical composition of the present invention has the obvious treatment effect to mice transplanted tumor, to the solid tumor suppression ratio is 63.419%, the preventive administration of different time, and its preventive effect strengthens with dosage, share with chemotherapeutic, can significantly improve suppression ratio and prolong life cycle; Pharmaceutical composition of the present invention has tangible immune-enhancing effect, can obviously increase the animal immune organ weight, improve the peritoneal macrophage phagocytic function, promote hemolysin to form, this potentiation does not singly exist at animal normal physiological state, and after using immunosuppressant, obvious potentiation also being arranged, after the medication, the phagocytic function of animal recovers normal level; Pharmaceutical composition of the present invention can effectively improve the phagocytic function of body, is one of mechanism of its antitumor action.

Pharmaceutical composition toxicity of the present invention is low, and safety coefficient is big, and it is 5.38 0.87g/kg that karber's method records oral LD50, and poisoning mice is died from respiratory paralysis; Chronic toxicity test, various test ratings there is no obvious toxic and change.

Experimental example 3 pharmaceutical composition II phase clinical observation on the therapeutic effect of the present invention

One, physical data

1. case is originated:

This case derives from units such as Guang-amen Hospital, China Traditional Chinese Medicine Instl, Shanxi Province Tumor Hospital, Yangcheng, Shanxi Province tumour hospital, and each unit case is no less than 50 examples, sees Table 11:

Table 11 case distribution condition

	Gate of Pervasive Peace hospital	Shanxi Province Tumor Hospital	Yangcheng, Shanxi tumour hospital
	Gate of Pervasive Peace hospital	Shanxi Province Tumor Hospital	Yangcheng, Shanxi tumour hospital	The treatment group	199	52	51
Matched group	107	13	10	The treatment group	199	52	51
Matched group	107	13	10	Add up to	306	65	61

2. age situation:

Age is many between 40-70 year, maximum 87 years old age, and minimal ages 14 years old, wherein 50-60 year be maximum, accounts for 1/4,53.1 years old mean age, sees Table 12:

Table 12 age distribution situation

Grouping	n	＜40	41-50	51-60	61-70	＞70
Grouping	n	＜40	41-50	51-60	61-70	＞70	The treatment group	302	24	63	118	68	29
Matched group	130	13	36	43	26	12	The treatment group	302	24	63	118	68	29

3. sex situation:

In 432 examples male in the majority be 345 examples, women's 87 examples, men and women's ratio is 4: 1, but the treatment group is substantially parallel with matched group, sees Table 13:

Table 13 gender distribution condition

	The treatment group	Matched group	Add up to
	The treatment group	Matched group	Add up to	Grouping	n(％)	n(％)	n(％)
The male	237(68.70)	108(31.30)	345(79.86)	Grouping	n(％)	n(％)	n(％)
The male	237(68.70)	108(31.30)	345(79.86)	The women	67(74.71)	22(25.29)	87(20.14)

4. case, the sick kind reach by stages:

This observes case based on digestive tract tumor, gastric cancer ratio maximum, and secondly totally 148 examples are pulmonary carcinoma, have also observed the esophageal carcinoma and a small amount of other sick kind in addition, as breast carcinoma, intestinal cancer, cancer of pancreas, thyroid carcinoma, renal carcinoma etc.; All require with reference to " practical oncology " by stages, according to international TNM by stages standard carry out by stages, all patients require to be III, IV phase end-stage patients, two groups of cases in disease kind, pathology and by stages design in a basic balance, do not have obvious significant difference, see Table 14, table 15:

The sick kind of table 14 reaches by stages

The sick kind	The treatment group			Matched group			Add up to
	The treatment group			Matched group			Add up to	n	II	IV	n	III	IV	n
	Other total of stomach cancer and esophagus carcinoma pulmonary carcinoma	98 70 94 40 302	43 44 48 17 152	55 26 46 23 150	50 27 28 25 130	23 14 15 11 63	27 13 13 14 67	n	II	IV	n	III	IV	n	148 97 122 65 432

Table 15 pathology typing

	n	Treatment group (%)	Matched group (%)
	n	Treatment group (%)	Matched group (%)	Other total of scale cancer adenocarcinoma	169 239 24 432	130(82.28) 154(69.37) 18(81.82) 302	39(30.00) 85(65.38) 6(4.62) 130

5. case is selected regulations:

The patient who selects need possess following condition:

(1) pathology or cytology have clear and definite diagnosis;

(2) the band tumor existent of solid tumor is arranged;

(3) through the X line, inspection such as CT or body surface can be measured the focus size;

(4) the Ka Shi scoring can be finished III, the IV phase patients with terminal of the full course of treatment more than 60 minutes;

(5) though without any treatment or underwent operative, put, chemotherapy but fail to respond to any medical treatment or the recidivist, treatment this time needed and last course of treatment at interval more than one month;

(6) all require to be the inpatient;

(7) randomized is selected in the case grouping for use;

(8) this medicine therapist of voluntary accepting.

6. observed content:

(1) curative effect;

(2) doing well,improving situation;

(3) life quality.

(4) to the influence of hemopoietic, immunity, darling renal function;

(5) adverse effect.

Two, the administrated method and the course of treatment

This is observed case and is divided into two groups, treatment group 302 examples and matched group 130 examples; Matched group is divided into two groups again: TIANXIAN WAN group 30 examples (known Chinese medicine medicine for preventing) and chemotherapy group 100 examples (known anticancer Western medicine), and medicining condition is as follows:

1. treatment group: the adult obeys 9 medicament composition capsules of the present invention every day, and each 3, to take half an hour after meal every day 3 times, 6 weeks were a course of treatment;

2. according to group: the TIANXIAN WAN group: obey 9 every day, instructions about how to take medicine courses of treatment is with the treatment group;

Chemotherapy group: select according to the disease kind that " the corresponding chemotherapy regimen of Internal Medicine-Oncology handbook (1989 editions), 6 weeks were a course of treatment for use.

Three, experimental result

1. efficacy analysis

(1) efficacy analysis

According to " the criterion of therapeutical effect evaluation of Internal Medicine-Oncology handbook divides level Four, CR: alleviate PR fully: part is alleviated, S (NC): stable, and PD: progress; 432 routine patients of analysis and observation, stable 236 examples that add improvement account for 78.15% in the treatment group, and matched group 130 examples are 61.54%, and wherein the TIANXIAN WAN group accounts for 66.7%, and chemotherapy group accounts for 60.0%, and treatment group curative effect obviously is better than matched group, sees Table 16, table 17:

Table 16 total effects relatively

Grouping	n	PRn(％)	Sn(％)	PDn(％)	PR+Sn(％)	P
Grouping	n	PRn(％)	Sn(％)	PDn(％)	PR+Sn(％)	P	The treatment group	302	3(0.9)	233(77.15)	66(21.85)	236(78.15)	＜0.01
Matched group	130	8(3.40)	72(55.38)	50(38.5)	80(61.54)	＜0.01	The treatment group	302	3(0.9)	233(77.15)	66(21.85)	236(78.15)	＜0.01

Table 17 compares with different matched groups

Grouping	n	PRn(％)	Sn(％)	PDn(％)	PR+Sn(％)	P
Grouping	n	PRn(％)	Sn(％)	PDn(％)	PR+Sn(％)	P	Treatment group beauty organizes matched group	302 30 100	3(0.9) 8(8.00)	233(77.15) 20(66.67) 52(52.00)	66(21.85) 10(33.33) 40(40.00)	236(78.15) 20(66.67) 60(60.00)	＞0.05 ＜0.01

(2) the different sick efficacy analysis of planting

Three sick kinds have mainly been observed: gastric cancer, esophageal carcinoma, pulmonary carcinoma, it is 77.55% that the treatment group of gastric cancer is stablized improvement rate, the stable improvement rate 65% that obviously is better than matched group, the stable improvement rate of the esophageal carcinoma, pulmonary carcinoma also reaches 81.43% and 77.66%, to compare difference not obvious but with matched group 66.67% and 75.00%, other tumor also there is certain curative effect, sees Table 18, Figure 14:

The different sick curative effects of planting of table 18 compare

The sick kind	Grouping	n	PR	S	PD	PR+S(％)	P
The sick kind	Grouping	n	PR	S	PD	PR+S(％)	P	Gastric cancer esophageal carcinoma pulmonary carcinoma other	Treatment group treatment of control group group treatment of control group group treatment of control group group matched group	98 50 70 27 94 28 40 25	1 1 0 3 1 3 1 1	75 3l 57 15 72 18 29 9	22 17 13 9 21 7 10 15	76(77.55) 32(64.00) 57(81.43) 18(66.67) 73(77.66) 21(75.00) 30(75.00) 10(40.00)	＜0.05 ＞0.05 ＞0.05 ＜0.01

(3) curative effect of different traditional Chinese medical science typings relatively

Observing case is reference with the dialectical of " conventional treatment ", and due to illness kind and symptom are more, roughly return 8 classes, from typing, and qi-deficiency type, liver-stomach disharmony type, which kind of therapeutic effect is all relatively good; QI and blood any treatment thanks to two and type of deficiency of both QI and YIN is stablized improvement rate all＜70%, poor display; Resistance of the phlegm-damp stasis of blood and qi stagnation and blood stasis type, the matched group curative effect is bad, and treatment group curative effect is better, compares significant difference for two groups; This shows that this medicine more is applicable to the patient of blood stasis syndrome, see Table 19, Figure 15:

Table 19 Chinese medical discrimination and therapeutic effect relationship

Typing	The treatment group			Matched group
	The treatment group			Matched group			n	PR+S(％)	PD(％)	n	PR+S(％)	PD(％)
	Deficiency of vital energy deficiency of YIN deficiency of spleen-YANG deficiency of both QI and YIN phlegm-damp stasis of blood choke stagnates, and blood stasis incoordination between the liver and stomach QI and blood is two loses	45 35 18 40 32 36 57 39	42(93.33) 25(71.43) 16(88.89) 28(70.00) 23(71.88) 28(77.78) 50(87.72) 24(61.54)	3(6.67) 10(28.57) 2(11.11) 12(30.00) 9(28.12) 8(22.22) 7(12.28) 15(38.46)	18 13 7 14 20 17 21 20	16(88.89) 9(69.23) 6(85.71) 7(50.00) 6(30.00) 7(41.18) 18(85.71) 11(55.00)	n	PR+S(％)	PD(％)	n	PR+S(％)	PD(％)	2(11.11) 4(30.77) l(14.29) 7(50.OO) 14(70.00)* 6(58.82)* 304.29) 9(45.00)

*P＜0.050

2. doing well,improving situation:

From the symptom variation analysis, the weak condition improved of treatment group treatment rear section patient accounts for 28.8%, and pain relief accounts for 29.7%, compares significant difference with matched group, and is not obvious to other doing well,improving, sees Table 20, Figure 16:

Table 20 symptom variation analysis (1)

Grouping	The treatment group			Matched group
Grouping	The treatment group			Matched group			The weak pain cough poor appetite nausea and vomiting of breathing hard of symptom heating	(%) 25 (8.3) 87 (28.8) 41 (13.6) 88 (29.7) 18 (6.0) 54 (17.9) 10 (3.3) takes a turn for the better	Constant (%) 272 (90.0) 204 (68.6) * 253 (83.7) 203 (67.7) * 275 (91.0) 223 (73.8) 264 (87.4)	Increase the weight of (%) 5 (1.7) 11 (3.6) 8 (2.7) 11 (3.6) 9 (3.0) 25 (8.3) 28 (9.3)	(%) 4 (3.1) 6 (4.6) 1 (0.8) 16 (12.3) 5 (3.9) 9 (6.9) 8 (6.2) takes a turn for the better	Constant (%) 116 (89.2) 77 (59.2) 111 (85.4) 105 (76.9) 118 (90.8) 106 (81.5) 75 (57.7)	Increase the weight of (%) 10 (7.7) 47 (36.2) * 18 (13.8) 9 (6.9) 7 (5.4) 55 (42.3) * 47 (36.2) *

*P＜0.05

From treatment group and TIANXIAN WAN group symptom respectively more as can be seen: the treatment group makes moderate progress to pain, weak symptom, the TIANXIAN WAN group does not have obvious improvement to all kinds of symptoms, and chemotherapy group is except that making moderate progress to a small amount of patient's pain symptom, chemotherapy side effects such as that most of patient will produce is weak, nauseating, poor appetite see Table 21:

Table 21 different grouping symptom variation difference table (%)

	Symptom	Heating	Weak	Breathe hard	Pain	Cough	Poor appetite	Feel sick
	Symptom	Heating	Weak	Breathe hard	Pain	Cough	Poor appetite	Feel sick	Treatment group chemotherapy group TIANXIAN WAN	Alleviate to increase the weight of to alleviate to increase the weight of to alleviate and increase the weight of	6.62 3.00 10.00	25.17 36.00 16.67	10.92 11.00 67.20	25.5 10.00 10.00	0.33 2.00 0	6.29 40.0 19.33	5.96 41.0 6.67

3, body weight and life quality change:

(1) body weight: treatment back body weight change is not obvious as can be seen according to body weight situation of change before and after the treatment (＜1.5Kg is for rising, and＜1.5Kg is for descending), and TIANXIAN WAN group and chemotherapy group all have obvious decline, compare significant difference with the treatment group;

(2) (＜10 are divided into rising to life quality with the measurement of Karnofsky standards of grading,＜10 are divided into decline) treatment group in treatment back changes not obvious, many 7 examples that descend raise, and chemotherapy and TIANXIAN WAN group descender showed increased, be respectively 40% and 27%, compare variantly with treatment group (11.6%), see Table 22:

Table 22 body weight change and life quality change situation

Body weight (%)			Ka Shi mark (%)
Body weight (%)			Ka Shi mark (%)			Raise	Constant	Descend	Raise	Constant	Descend
Treatment group chemotherapy group beauty group	45(14.9) 3(3.0) 4(13.3)	214(70.9) 68(68.0) 12(40.0)	43(14.2) 29(29.0)* 14(46.7)*	42(13.9) 5(5.0) 3(10.0)	225(84.5) 55(55.0) 19(63.3)	Raise	Constant	Descend	Raise	Constant	Descend	35(11.6) 40(40.0)* 8(26.7)*

*p＜0.01

4, hemopoietic function changes:

(1) leukocyte (WBC) changes: WBC does not have significant change before and after the treatment of treatment group, and the TIANXIAN WAN group does not have significant change yet, and chemotherapy group is treated back WBC p＜0.05 that obviously descends, and compares significant difference with the treatment group, sees Table 23:

Change relatively before and after the treatment of table 23 leukocyte

(2) hematochrome (HB) changes: the HB variation changes basically identical with WBC, and treatment group and TIANXIAN WAN group have no significant change, and than not statistically significant, back chemotherapy group HB is visible obviously to descend and treat before and after the treatment, and there were significant differences with the matched group ratio, sees Table 24:

Change relatively before and after the treatment of table 24 hematochrome

5, electrocardiogram and hepatic and renal function change:

Treatment group treatment back electrocardiogram shows no significant change, checks before the treatment in 302 examples that 2 routine sinus tachycardias, 1 example are sporadic room morning, and 1 example is that LB can the property conduction block, keeps former conclusion after the treatment; Treatment back 2 examples abnormal liver function occurs and account for 0.66%, and wherein 1 example is a liver cancer patient, and 1 example is that shift in intestinal cancer extensive abdominal cavity in late period, so be not thought of as medicamentous liver lesion; Urine protein (++) appears in 1 example in 302 examples, but BUN is normal; Above situation shows that this medicine does not have influence to heart, hepatic and renal function.

From efficacy analysis, the treatment group is stable to take a turn for the better apparently higher than matched group, and two groups are respectively 78.15% and 61.54%, p＜0.05, and this medicine effect is better than the drug combination of known Chinese medicine medicine for preventing TIANXIAN WAN and known anticancer Western medicine; Can be observed the gastric cancer effect by different sick kinds and obviously be better than matched group, p＜0.05; Different differentiation of symptoms and signs for classification of syndrome show resistance of the expectorant stasis of blood and stagnation of QI patient curative effect better, prove that this medicine is used for all blood stasis syndrome patients more; This medicine has protective effect to hemogram, and WBC, HB, BPC do not have significant change p＜0.05 before and after the treatment, and the WBC of matched group and HB all obviously descend, and have compared significant difference for two groups; The darling renal function result shows that this medicine is harmless to the conscience kidney before and after the treatment; Treatment back body weight change is little, obviously descends with the matched group body weight and has compared statistical significance; Karnofsky scoring discloses the treatment group does not have influence to life quality, and matched group life quality p＜0.05 that obviously descends; This medicine non-evident effect.

The result shows that pharmaceutical composition of the present invention has anticancer and cancer suppressing action; be particularly useful for the Infusion in Patients with Digestive in late period; its avirulence; safe and reliable; can overcome the digestive tract side reaction that chemotherapy is brought; hemogram and immunologic function are had protective effect, and particularly evident for blood stasis syndrome patient curative effect, it can become a kind of new antineoplastic Chinese traditional medicine.

Description of drawings

Fig. 1 matched group adenocarcinoma of lung has abundant smooth surfaced endoplasmic reticulum and numerous mucocysts, and can see lysosome.

Fig. 2 contrasts to adenocarcinoma of lung, and mucocyst is fused into the mucus lake, and nuclear is extruded into polygon, and mitochondrion is sandwiched between the mucus paste.

Fig. 3 matched group lung squamous cancer, the cell boundaries confusion, iuntercellular connects with desmosome, is rich in micro-filament and glycogen granule in the cell, and mitochondrion has vacuolar degeneration.

Fig. 4 matched group lung squamous cancer has two significant big kernels, is rich in euchromatin, perinuclear space broadening, and mitochondrion has swelling phenomenon and vacuolar degeneration.

Fig. 5 treatment group adenocarcinoma of lung, neutrophilic granulocyte merges disappearance with the cell membrane that cancerous cell contacts both closely.

Fig. 6 treatment group adenocarcinoma of lung, the cancerous cell disintegrate, cell Lu and mucocyst loose from, be split into bare nucleus.

Fig. 7 treatment group adenocarcinoma of lung, the bare nucleus of cancerous cell is by the tight embedding of collagen fiber.

Fig. 8 treatment group adenocarcinoma of lung, cancerous cell are downright bad in flakes.

Fig. 9 treatment group lung squamous cancer, lymphocyte contacts closely with cancerous cell, and cancer cell membrane molten breakthrough occurs and loses.

Figure 10 treatment group lung squamous cancer, the cancerous cell disintegrate, organelle loose from, bare nucleus breaks.

Figure 11 treatment group lung squamous cancer, lymphocyte are invaded in the cancer nests, insert between the cancerous cell.

Figure 12 treats lung squamous cancer, and cancerous cell is downright bad in flakes.

Figure 13 is to the influence of Turnover of Mouse Peritoneal Macrophages phagocytic function

The different sick stable curative effect improvement rate comparison diagrams of planting of Figure 14

Different typing progressive stage comparison diagrams between two groups of Figure 15

Figure 16 symptom variation analysis chart

Following embodiment all can realize the effect of above-mentioned experimental example.

The specific embodiment

Embodiment 1: the preparation of capsule

Artificial Calculus Bovis 0.6g Flos Lonicerae 38g Scolopendra 1g Squama Manis 18g Venenum Bufonis 2.5g

Herba Taraxaci 56g Herba Scutellariae Barbatae 8g Pseudobulbus Cremastrae Seu Pleiones 18g Rhizoma Curcumae 18g Herba Hedyotidis Diffusae 38g

Radix Sophorae Flavescentis 48g Herba Solani Nigri 30g Margarita 0.3g Radix Et Rhizoma Rhei 18g Rhizoma Dioscoreae Bulbiferae 6g

Olibanum 3g Myrrha 3g Rhizoma Corydalis 28g Flos Carthami 4g Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens) 38g

Radix Codonopsis 54g Radix Astragali 66g Radix Et Caulis Acanthopanacis Senticosi 56g Fructus Amomi 12g

Get above-mentioned 24 flavor crude drug, earlier Flos Lonicerae, Herba Taraxaci, Herba Scutellariae Barbatae, Herba Hedyotidis Diffusae, Radix Sophorae Flavescentis, Herba Solani Nigri, Rhizoma Dioscoreae Bulbiferae, the Radix Astragali and Radix Et Caulis Acanthopanacis Senticosi are decocted with water three times, 2 hours for the first time, 1.5 hours for the second time, 1 hour for the third time, collecting decoction filters, and it is 1.20～1.25 clear paste that filtrate decompression is condensed into 75 ℃ of following relative densities; Olibanum, Myrrha heating are dissolved, filter with Coarse Mesh Gauze, filtrate merges, and adds in the above-mentioned clear paste; Artificial Calculus Bovis, Margarita are ground into impalpable powder; All the other Scolopendras etc. ten are ground into fine powder simply, with above-mentioned impalpable powder mixing, add in the clear paste, stir, and drying is ground into fine powder, and mixing incapsulates, promptly; Oral when taking, each 3,3 times on the one, warm water delivery service after meal, 6 weeks were a course of treatment.

Embodiment 2: the preparation of tablet

Artificial Calculus Bovis 0.9g Flos Lonicerae 21g Scolopendra 0.6g Squama Manis 28g Venenum Bufonis 4.5g

Herba Taraxaci 32g Herba Scutellariae Barbatae 6g Pseudobulbus Cremastrae Seu Pleiones 28g Rhizoma Curcumae 28g Herba Hedyotidis Diffusae 21g

Radix Sophorae Flavescentis 31g Herba Solani Nigri 48g Margarita 0.4g Radix Et Rhizoma Rhei 12g Rhizoma Dioscoreae Bulbiferae 4g

Olibanum 4g Myrrha 4g Rhizoma Corydalis 12g Flos Carthami 2g Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens) 48g

Radix Codonopsis 68g Radix Astragali 42g Radix Et Caulis Acanthopanacis Senticosi 32g Fructus Amomi 18g

The above-mentioned raw materials medicine is added conventional adjuvant according to a conventional method make tablet.

Embodiment 3: the preparation of granule

Artificial Calculus Bovis 0.2g Flos Lonicerae 48g Scolopendra 1.8g Squama Manis 12g Venenum Bufonis 1.5g

Herba Taraxaci 76g Herba Scutellariae Barbatae 14g Pseudobulbus Cremastrae Seu Pleiones 12g Rhizoma Curcumae 12g Herba Hedyotidis Diffusae 48g

Radix Sophorae Flavescentis 68g Herba Solani Nigri 12g Margarita 0.2g Radix Et Rhizoma Rhei 28g Rhizoma Dioscoreae Bulbiferae 8g

Olibanum 2g Myrrha 2g Rhizoma Corydalis 38g Flos Carthami 6g Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens) 22g

Radix Codonopsis 32g Radix Astragali 88g Radix Et Caulis Acanthopanacis Senticosi 78g Fructus Amomi 6g

The above-mentioned raw materials medicine is added conventional adjuvant according to a conventional method make granule.

Embodiment 4: the preparation of pill

The above-mentioned raw materials medicine is added conventional adjuvant according to a conventional method make pill.

Embodiment 5: the discrimination method of medicament composition capsule content of the present invention and content assaying method

Differentiate:

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=18: 18: 70: 0.1; The detection wavelength is 220nm; Number of theoretical plate calculates by the matrine peak should be not less than 8000; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 10mg of phosphorus pentoxide drying under reduced pressure to constant weight, puts in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 3ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Every 1ml contains matrine 60 μ g; The preparation of need testing solution: get the medicament composition capsule content of the present invention under the content uniformity item, grind well, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 2ml and make moistening, add chloroform 25ml again, supersound process 20 minutes filters, and residue and container, filter wash 4 times with chloroform, each 5ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; Every capsules content contains Radix Sophorae Flavescentis in matrine C 15H 24N 20, must not be less than 0.16mg.

Embodiment 6: the discrimination method of medicament composition capsule content of the present invention

Differentiate:

D. get medicament composition capsule content 3g of the present invention, add chloroform 25ml, reflux, extract, 5 hours filters, and adds active carbon 0.3g in the filtrate, and jolting was placed 30 minutes, filtered, and filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 2 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=4: 3: 3 was developing solvent, launched, and took out, dry, spray, is put under the 365nm ultraviolet light and is inspected 105 ℃ of bakings 3-4 minute with 10% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle.

Embodiment 7: the content assaying method of medicament composition capsule content of the present invention

Assay:

Embodiment 8: the discrimination method of medicament composition capsule content of the present invention and content assaying method

Differentiate:

Assay:

Embodiment 9: the discriminating of medicament composition capsule content of the present invention and content assaying method

Differentiate:

A. get medicament composition capsule content 4g of the present invention, add methanol 20ml, flooded 10 minutes, filter, get filtrate 10ml, evaporate to dryness, residue adds water 10ml makes dissolving, adds hydrochloric acid 1ml again, puts in the water-bath reflux 30 minutes, cooling immediately, divide 2 extractions with ether 20ml, merge ether extracted liquid, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, upper solution with 30 ~ 60 ℃ of petroleum ether-Ethyl formate-formic acid=15: 5: 1 is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes redness;

B. get medicament composition capsule content 5g of the present invention, add strong ammonia solution 1ml and chloroform 20ml, flooded 1 hour, jolting constantly filters, and filtrate evaporate to dryness, residue add ethanol 5ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 20 μ l, reference substance solution 1 μ l, put respectively on same silica gel g thin-layer plate, with normal hexane-chloroform-methanol=10: 6: 1 was developing solvent, launched, and took out, dry, put in the iodine vapor the smoked several seconds after, put under the 365nm ultraviolet light and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

C. get medicament composition capsule content 3g of the present invention, add chloroform 25ml, reflux, extract, 5 hours filters, and adds active carbon 0.3g in the filtrate, and jolting was placed 30 minutes, filtered, and filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 2 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=4: 3: 3 was developing solvent, launched, and took out, dry, spray, is put under the 365nm ultraviolet light and is inspected 105 ℃ of bakings 3-4 minute with 10% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle;

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=18: 18: 70: 0.1; The detection wavelength is 220nm; Number of theoretical plate calculates by the matrine peak should be not less than 8000; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 10mg of phosphorus pentoxide drying under reduced pressure to constant weight, puts in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 3ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Every 1ml contains matrine 60 μ g; The preparation of need testing solution: get the medicament composition capsule content of the present invention under the content uniformity item, grind well, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 2ml and make moistening, add chloroform 25ml again, supersound process 20 minutes filters, and residue and container, filter wash 4 times with chloroform, each 5ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; The every capsules content of this product contains Radix Sophorae Flavescentis in matrine C 15H 24N20, must not be less than 0.16mg.

Embodiment 10: the discriminating of medicament composition capsule content of the present invention and content assaying method

Differentiate:

Assay:

Embodiment 11: the discriminating of medicament composition capsule content of the present invention and content assaying method

Differentiate:

Assay:

Claims

1. pharmaceutical composition is characterized in that this pharmaceutical composition crude drug consists of:

2. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition crude drug consists of:

3. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition crude drug consists of:

4. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition crude drug consists of:

5. as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that getting this pharmaceutical composition crude drug, add conventional adjuvant,, make capsule, powder, tablet, granule, pill or oral liquid according to common process.

6. as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that this preparation of drug combination method is:

Get crude drug, earlier Flos Lonicerae, Herba Taraxaci, Herba Scutellariae Barbatae, Herba Hedyotidis Diffusae, Radix Sophorae Flavescentis, Herba Solani Nigri, Rhizoma Dioscoreae Bulbiferae, the Radix Astragali and Radix Et Caulis Acanthopanacis Senticosi are decocted with water three times, 1-3 hour for the first time, 0.5-2 hour for the second time, 0.5-1.5 hour for the third time, collecting decoction filters, and it is 1.00～1.50 clear paste that filtrate decompression is condensed into 50-90 ℃ of following relative density; Olibanum, Myrrha heating are dissolved, filter, filtrate merges, and adds in the above-mentioned clear paste; Artificial Calculus Bovis, Margarita are ground into impalpable powder; All the other crude drug are ground into fine powder, with above-mentioned impalpable powder mixing, add in the clear paste, stir, and drying is ground into fine powder, and mixing adds conventional adjuvant and makes capsule, powder, tablet, granule, pill or oral liquid.

7. pharmaceutical composition as claimed in claim 6 is characterized in that this preparation of drug combination method is:

Get crude drug, earlier Flos Lonicerae, Herba Taraxaci, Herba Scutellariae Barbatae, Herba Hedyotidis Diffusae, Radix Sophorae Flavescentis, Herba Solani Nigri, Rhizoma Dioscoreae Bulbiferae, the Radix Astragali and Radix Et Caulis Acanthopanacis Senticosi are decocted with water three times, 2 hours for the first time, 1.5 hours for the second time, 1 hour for the third time, collecting decoction filters, and it is 1.20～1.25 clear paste that filtrate decompression is condensed into 75 ℃ of following relative densities; Olibanum, Myrrha heating are dissolved, filter, filtrate merges, and adds in the above-mentioned clear paste; Artificial Calculus Bovis, Margarita are ground into impalpable powder; All the other crude drug are ground into fine powder, with above-mentioned impalpable powder mixing, add in the clear paste, stir, and drying is ground into fine powder, and mixing adds conventional adjuvant and makes capsule, powder, tablet, granule, pill or oral liquid.

8. as the arbitrary described pharmaceutical composition of claim 1-4, the method for quality control that it is characterized in that this pharmaceutical composition comprises one or more in following discriminating or the assay:

Differentiate:

A. the compositions capsule 's content of getting it filled, put microscopically and observe: the pollen grain similar round, short thorn of diameter 30-80 μ m outer wall tool and point-like are carved stricture of vagina, and 3 germinal aperatures are arranged; Endotesta stone cell brownish red, the class polygon is seen on the surface, and wall thickness, cell contain siliceous; Unsetting fragment is near colourless or faint yellow, and similar round not of uniform size, ellipse or irregular shape cavity are arranged mostly; Calcium oxalate cluster crystal is big, diameter 40-160 μ m; Sclerenchyma fragment green-yellow, cell class polygon or slightly prolongation, wall is crooked slightly, and the beaded that has thickens, and pit is fine and closely woven; Connect latex dust, diameter 10-20 μ m contains fine particle shape thing; Irregular fragment is translucent, and is glossy, and the surface shows graininess, the visible fine texture that has;

B. the compositions capsule 's content 2-6g that gets it filled adds methanol 10-30ml, floods 5-15 minute, filter, get filtrate 5-15ml, evaporate to dryness, residue adds water 5-15ml makes dissolving, adds hydrochloric acid 1ml again, puts in the water-bath reflux 20～40 minutes, cooling immediately, divide 2 extractions with ether 10-30ml, merge ether extracted liquid, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 2-7 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 20-80 ℃ of petroleum ether-Ethyl formate-formic acid=10-20: 3-8: 1 upper solution is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes redness;

C. the compositions capsule 's content 2-7g that gets it filled adds strong ammonia solution 1ml and chloroform 10-30ml, floods 1 hour, and jolting constantly filters, and filtrate evaporate to dryness, residue add ethanol 2-7ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10-30 μ l, reference substance solution 1 μ l, put respectively on same silica gel g thin-layer plate, with normal hexane-chloroform-methanol=5-15: 3-9: 1 is developing solvent, launch, take out, dry, after putting in the iodine vapor the smoked several seconds, put under the 365nm ultraviolet light and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

D. the compositions capsule 's content 1-5g that gets it filled adds chloroform 15-50ml, reflux, extract, 3-7 hour, filters, add active carbon 0.1-0.5g in the filtrate, jolting was placed 15-45 minute, filtered, filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 1-3mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 5-15 μ l, reference substance solution 1-3 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=2-6: 2-4: 2-4 is developing solvent, launches, and takes out, dry, spray, is put under the 365nm ultraviolet light and is inspected 90-120 ℃ of baking 2-6 minute with the 5-15% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle;

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=10-30: 10-30: 50-90: 0.1; The detection wavelength is 220nm; Number of theoretical plate calculates by the matrine peak should be not less than 8000; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 5-15mg of phosphorus pentoxide drying under reduced pressure to constant weight, put in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 1-5ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, that is, every 1ml contains matrine 40-80 μ g; The preparation of need testing solution: get the medicament composition capsule content under the content uniformity item, grind well, get 0.2-0.8g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 1-3ml and make moistening, add chloroform 10-40ml again, supersound process 10-30 minute, filter, residue and container, filter wash 2-6 time with chloroform, each 3-7ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 5-15 μ l of need testing solution of drawing injects chromatograph of liquid, measures, promptly; Every capsules content contains Radix Sophorae Flavescentis in matrine C15H24N2O, must not be less than 0.16mg.

9. pharmaceutical composition as claimed in claim 8, the method for quality control that it is characterized in that this pharmaceutical composition comprises one or more in following discriminating or the assay:

Differentiate:

A. the compositions capsule 's content of getting it filled, put microscopically and observe: the pollen grain similar round, short thorn of diameter 43～66 μ m outer wall tools and point-like are carved stricture of vagina, and 3 germinal aperatures are arranged; Endotesta stone cell brownish red, the class polygon is seen on the surface, and wall thickness, cell contain siliceous; Unsetting fragment is near colourless or faint yellow, and similar round not of uniform size, ellipse or irregular shape cavity are arranged mostly; Calcium oxalate cluster crystal is big, diameter 60～140 μ m; Sclerenchyma fragment green-yellow, cell class polygon or slightly prolongation, wall is crooked slightly, and the beaded that has thickens, and pit is fine and closely woven; Connect latex dust, diameter 12～15 μ m contain fine particle shape thing; Irregular fragment is translucent, and is glossy, and the surface shows graininess, the visible fine texture that has;

B. the compositions capsule 's content 4g that gets it filled adds methanol 20ml, floods 10 minutes, filter, get filtrate 10ml, evaporate to dryness, residue adds water 10ml makes dissolving, adds hydrochloric acid 1ml again, puts in the water-bath reflux 30 minutes, cooling immediately, divide 2 extractions with ether 20ml, merge ether extracted liquid, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, upper solution with 30～60 ℃ of petroleum ether-Ethyl formate-formic acid=15: 5: 1 is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes redness;

C. the compositions capsule 's content 5g that gets it filled adds strong ammonia solution 1ml and chloroform 20ml, floods 1 hour, and jolting constantly filters, and filtrate evaporate to dryness, residue add ethanol 5ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 20 μ l, reference substance solution 1 μ l, put respectively on same silica gel g thin-layer plate, with normal hexane-chloroform-methanol=10: 6: 1 was developing solvent, launched, and took out, dry, put in the iodine vapor the smoked several seconds after, put under the 365nm ultraviolet light and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

D. the compositions capsule 's content 3g that gets it filled adds chloroform 25ml, and reflux, extract, 5 hours filters, and adds active carbon 0.3g in the filtrate, and jolting was placed 30 minutes, filtration, and filtrate is concentrated into dried, and residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets the bufogenin reference substance, and chlorination is copied into the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 2 μ l, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-chloroform-acetone=4: 3: 3 was developing solvent, launched, and took out, dry, spray, is put under the 365nm ultraviolet light and is inspected 105 ℃ of bakings 3-4 minute with 10% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical green-yellow fluorescence speckle;

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile-methanol-pH6.8 phosphate buffer-triethylamine=18: 18: 70: 0.1; The detection wavelength is 220nm; Number of theoretical plate calculates by the matrine peak should be not less than 8000; The preparation of reference substance solution: precision takes by weighing through the matrine reference substance 10mg of phosphorus pentoxide drying under reduced pressure to constant weight, puts in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shake up, precision is measured 3ml, puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Every 1ml contains matrine 60 μ g; The preparation of need testing solution: get the medicament composition capsule content under the content uniformity item, grind well, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, adds ammonia 2ml and make moistening, add chloroform 25ml again, supersound process 20 minutes filters, and residue and container, filter wash 4 times with chloroform, each 5ml, filter, filtrate merges, and puts evaporate to dryness in the water-bath, residue is with dissolve with methanol and be transferred in the 10ml measuring bottle, be diluted to scale with methanol, shake up, filter, get subsequent filtrate, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; Every capsules content contains Radix Sophorae Flavescentis in matrine C15H24N2O, must not be less than 0.16mg.

10. as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that wherein Olibanum, Myrrha or Rhizoma Corydalis replace with Olibanum (processed), Myrrha (processed) or Rhizoma Corydalis (processed); Squama Manis is for concocting Squama Manis.

11. as the application of the arbitrary described pharmaceutical composition of claim 1-4 in preparation antitumor and immune drug.