CN102302718B - Antitumor medicinal composition and preparation method thereof - Google Patents
Antitumor medicinal composition and preparation method thereof Download PDFInfo
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- CN102302718B CN102302718B CN2011102428458A CN201110242845A CN102302718B CN 102302718 B CN102302718 B CN 102302718B CN 2011102428458 A CN2011102428458 A CN 2011102428458A CN 201110242845 A CN201110242845 A CN 201110242845A CN 102302718 B CN102302718 B CN 102302718B
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Abstract
The invention provides an antitumor medicinal composition and a preparation method thereof. The antitumor medicinal composition contains rhizoma typhonii, ginseng, common burreed rhizome, astragalus, vietnamese sophora root, paris polyphylla, isatis root, indian iphigenia bulb, barbed skullcap herb, honeysuckle, rhizome corydalis and herba leonuri. The antitumor medicinal composition has the comprehensive anticancer effects of dissipating hard mass, strengthening resistance and solidifying health, promoting qi circulation and removing blood stasis, and clearing heat and detoxicating through the synergistic effects of raw materials. The antitumor medicinal composition has obvious inhibiting effects on the growth of s180 sarcoma and H22 liver cancer and a remarkable antitumor effect.
Description
Technical field
The present invention relates to field of traditional Chinese, particularly a kind of antineoplastic pharmaceutical compositions and preparation method thereof; In described antineoplastic pharmaceutical compositions, contain: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri.
Background technology
Tumor is as a kind of malignant disease of serious danger side of body human life health, become one of commonly encountered diseases that sickness rate is the highest, frequently-occurring disease, and its sickness rate and mortality rate are always in rising trend, and its sickness rate increases year by year, seriously endangers the whole mankind's life and health.Estimate that according to World Health Organization (WHO) the whole world dies from this patient and reach 6,900,000 people every year, the patient that China dies from primary disease every year also approaches 2,000,000.So great research topic in the treatment whole world medical domain of tumor.The nearest statistics of China shows, the death toll that tumor causes oneself through surpassing cardiovascular disease, the first place that occupies city and urban residents' cause of the death.The treatment of malignant tumor be take traditional operation, radiation and chemotherapy as main, above Therapeutic Method all has limitation: although radiotherapy can killing off tumor cells, short-term suppresses its propagation, chemicals in chemotherapy also has certain therapeutic effect to some tumors, but the specificity of effect is low, in the time of killing tumor cell, also suppress the activity of human normal tissue cell, so most of medicine has serious toxic and side effects.
Chinese medicine has its superiority in this respect, not only has minimum toxic and side effects, and Chinese medicine contains Multiple components simultaneously, has the characteristics of multipath, too many levels and many target spots, can suppress from integral body generation, the development of tumor.Chinese medicine and pharmacy be the Chinese nation with disease long-term struggle process in the treasure that accumulates, of long standing and well established, of extensive knowledge and profound scholarship.Applicating history is long, and oneself process verifies its safety and efficacy.The cause of disease, pathogenesis, determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs and the principle-method-recipe-medicines of Chinese medicine and pharmacy to cancer, have unique theory and experience, and none does not enrich deep science philosophic theory abrim.Especially modern age, centering medical applications modern science and technology were carried out system, deep research, had inherited, developed theory and the method for Chinese medicine treatment carcinoma.
(application number: 200680018061.4) disclose a kind of herbal-composition, it comprises Rhizoma Curcumae (Curcumae kwangsiensis), Herba Dendrobii (Herba Dendrovbii nobile Lindl.), Rhizoma Pinelliae Preparatum (Rhizoma Pinelliae preparatum), Rhizoma Typhonii (Rhizoma Typhonii) and other optional medical herbs to Chinese patent application " for the herbal-composition for the treatment of of cancer ".Described compositions can be processed to certain form, for being applied to the cancer patient to improve their health.But the synergy in this herbal-composition between various crude drug is not obvious, cause the curative effect of tumor limited.So, need in the market a kind of to the significant antineoplastic pharmaceutical compositions of tumor efficiency.
Summary of the invention
The purpose of this invention is to provide and be particularly related to a kind of antineoplastic pharmaceutical compositions and preparation method thereof; In described antineoplastic pharmaceutical compositions, contain: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri.Synergism between each raw material in the present invention, comprehensively reach the anticancer effect of loose hard soft junction, strengthening the body resistance, regulating qi to disperse stagnation, heat-clearing and toxic substances removing.
The objective of the invention is to realize by following technical scheme:
A kind of antineoplastic pharmaceutical compositions, contain in the crude drug of described antineoplastic pharmaceutical compositions: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is: Rhizoma Typhonii 200-450, Radix Ginseng 100-150, Rhizoma Sparganii 100-150, Radix Astragali 100-150, Radix Sophorae Tonkinensis 100-150, Rhizoma Paridis 100-150, Radix Isatidis 100-150, Pseudobulbus Cremastrae Seu Pleiones 40-80, Herba Scutellariae Barbatae 40-80, Flos Lonicerae 40-80, Rhizoma Corydalis 40-80, Herba Leonuri 40-80.
Described Rhizoma Typhonii, Rhizoma Corydalis are by current edition pharmacopeia processed product, and wherein Rhizoma Corydalis is vinegar system.
The dosage form of described antineoplastic pharmaceutical compositions can be oral solutions, capsule.
Another object of the present invention is achieved through the following technical solutions:
The dosage form of described antineoplastic pharmaceutical compositions is oral solutions, and preparation process is as follows:
A kind of antineoplastic pharmaceutical compositions, contain in the crude drug of described antineoplastic pharmaceutical compositions: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri; The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is: Rhizoma Typhonii 200-450, Radix Ginseng 100-150, Rhizoma Sparganii 100-150, Radix Astragali 100-150, Radix Sophorae Tonkinensis 100-150, Rhizoma Paridis 100-150, Radix Isatidis 100-150, Pseudobulbus Cremastrae Seu Pleiones 40-80, Herba Scutellariae Barbatae 40-80, Flos Lonicerae 40-80, Rhizoma Corydalis 40-80, Herba Leonuri 40-80;
Preparation method comprises the following steps:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
C, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25(50-60 ℃);
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply crude drug except the merging of ethanol supernatant and described Rhizoma Typhonii percolate, then carry out cold preservation processing, filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to the preparation processing, obtain the antineoplastic pharmaceutical compositions oral liquid.
Another object of the present invention is achieved through the following technical solutions:
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A kind of antineoplastic pharmaceutical compositions, contain in the crude drug of described antineoplastic pharmaceutical compositions: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri; The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is: Rhizoma Typhonii 200-450, Radix Ginseng 100-150, Rhizoma Sparganii 100-150, Radix Astragali 100-150, Radix Sophorae Tonkinensis 100-150, Rhizoma Paridis 100-150, Radix Isatidis 100-150, Pseudobulbus Cremastrae Seu Pleiones 40-80, Herba Scutellariae Barbatae 40-80, Flos Lonicerae 40-80, Rhizoma Corydalis 40-80, Herba Leonuri 40-80;
Preparation method comprises the following steps:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
C, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25(50-60 ℃);
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
The present invention has following beneficial effect compared to existing technology:
Between the crude drug that the present invention adopts, synergy is obvious, comprehensively reaches the anticancer effect of loose hard soft junction, strengthening the body resistance, regulating qi to disperse stagnation, heat-clearing and toxic substances removing; The present invention all has obvious inhibitory action to the growth of s180 sarcoma and H 22 hepatocarcinoma, and antitumor curative effect is remarkable.
The specific embodiment
Embodiment 1:
A kind of antineoplastic pharmaceutical compositions, contain in the crude drug of described antineoplastic pharmaceutical compositions: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is: Rhizoma Typhonii 200-450, Radix Ginseng 100-150, Rhizoma Sparganii 100-150, Radix Astragali 100-150, Radix Sophorae Tonkinensis 100-150, Rhizoma Paridis 100-150, Radix Isatidis 100-150, Pseudobulbus Cremastrae Seu Pleiones 40-80, Herba Scutellariae Barbatae 40-80, Flos Lonicerae 40-80, Rhizoma Corydalis 40-80, Herba Leonuri 40-80.
Described Rhizoma Typhonii, Rhizoma Corydalis are by current edition pharmacopeia processed product, and wherein Rhizoma Corydalis is vinegar system.
The dosage form of described antineoplastic pharmaceutical compositions can be oral solutions, capsule.
The technical scheme of the present embodiment is to form in long-term clinical practice, reasonable recipe, motherland's medical science think the formation of carcinoma and deficiency of vital QI, visceral dysfunction, exopathogen be detained and cause qi depression to blood stasis, stagnant heat poison poly-, mutually fight knot, accumulate to amass in interior extremely close relationship arranged.Because the generation of carcinoma and development have close internal relation with void, the stasis of blood, expectorant, poison, therefore should focus on strengthening the body resistance, blood circulation promoting and blood stasis dispelling, resolving phlegm and softening hard masses, heat-clearing and toxic substances removing when treating tumor." the positive deficiency of vital energy is diagenesis " (" just curing volume outward "); " tripe fu jie piece must tangible blood " (Wang Qingren); " there is the piece ordinary person's body upper, middle and lower person, be mostly expectorant " (" danxi's experiential therapy "); Pyretic toxicity pents up, and stagnant difficultyization of poison, gather and do not go, and of a specified duration becomes to amass piece, and therefore, tonify deficiency, blood stasis dispelling, to reduce phlegm, detoxify be the important method for the treatment of tumor.
The theoretical basis of the above-mentioned raw materials that the present embodiment is selected is:
Because the generation of carcinoma and development have close internal relation with void, the stasis of blood, expectorant, poison, therefore should focus on strengthening the body resistance, blood circulation promoting and blood stasis dispelling, resolving phlegm and softening hard masses, heat-clearing and toxic substances removing when treating tumor.The present embodiment pharmaceutical composition, according to above-mentioned theory of Chinese medical science composition of prescription, be take Rhizoma Typhonium Gigantei (Rhizoma Typhonii), Radix Ginseng blood stasis dispelling, eliminating stagnation, tonifying vital QI as main; Be equipped with Rhizoma Sparganii blood stasis dispelling removing food stagnancy, the spleen reinforcing of Radix Astragali QI invigorating; Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, heat-clearing and toxic substances removing, reducing swelling and alleviating pain; The Herba Leonuri blood circulation promoting and blood stasis dispelling.Comprehensively reach the anticancer effect of loose hard soft junction, strengthening the body resistance, regulating qi to disperse stagnation, heat-clearing and toxic substances removing.
The pharmacological testing of the antineoplastic pharmaceutical compositions of the present embodiment is as follows:
The antineoplastic pharmaceutical compositions of the present embodiment is crude drug 15,30 at dosage, 50 gkg
-1the time, the growth of mice s180 sarcoma and H 22 hepatocarcinoma is all had to inhibitory action, and order increasing along with dosage, tumor killing effect strengthens, and presents obvious dose-effect relationship, wherein, 30,50 gkg
-1obvious to s180 sarcoma inhibitory action, the heavy suppression ratio of tumor is respectively 36. 1% and 49. 8%; 15,30,50 gkg
-1obvious to H 22 hepatocarcinoma inhibitory action, the heavy suppression ratio of tumor is respectively 36.2%, 45. 7% and 52.3%.
The antineoplastic pharmaceutical compositions of the present embodiment is as follows to mice s180 sarcoma pharmacological action test:
I, medicinal liquid preparation:
A, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10, is preferably 1:8; The concentration of described alcoholic solution is 60%-95%, is preferably 70%;
B, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12, are preferably 1:10; The number of times that described decoction is processed is 2 times, and each time is 1-4 hour, is preferably 2 hours, merges the decocting liquid at every turn obtained, as all the other ten decocting liquids of crude drug simply;
C, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25(50-60 ℃);
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol; Described all the other containing ethanol are ten simply in the concentrated solution of crude drug, and described ethanol content is 60%-90%, is preferably 70%;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, then remove Ethanol Treatment, obtain ten simply crude drug remove the ethanol supernatant; In described standing processing, temperature is room temperature, and the time is 24～60 hours, is preferably 48 hours;
F, by described ten simply crude drug except the merging of ethanol supernatant and described Rhizoma Typhonii percolate, then carry out concentration, the concentrated solution obtained is the antineoplastic pharmaceutical compositions medicinal liquid.
II, the test of mice s180 sarcoma:
The aseptic mouse ascites of getting s180 sarcoma intraperitoneal inoculation growth 8d, with normal saline dilution oncocyte content to 3-4 * 10
7mL
-1, be inoculated in experiment mice right side armpit subcutaneous, every inoculation 0. 1 mL.The basic, normal, high dosage group of this pharmaceutical composition is adjusted into respectively gkg every days 15
-1, 30 gkg
-1, 50 gkg
-1, normal saline administration capacity is adjusted into 0.33 mL10 g
-1d
-1body weight, the administration cycle is 9d, grouping and administration situation, statistical method: 3 batches of tests merge statistics, with SPSS 10. 0 softwares, carry out statistical analysis, the experimental data of body weight and tumor weight with
± S means, with the one factor analysis of variance difference of each administration group and normal saline matched group relatively.Result is as follows:
Table 1: the antineoplastic pharmaceutical compositions medicinal liquid to the therapeutic outcome of mouse S 180 sarcoma (
± S, n=30)
Annotate: with the normal saline matched group, compare * P<0.01.
The antineoplastic pharmaceutical compositions of the present embodiment is as follows to mice H 22 hepatocarcinoma pharmacological action tests to antineoplastic pharmaceutical compositions:
I, medicinal liquid preparation: the method identical to employing in mice s180 sarcoma pharmacological action test with the antineoplastic pharmaceutical compositions of the present embodiment;
II, mice H 22 hepatocarcinoma tests:
Get the mouse ascites of H22 hepatocarcinoma intraperitoneal inoculation growth 9d, take normal saline dilution to oncocyte content as 5-6 * 10
7mL
-1inoculation N IH mice, the administration cycle is 11 d.Grouping and administration situation and statistical method are identical with the experiment of mice s180 sarcoma.The results are shown in following table:
Table 2: the antineoplastic pharmaceutical compositions medicinal liquid to mice H2 2 liver cancer treatment results (
± S, n=30)
Annotate: with the normal saline matched group, compare * P<0.01.
A kind of preparation method of antineoplastic pharmaceutical compositions, contain in the crude drug of described antineoplastic pharmaceutical compositions: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri; The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is: Rhizoma Typhonii 200-450, Radix Ginseng 100-150, Rhizoma Sparganii 100-150, Radix Astragali 100-150, Radix Sophorae Tonkinensis 100-150, Rhizoma Paridis 100-150, Radix Isatidis 100-150, Pseudobulbus Cremastrae Seu Pleiones 40-80, Herba Scutellariae Barbatae 40-80, Flos Lonicerae 40-80, Rhizoma Corydalis 40-80, Herba Leonuri 40-80;
The dosage form of described antineoplastic pharmaceutical compositions is oral solutions, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10, is preferably 1:8; The concentration of described alcoholic solution is 60%-95%, is preferably 70%;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12, are preferably 1:10; The number of times that described decoction is processed is 2 times, and each time is 1-4 hour, is preferably 2 hours, merges the decocting liquid at every turn obtained, as all the other ten decocting liquids of crude drug simply;
C, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25(50-60 ℃);
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol; Described all the other containing ethanol are ten simply in the concentrated solution of crude drug, and described ethanol content is 60%-90%, is preferably 70%; The concentration of described alcoholic solution is 95%;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant, in described standing processing, temperature is room temperature, the time is 24～60 hours, is preferably 48 hours;
F, by described ten simply crude drug except the merging of ethanol supernatant and described Rhizoma Typhonii percolate, then carry out cold preservation processing, filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions; During described cold preservation is processed, temperature is 0-4 ℃, and the time is 24～60 hours, is preferably 48 hours;
G, described total filtrate is carried out to the preparation processing, obtain the antineoplastic pharmaceutical compositions oral liquid.Described preparation is treated to, and will in described total filtrate, add antiseptic, adjusts total amount, obtains described tumors pharmaceutical combination oral liquid; Described antiseptic is potassium sorbate, and the weight ratio of described potassium sorbate and described total filtrate is 1.5-3:1000, is preferably 2:1000;
Described antiseptic can be also the conventional pharmaceutical preservatives such as sorbic acid;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10, is preferably 1:8; The concentration of described alcoholic solution is 60%-95%, is preferably 70%;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12, are preferably 1:10; The number of times that described decoction is processed is 2 times, and each time is 1-4 hour, is preferably 2 hours, merges the decocting liquid at every turn obtained, as all the other ten decocting liquids of crude drug simply;
C, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25(50-60 ℃);
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol; Described all the other containing ethanol are ten simply in the concentrated solution of crude drug, and described ethanol content is 60%-90%, is preferably 70%; The concentration of described alcoholic solution is 95%;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant, in described standing processing, temperature is room temperature, the time is 24～60 hours, is preferably 48 hours;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions; During described cold preservation is processed, temperature is 0-4 ℃, and the time is 24～60 hours, is preferably 48 hours;
G, described total filtrate is carried out to concentration, dried, add adjuvant, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule; Described adjuvant is magnesium stearate, and the percentage by weight that accounts for described capsule 's content is 0.15%～1%, is preferably 0.1%;
Described adjuvant can be also the conventional adjuvant of the capsules such as sodium carboxymethyl cellulose, soluble starch, calcium hydrogen phosphate;
In the present embodiment, the unit of weight of each raw material in described antineoplastic pharmaceutical compositions is gram, can be also kilogram;
In the present embodiment, the consumption of each raw material in described antineoplastic pharmaceutical compositions can be in the ratio range provided flexible combination, at this, do not enumerate one by one;
In the present embodiment, each raw material in described antineoplastic pharmaceutical compositions is conventional products, all can be in market and associated mechanisms buy and obtain;
In the present embodiment, equipment used is conventional equipment, all can on market, buy and obtain.
In the present embodiment, the overall process of described preparation method is carried out in the drug's GMP workshop.
Embodiment 2:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 375, Radix Ginseng 125, Rhizoma Sparganii 125, the Radix Astragali 125, Radix Sophorae Tonkinensis 125, Rhizoma Paridis 125, Radix Isatidis 125, Pseudobulbus Cremastrae Seu Pleiones 62.5, Herba Scutellariae Barbatae 62.5, Flos Lonicerae 62.5, Rhizoma Corydalis 62.5, Herba Leonuri 62.5.
Described Rhizoma Typhonii, Rhizoma Corydalis are by current edition pharmacopeia processed product, and wherein Rhizoma Corydalis is vinegar system.
In the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Embodiment 3:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 330, Radix Ginseng 130, Rhizoma Sparganii 130, the Radix Astragali 130, Radix Sophorae Tonkinensis 125, Rhizoma Paridis 130, Radix Isatidis 115, Pseudobulbus Cremastrae Seu Pleiones 60, Herba Scutellariae Barbatae 65, Flos Lonicerae 65, Rhizoma Corydalis 60, Herba Leonuri 60.
In the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Embodiment 4:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 450, Radix Ginseng 150, Rhizoma Sparganii 150, the Radix Astragali 150, Radix Sophorae Tonkinensis 100, Rhizoma Paridis 100, Radix Isatidis 100, Pseudobulbus Cremastrae Seu Pleiones 40, Herba Scutellariae Barbatae 40, Flos Lonicerae 40, Rhizoma Corydalis 40, Herba Leonuri 40.
In the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Embodiment 5:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 200, Radix Ginseng 100, Rhizoma Sparganii 100, the Radix Astragali 100, Radix Sophorae Tonkinensis 150, Rhizoma Paridis 150, Radix Isatidis 150, Pseudobulbus Cremastrae Seu Pleiones 80, Herba Scutellariae Barbatae 80, Flos Lonicerae 80, Rhizoma Corydalis 80, Herba Leonuri 80.
In the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Embodiment 6:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 400, Radix Ginseng 140, Rhizoma Sparganii 110, the Radix Astragali 140, Radix Sophorae Tonkinensis 110, Rhizoma Paridis 105, Radix Isatidis 105, Pseudobulbus Cremastrae Seu Pleiones 45, Herba Scutellariae Barbatae 50, Flos Lonicerae 45, Rhizoma Corydalis 45, Herba Leonuri 75;
[0040]in the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Embodiment 7:
The present embodiment is the preferred version on embodiment 1 basis, and the quality of raw materials used (component) is identical with embodiment 1, and the weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 250, Radix Ginseng 105, Rhizoma Sparganii 140, the Radix Astragali 110, Radix Sophorae Tonkinensis 145, Rhizoma Paridis 140, Radix Isatidis 140, Pseudobulbus Cremastrae Seu Pleiones 75, Herba Scutellariae Barbatae 80, Flos Lonicerae 75, Rhizoma Corydalis 75, Herba Leonuri 45.
In the present embodiment, the unit of weight of each raw material of described antineoplastic pharmaceutical compositions is gram, can be also kilogram.
When the dosage form of the present embodiment is oral solutions and capsule, preparation method is referring to embodiment 1.
Claims (5)
1. an antineoplastic pharmaceutical compositions, it is characterized in that: the crude drug of described antineoplastic pharmaceutical compositions is comprised of following medical material: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 330, Radix Ginseng 130, Rhizoma Sparganii 130, the Radix Astragali 130, Radix Sophorae Tonkinensis 125, Rhizoma Paridis 130, Radix Isatidis 115, Pseudobulbus Cremastrae Seu Pleiones 60, Herba Scutellariae Barbatae 65, Flos Lonicerae 65, Rhizoma Corydalis 60, Herba Leonuri 60;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
At C, 50-60 ℃ temperature, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25;
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
2. an antineoplastic pharmaceutical compositions, it is characterized in that: the crude drug of described antineoplastic pharmaceutical compositions is comprised of following medical material: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 450, Radix Ginseng 150, Rhizoma Sparganii 150, the Radix Astragali 150, Radix Sophorae Tonkinensis 100, Rhizoma Paridis 100, Radix Isatidis 100, Pseudobulbus Cremastrae Seu Pleiones 40, Herba Scutellariae Barbatae 40, Flos Lonicerae 40, Rhizoma Corydalis 40, Herba Leonuri 40;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
At C, 50-60 ℃ temperature, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25;
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
3. an antineoplastic pharmaceutical compositions, it is characterized in that: the crude drug of described antineoplastic pharmaceutical compositions is comprised of following medical material: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 200, Radix Ginseng 100, Rhizoma Sparganii 100, the Radix Astragali 100, Radix Sophorae Tonkinensis 150, Rhizoma Paridis 150, Radix Isatidis 150, Pseudobulbus Cremastrae Seu Pleiones 80, Herba Scutellariae Barbatae 80, Flos Lonicerae 80, Rhizoma Corydalis 80, Herba Leonuri 80;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
At C, 50-60 ℃ temperature, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25;
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
4. an antineoplastic pharmaceutical compositions, it is characterized in that: the crude drug of described antineoplastic pharmaceutical compositions is comprised of following medical material: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 400, Radix Ginseng 140, Rhizoma Sparganii 110, the Radix Astragali 140, Radix Sophorae Tonkinensis 110, Rhizoma Paridis 105, Radix Isatidis 105, Pseudobulbus Cremastrae Seu Pleiones 45, Herba Scutellariae Barbatae 50, Flos Lonicerae 45, Rhizoma Corydalis 45, Herba Leonuri 75;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
At C, 50-60 ℃ temperature, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25;
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
5. an antineoplastic pharmaceutical compositions, it is characterized in that: the crude drug of described antineoplastic pharmaceutical compositions is comprised of following medical material: Rhizoma Typhonii, Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri;
The weight ratio of each crude drug of described antineoplastic pharmaceutical compositions is:
Rhizoma Typhonii 250, Radix Ginseng 105, Rhizoma Sparganii 140, the Radix Astragali 110, Radix Sophorae Tonkinensis 145, Rhizoma Paridis 140, Radix Isatidis 140, Pseudobulbus Cremastrae Seu Pleiones 75, Herba Scutellariae Barbatae 80, Flos Lonicerae 75, Rhizoma Corydalis 75, Herba Leonuri 45;
The dosage form of described antineoplastic pharmaceutical compositions is capsule, and preparation process is as follows:
A, according to said ratio, described Rhizoma Typhonii is carried out to pulverization process, obtain the Rhizoma Typhonii coarse powder; Described Rhizoma Typhonii coarse powder is carried out to the percolation processing with alcoholic solution, and reclaim ethanol, obtain the Rhizoma Typhonii percolate; During described percolation is processed, the w/v of described Rhizoma Typhonii coarse powder and ethanol is 1:5-10;
B, according to said ratio, described Radix Ginseng, Rhizoma Sparganii, the Radix Astragali, Radix Sophorae Tonkinensis, Rhizoma Paridis, Radix Isatidis, Pseudobulbus Cremastrae Seu Pleiones, Herba Scutellariae Barbatae, Flos Lonicerae, Rhizoma Corydalis, Herba Leonuri are decocted to processing, obtain all the other ten decocting liquids of crude drug simply; During described decoction is processed, the gross weight of described all the other 11 flavor medicines and the w/v of water are 1:5-12;
At C, 50-60 ℃ temperature, by described all the other ten simply the decocting liquid of crude drug carry out filtration treatment, concentration, obtain all the other ten concentrated solutions of crude drug simply; The relative density of described concentrated solution is 1.1-1.25;
D, to described all the other ten add alcoholic solution in the concentrated solution of crude drug simply, obtain all the other ten concentrated solutions of crude drug simply containing ethanol;
E, by described containing ethanol all the other ten simply the concentrated solution of crude drug carry out standing processing, except Ethanol Treatment, obtain ten simply crude drug except the ethanol supernatant;
F, by described ten simply the supernatant of crude drug and described Rhizoma Typhonii percolate merge, then carry out filtration treatment, obtain described total filtrate; This total filtrate is described antineoplastic pharmaceutical compositions;
G, described total filtrate is carried out to concentration, dried, add adjuvant and antiseptic, then granulated, obtain capsule 's content; Described capsule 's content is incapsulated, obtain the antineoplastic pharmaceutical compositions capsule.
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| 中成药在肝癌放、化疗后的临床应用;戴德银等;《中国药业》;20071231;第16卷(第13期);第61-62页 * |
| 戴德银等.中成药在肝癌放、化疗后的临床应用.《中国药业》.2007,第16卷(第13期),第61-62页. |
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