CN100446802C - Crude drug for preventing tumor metastasis - Google Patents
Crude drug for preventing tumor metastasis Download PDFInfo
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- CN100446802C CN100446802C CNB2005101205387A CN200510120538A CN100446802C CN 100446802 C CN100446802 C CN 100446802C CN B2005101205387 A CNB2005101205387 A CN B2005101205387A CN 200510120538 A CN200510120538 A CN 200510120538A CN 100446802 C CN100446802 C CN 100446802C
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Abstract
The invention relates to a Chinese medicament for preventing tumor metastasis which is prepared from the following raw materials (by weight parts): alisol 40-80 parts, coix seed 350-450 parts, rabdosia 110-130 parts, baikal skullcap root 70-90 parts, ganoderma lucidum 430-530 parts, licorice root 40-80 parts. The preparing process consists steps of extracting, boiling, compressing, extract concrete, disintegrating and passing through 100 mesh sieves.
Description
Technical field
The present invention relates to medicine field, the natural drug that particularly a kind of prophylaxis of tumours shifts.
Background technology
Entered since 20th century, malignant tumor has become one of three big killers of harm humans health.According to relevant, cancer patient's five year survival rate is less than 50%, and main cause is the transfer of tumor.Patient's underwent operative of nearly 30% and the half a year after radiotherapy or the chemotherapy or 1 year, existing visible clinically metastatic lesion takes place.Clinical data shows that also 80% tumor patient is died from metastatic tumor.Up to the present, treatment and prevention to metastatic tumor also do not have a kind of effective method for treatment, even surgical operation, chemotherapy and radiation all are at a complete loss as to what to do to metastatic tumor.Therefore, tumor expert and pharmacy man numerous and confused conversion thinking are thought and must be set about from the generation development mechanism of metastatic tumor, seek new way and new breakthrough, fundamentally prevent and control the transfer of tumor,, reduce mortality rate to improve cancer patient's survival rate and quality of life.
One. the new way of oncotherapy---anti-new vessels generates anticancer method (Anti-Angiogenesis Therapy)
The Volkmann doctor of Harvard University and Boston children's hospital (Dr.Judah Folkman) is through the hardships research to " angiogenesis " problem in surplus 30 years, fruitful.He takes the lead in having proposed anti-new vessels and generates anticancer method.He finds under study for action: (1) growth of tumor is not successional, has two growth stages, does not promptly have the blood vessel stage and the blood vessel stage is arranged.Tumor is in the no blood vessel stage, and size is no more than 1～2mm
3, tumor cell number is no more than 10
6Individual, sustainable several months in this stage or do not wait for many years; When beginning new vessels to occur around the tumor, it just entered for the 2nd stage one the blood vessel stage, can increase rapidly, worsens and shift in this stage tumor.(2) tumor growth is that new vessels is dependent.The enlargement of tumor and transfer need new vessels to promote factor excitation to produce new vessels with the supply tumors of nutrients, and no matter any solid tumor all can't escape from this mechanism of angiogenesis and grow up, shifts and worsen.Therefore angiogenesis inhibitive factor (Angiogenesis Inhibitors) has just become the jinx of cancer.
The later stage nineties, Volkmann doctor and Ou Lirui (Dr.Michael S.O ' Reilly) successively publish an article on authoritative magazines such as " cell ", " science ", " nature " and report that they have found two kinds strong effectively angiogenesis inhibitors, angiogenesis blocker (Angiostatin) and endotheliocyte blockeres (Endostatin).Laboratory research shows does not have a kind of cancerous tissue of testing white mouse can escape the inhibition of angiogenesis inhibitive factor, and each tumor is all died of hunger the atrophy of disappearing.
Volkmann the doctor claim: the road of controlling in the future cancer is not limited to any, and anticarcinogen is not to act on the corpus carcinosus, and the new method of controlling cancer is to break off its blood supply to make its atrophy death hungry to death.This preparation does not resemble the chemotherapy of today, treating the poisonous disease with poisonous drugs, and the result is patient and cancer destruction of all people good and bad alike, perishes together.Anti-neovascularization medicaments has no side effect, and joins the purpose that the angiogenesis of sufficient dosage opposing cancer own just can reach healing, also can not produce drug dependence by the induced tumor tissue, and also can not produce the reaction of reporting to the leadship after accomplishing a task with other Therapeutic Method.
Initial new vessels inhibitive factor is to extract from the flexible pipe of animal.The flexible pipe of animal does not have blood vessel, the factor that the probability of flexible pipe growth tumor is low to be waited fact to allow people infer to exist anti-new vessels to grow in the flexible pipe, and this factor has the effect of inhibition tumor growth.Breadboard result has proved that this inference is correct.The Volkmann doctor of Harvard University, doctor Pu Ludeng of Columbia University (Dr.John F.Prudden), the Li An of the Massachusetts Institute of Technology (Dr.Anne Lee) and doctor Lang Ge (Dr.Langer R.) and Australian Ge Laigerui. doctor Ha Pu (Dr.Gregory S.Harper) etc. has done very deep basis and clinical research in this respect, has successively delivered a large amount of research papers on " cell ", " science " and journals of high class such as " natures ".
The present new vessels inhibitive factor that studies show that does not exist only in the animal material such as flexible pipe, extensively is present in the vegetable material yet.Inventor herein doctor Qiu Xiaoyi studies show that multiple Chinese herbal medicine contains new vessels and generates inhibitive factor.
Two. the breakthrough of metastatic tumor treatment
Based on there not being a kind of effective method for treatment at present, increasing scientific research institution and scientist throw oneself into and might become current metastasis tumor and treat the research that the anti-new vessels of up-to-date breakthrough generates anticancer field.
At home and abroad, anti-new vessels generates the antineoplastic new drug research and all is in the starting stage, having only a kind of anti-new vessels to generate the antineoplastic monomer medicine at present is that the approval that Chinese " joining a capsule (rg3) " obtain Chinese SFDA the end of the year 2003 is gone on the market in China, rg3 is the important active substances of rare Chinese medicine Radix Ginseng, has tangible antitumaous effect." joining a capsule " is the anti-new vessels generation of the unique production medicine of China's approval, also be that first enters the tumor neogenetic blood vessels inhibitor of clinical practice in the world, to a tumor patient surplus 200 voluntarily separately the pill taker observe, clinical metastasis effective percentage is 60～70%, but its price is very expensive, can not accept for general tumor patient.
Summary of the invention
Technical problem to be solved by this invention is: the natural drug that the prophylaxis of tumours that provides a kind of common tumor patient to accept shifts, and to improve cancer patient's survival rate and quality of life.
The present invention solves its technical problem and adopts following technical scheme:
The natural drug that prophylaxis of tumours provided by the invention shifts is mainly made by following materials based on weight: 40～80 parts of Rhizoma Alismatis, 350～450 parts of Semen Coiciss, 110～130 parts of Rabdosia rubescens, 70～90 parts of Radix Scutellariaes, 430～530 parts of Ganodermas, 40～80 parts in Radix Glycyrrhizae.
The method that the present invention prepares the natural drug of above-mentioned prophylaxis of tumours transfer mainly adopts following step:
(1) extract: Ganoderma is used supercritical CO
2Abstraction technique extracts and separates total Saponin and ganoderan.
(2) decoct: Ganoderma residue and Rhizoma Alismatis, Radix Scutellariae, Semen Coicis, Rabdosia rubescens, Radix Glycyrrhizae five tastes medicine decoct with water in proportion.
(3) decoction liquor is concentrated and extracts extractum, oven dry again through pulverizing 100 mesh sieves, gets the dried powder that soaks of Six-element medical material, and its water content＜7%, bake out temperature are 50～70 ℃.
(4) preparation Chinese Traditional Medicines: with dried powder and ganoderan, the binding agent of soaking of Six-element medical material by making wet granular in the proportioning input mixer granulator, wet granular enters ebullated dryer and carries out drying, put into Multidimensionblender behind the dried particles granulate, carry out always mixing after adding adjuvant, the granule after total the mixing enters granule and deposits between depositing to be checked; Granule after being up to the standards is delivered between the tablet tabletting, through the tablet machine tabletting, gets final product through packing and going into warehouse for finished product after the assay was approved again.
Antineoplastic ultimate principle of the present invention mainly shows following two aspects:
1. histology's operation principle is that anti-new vessels generates anticancer method---the breakthrough that prophylaxis of tumours shifts:
Six kinds of natural plants using in this medicine (damp heart of a lotus seed anticancer tablet) comprise Rhizoma Alismatis, Semen Coicis, Ganoderma, Rabdosia rubescens, Radix Scutellariae and Radix Glycyrrhizae, belong to the natural drug compound preparation according to the Chinese medical theory principles of formulating prescriptions.Through further research, inventor doctor Qiu Xiaoyi finds: Rhizoma Alismatis, Semen Coicis etc. contains the bioactive substance that anti-new vessels generates.Constitute the prescription of this product by Rhizoma Alismatis, Semen Coicis etc., have the biological activity that anti-new vessels generates and anti-tumor neovascularization generates (see and test 1); Also have the function (seeing experiment 2) that suppresses tumor cell proliferation, and toxicity very low (seeing experiment 5 and experiment 6).The bioactive mechanism that anti-tumor neovascularization generates is regulated P53 gene relevant (seeing experiment 4) with the forward of this medicine.This prescription can have two application points to the prevention of metastatic tumor: first application point is that the new vessels that suppresses the primary tumo(u)r periphery generates control tumor cell diffusion (Fig. 1); Among Fig. 1: 1. tumor cell, 2. basement membrane of blood vessel, 3. cellular matrix, 4. new vessels, 5. growth of tumor and transfer, 6. tumor cell, 7. metastatic tumor, 8. new vessels.Second application point is that the new vessels that suppresses the metastatic tumor periphery generates, the growth (Fig. 2) of control metastatic tumor.
2. cytology's operation principle---suppress the propagation of tumor cell:
Studies show that Ganoderma, Radix Scutellariae etc. has been given the effect that " damp heart of a lotus seed anticancer tablet " has the propagation that suppresses tumor cell.
The proliferating cycle of cell, the variation according to its DNA was divided into four processes of carrying out continuously, and they are respectively: (1) G1 phase, the presynthetic phase of also claiming DNA; (2) S phase, i.e. DNA synthesis stage; (3) the G2 phase, also claim DNA post-synthetic phase; (4) the M phase, this phase is the mitotic phase of cell, and is interim at this, intracellular hereditary material--the average lobe of chromosome is 2, and divides equally to two daughter cells with the division of cell.Usually malignant proliferation and aggressive is arranged and extensively the tumor cell of transfer ability call cancerous cell.Suppress the medicine of the propagation of tumor cell, generally be divided into cell cycle specific agents and cell cycle nonspecific agent (CCNSA).Cell cycle specific agents be meant those only to malignant cell in proliferating cycle certain-the phase cell has the medicine of killing action.Cell cycle nonspecific agent (CCNSA) is meant being in the medicine that each phase (G1, S, 32, M) in cell generation cycle or the cell of resting stage (Go phase) all have killing action.
For a long time, China just someone studies and uses the Chinese herbal medicine antitumor, but most studies only focuses on the extraction of clinical research and antineoplastic chemotherapy medicine in the past.Along with the development of modern antitumor technology, also more and more deep to the theoretical research of Chinese herbal medicine antineoplastic, this medicine is exactly to come out in this case, and its main remarkable result is as follows:
One. the principle of traditional inhibition tumor cell proliferation is generated anticancer method with current new antitumor technology-anti-new vessels combine, form this medicine.
This medicine contains multiple anti-tumor bioactivity material, comprise that anti-tumor neovascularization generates bioactive substance, suppresses tumor cell proliferation bioactive substance etc., be primarily aimed at the prevention and the treatment of neoplasm metastasis, its effect mainly shows: test shows to have the function (seeing experiment 3) that prophylaxis of tumours shifts; The new vessels that suppresses tumor generates and tumor cell proliferation, can avoid the generation of metastatic tumor and controls it and develop; The reversing tumor cell dwindles the tumor lump and controls tumor recurrence; Has analgesic effect, immunity-regulating and stimulation hemopoietic function of bone marrow.Wherein, it is significant to suppress tumor cell proliferation, be a kind of breakthrough and the innovation to metastatic tumor prevention and treatment, reciprocity examine result's tumor patient can be used as the medicine of treatment in advance, can become the first-selected alternative medicine of the tumor patient that loses operation and chemicotherapy best opportunity.In addition, the bioactive substance that the anti-new vessels that utilizes modern biotechnology to extract pure natural from Chinese crude drug, natural plant crude drugs generates, optimization of C such as inhibition tumor cell proliferation bioactive substance form, strengthen anti-tumor activity, has hypotoxicity simultaneously, be particularly useful for the patient that those endure cancer pain to the fullest extent, improve the survival rate of cancer patient, have great social significance by the transfer of prophylaxis of tumours.
They are two years old. and the antineoplastic ultimate principle of this medicine innovation is extremely important.The America and Europe, at present the new drug that generates anticancer method research according to anti-new vessels enters having much that the clinical II phase study, such as Angiostatin, Endostatin etc., they all are monomers, new vessels growth function to the inhibition tumor is remarkable, but they do not have tangible inhibited proliferation to tumor cell itself, therefore in I phase and II phase clinical experiment, do not show the long-expected antitumor efficacy of people.On the other hand, Chinese and American-European scientist of past focuses on the extraction of clinical research and antineoplastic chemotherapy medicine etc. mostly to the research of Chinese herbal medicine antineoplastic, the new vessels inhibitory action of tumor is not done deep research.
They are three years old. the more important thing is that the window of having opened a fan research is shifted in the application of the antitumor principle of this innovation for prophylaxis of tumours.
They are four years old. and at present, still being in the primary stage for the prophylaxis of tumours transfer of the natural class of this class and the research of medicine in the world, also is like this in China.The natural compound preparation of antitumor that the prophylaxis of tumours that this medicine is initiated for my company shifts does not also have similar medicine to occur at home, has not only filled up blank, and every technical performance index has reached leading domestic level, and price is relatively cheap.After some time, this medicine brings considerable benefit will for enterprise, society, and market prospect is good.
Description of drawings
Fig. 1 is the first application point sketch map of this medicine prevention metastatic tumor.
Fig. 2 is the second application point sketch map of this medicine prevention metastatic tumor.
Fig. 3 is the active dose positive correlation sketch map that the anti-new vessels of this medicine generates.
Fig. 4 is the Embryo Gallus domesticus model experiment photo that the anti-new vessels of this medicine generates.
Fig. 5 is this medicine toxicity test---cell model (P388) sketch map.
The specific embodiment
The invention will be further described below in conjunction with embodiment.
One. the natural drug that prophylaxis of tumours shifts
Mainly make: 40～80 parts of Rhizoma Alismatis, 350～450 parts of Semen Coiciss, 110～130 parts of Rabdosia rubescens, 70～90 parts of Radix Scutellariaes, 430～530 parts of Ganodermas, 40～80 parts in Radix Glycyrrhizae by following materials based on weight.
Suggestion is made by the raw material of following parts by weight: 480 parts of Ganodermas, 60 parts of Rhizoma Alismatis, 80 parts of Radix Scutellariaes, 400 parts of Semen Coiciss, 120 parts of Rabdosia rubescens, 60 parts in Radix Glycyrrhizae.
Two. the preparation of the natural drug that prophylaxis of tumours shifts
1. extract: Ganoderma is used supercritical CO
2Abstraction technique extracts and separates ganoderan.
2. decoct: Ganoderma residue and Rhizoma Alismatis, Radix Scutellariae, Semen Coicis, Rabdosia rubescens, Radix Glycyrrhizae five tastes medicine decoct with water in proportion.
Each raw materials in part by weight is: 301～371 parts of Ganoderma residues, 50～70 parts of Rhizoma Alismatis, 70～90 parts of Radix Scutellariaes, 350～450 parts of Semen Coiciss, 110～130 parts of Rabdosia rubescens, 50～70 parts in Radix Glycyrrhizae.
3. decoction liquor is concentrated and extracts extractum, dry again, through pulverizing 100 mesh sieves, get the dried powder that soaks of Six-element medical material, its water content＜7%, bake out temperature are 60～70 ℃.
4. preparation Chinese Traditional Medicines: by weight ratio, dried 156 parts in the powder of soaking of Six-element medical material is dropped in the mixer granulator for 40 parts with 144 parts of ganoderans, binder starch and makes wet granular, wet granular enters ebullated dryer and carries out drying, put into Multidimensionblender behind the dried particles granulate, carry out always mixing after adding adjuvant, granule after total the mixing enters granule and deposits between depositing to be checkedly, and adjuvant is a magnesium stearate, and the weight proportion of itself and dried particles is 10 parts, 340 parts; According to national health food technological requirement, the granule after total the mixing that is up to the standards is delivered to tabletting between the tablet tabletting, make tablet, or between capsule is filled, fill the capsule product of making.
Enumerate several examples below according to the present invention's preparation, only for reference.
Example 1: the Ganoderma that will meet standards of pharmacopoeia is used supercritical CO
2Abstraction technique extracts and separates ganoderan; With 336 parts of Ganoderma residues and 60 parts of the Rhizoma Alismatis that meets standards of pharmacopoeia, 80 parts of Radix Scutellariaes, 400 parts of Semen Coiciss, 120 parts of Rabdosia rubescens, 60 parts of five tastes medicines of Radix Glycyrrhizae add suitable quantity of water and decoct; Decoction liquor is concentrated and extracts extractum, dry again, through pulverizing 100 mesh sieves, get the dried powder that soaks of Six-element medical material, its water content＜7%, bake out temperature are 60～70 ℃; Dried powder and ganoderan, the binder starch of soaking of Six-element medical material dropped in the mixer granulator by proportioning (156 parts, 144 parts, 40 parts) and make wet granular, wet granular enters ebullated dryer and carries out drying, put into Multidimensionblender behind the dried particles granulate, carry out always mixing after adding adjuvant magnesium stearate (its weight proportion with dried particles is 10 parts, 340 parts), total granule after mixed enters granule and deposits between depositing to be checked; Granule after being up to the standards is delivered to tabletting between the tablet tabletting according to the national drug technological requirement, makes tablet, or fills between capsule is filled and make capsule.
Embodiment 2.: the Ganoderma that will meet standards of pharmacopoeia is used supercritical CO
2Abstraction technique extracts and separates ganoderan; With 336 parts of Ganoderma residues and 80 parts of the Rhizoma Alismatis that meets standards of pharmacopoeia, 100 parts of Radix Scutellariaes, 400 parts of Semen Coiciss, 100 parts of Rabdosia rubescens, 40 parts of five tastes medicines of Radix Glycyrrhizae add suitable quantity of water and decoct; Following operation is with embodiment 1.
Embodiment 3: the Ganoderma that will meet standards of pharmacopoeia is used supercritical CO
2Abstraction technique extracts and separates ganoderan; With 336 parts of Ganoderma residues and 60 parts of the Rhizoma Alismatis that meets standards of pharmacopoeia, 80 parts of Radix Scutellariaes, 450 parts of Semen Coiciss, 120 parts of Rabdosia rubescens, 40 parts of five tastes medicines of Radix Glycyrrhizae add suitable quantity of water and decoct; Following operation is with embodiment 1.
Embodiment 4: the Ganoderma that will meet standards of pharmacopoeia is used supercritical CO
2Abstraction technique extracts and separates ganoderan; With 301 parts of Ganoderma residues and 70 parts of the Rhizoma Alismatis that meets standards of pharmacopoeia, 90 parts of Radix Scutellariaes, 450 parts of Semen Coiciss, 130 parts of Rabdosia rubescens, 70 parts of five tastes medicines of Radix Glycyrrhizae add suitable quantity of water and decoct; Following operation is with embodiment 1.
Embodiment 5: the Ganoderma that will meet standards of pharmacopoeia is used supercritical CO
2Abstraction technique extracts and separates ganoderan; With 371 parts of Ganoderma residues and 50 parts of the Rhizoma Alismatis that meets standards of pharmacopoeia, 70 parts of Radix Scutellariaes, 350 parts of Semen Coiciss, 110 parts of Rabdosia rubescens, 50 parts of five tastes medicines of Radix Glycyrrhizae add suitable quantity of water and decoct; Following operation is with embodiment 1.
Tablet product in the foregoing description is good fortune board pool, the Kazakhstan heart of a lotus seed anticancer tablet product of our company's development.
Three. experiment
Experiment 1: anti-tumor neovascularization generates experiment
(1) anti-tumor neovascularization generates experiment (animal rabbit corneal tumor vascular pattern): use animal rabbit corneal tumor vascular pattern, detect the function that " damp heart of a lotus seed anticancer tablet " anti-tumor neovascularization generates.
" damp heart of a lotus seed anticancer tablet " anti-new vessels factor forms EVAC (ethylene vinyl acetate copolymer) treatment sheet, is planted in surgical method near the V2 sarcoma of rabbit corneal.
The offside cornea of same rabbit is as contrast.After 20 days, microscope is found: the tumor neogenetic blood vessels that " damp heart of a lotus seed anticancer tablet " anti-new vessels factor obviously suppresses to be excited by the V2 sarcoma forms (87%).
(2) anti-tumor neovascularization generates experiment (Embryo Gallus domesticus model):
Specifically: " damp heart of a lotus seed anticancer tablet " test agent can directly act on the Embryo Gallus domesticus new vessels, by its new vessels growth observation being judged the inhibition or the excitation biological activity of tested reagent.4-6 days Embryo Gallus domesticus new vessels is optimal new vessels model.Tested reagent can directly act on the Embryo Gallus domesticus new vessels, by its new vessels growth observation being judged the inhibition or the excitation biological activity of tested reagent.The characteristics of this living model: this model is a living model, than the entity near human body; Easy, operation easily, stable, repeatability is strong; Can accomplish qualitatively fully, the sxemiquantitative biological activity determination is expressed; Fast, stable, expend lowly, be fit to material screening.The application of this living model in this project: the raw material of screening " damp heart of a lotus seed anticancer tablet ", the biological activity quality of evaluation product.
The result: referring to Fig. 3 and Fig. 4, " damp heart of a lotus seed anticancer tablet " has the activity that anti-new vessels generates.
Experiment 2: tumor cell proliferation suppresses experiment
(1) to the animal transplanting tumor inhibitory action: select the transplanted tumor of two kinds or above mice, rat or rabbit, do the experiment treatment, observe the suppression ratio of solid type tumor.
(2) tumor cell proliferation suppresses experiment (tumor models): three tumor cell lines tentatively having chosen carcinoma of prostate (male's kinds of tumor) and breast carcinoma (women's kinds of tumor) at laboratory experimentize, experimental result shows: " damp heart of a lotus seed anticancer tablet " obviously suppresses the propagation of three tumor cell lines, is in particular in the G2-M phase.Details see attached list 1, table 2, table 3.Table 1: " damp heart of a lotus seed anticancer tablet " obviously suppresses the propagation of prostate PC-3 tumor cell line, shows the G2-M phase.Table 2: " damp heart of a lotus seed anticancer tablet " obviously suppresses the propagation of prostate LNCAP tumor cell line, shows the G2-M phase.Table 3: " damp heart of a lotus seed anticancer tablet " obviously suppresses the propagation of breast carcinoma MCF-7 tumor cell line, shows the G2-M phase.
Test 3. prophylaxis of tumours shift experiments:
Use mouse model, detect the function that " damp heart of a lotus seed anticancer tablet " prophylaxis of tumours shifts.
Concrete grammar is: 10 mices (C57BL/6J, male), the age was 4 weeks.Age gives melanoma cell (B16BL6,5 * 10 by the tail vein when being 5 weeks
4).After 3 days, be divided into two groups at random, wherein one group of percutaneous is injected negative control thing (buffer PBS) down, another group injection " damp heart of a lotus seed anticancer tablet ", treat 14 days continuously after, put to death mice, mouse lung takes out, and through formalin fixed, carries out therapeutic evaluation by anatomic microscope.
Result: in negative control group, the number of pulmonary metastases is 118 ± 15, yet in " damp heart of a lotus seed anticancer tablet " treatment group, the number of pulmonary metastases is 17 ± 8, the P value is less than 0.05 (Student ' s Test-Two-tailed). explanation thus, " damp heart of a lotus seed anticancer tablet " in animal model, has the effect of tangible prevention metastatic tumor.
Test 4. oncogenes regulation and control (Gene Regulation) (P53 gene positive regulation):
In " damp heart of a lotus seed anticancer tablet " experimental therapy group, 60 breast carcinoma mice cases are measured with the method for SABC, find that the P53 protein level obviously improves (63.3%) for 38; Yet, only there are 3 to find that the P53 protein level has raising (5.0%) at matched group; Existing a large amount of activity that experiment showed, enhancing P53 can effectively suppress tumor neovasculature generation (Rastinejadet al., 1989; Bouck, 1990; Good et al., 1990; Dameron et al., 1994a; 1994b; 1994c)
Test 5. acute toxicity test in mice:
Conclusion: two treated animals are not all observed unusual performance, do not see animal poisoning symptom and dead the generation in two weeks, are tried thing LD50 greater than 10g/kg BW, the nontoxic level in true border.
Test 6. toxicity tests---cell model (P388):
Method: the P388 cell is 10cm in size
2Tissue Culture Dish in grow into proper states, culture fluid is DMEM, adds 10% horse serum (GIBCO) and glutaminol, culture environment is 10% CO
2Incubator.Then, cell is transferred to (culture fluid that adds 99 milliliters) in tissue culture's ware, the tested medicine (negative control and tested medicine) that adds 1 milliliter then, dosage is 0.001mg/ml to 0.1mg/ml, toxicity assessment is based on the ATP level of existence cell, and reading instrument is " Wallac Microbeta ".
The result: in the P388 cell toxicity test, " damp heart of a lotus seed anticancer tablet " shows very low toxic action (see figure 5).
Test 7. long term toxicity tests:
With rat is long-term malicious experimental animal, establishes three dosage groups and a matched group, and every grade of 20 rats are adopted administration by gavage administration administration in 2 days in 7 days weekly, the matched group feedwater.High agent group gives more than 50 times of clinical dosage, and middle agent group gives the high dose of suitable pharmacodynamics test, and low agent group gives the effective dose a little more than animal.Administration time is 2-3 a times of clinical trial medication phase.
Be studies show that by above-mentioned laboratory pharmacological toxicology: this product not only shows the biological activity that powerful anti-new vessels generates in Embryo Gallus domesticus new vessels growth inhibited model and white mice animal model, and in tumor models, show powerful inhibition tumor cell proliferation function, the more important thing is that this product shows extremely low toxic and side effects in cell model and white mice animal model experiment.
Show by above-mentioned pharmacological toxicology experimental result: this product prophylaxis of tumours shift safety, effectively, extremely low toxic and side effects arranged.
8. technology maturation degree:
(1) prescription and the dosage form of product have been determined.By breadboard research and development for many years, mathematical statistics methods such as utilization orthogonal test method and fuzzy mathematics optimize " damp heart of a lotus seed anticancer tablet " product prescription, make Tabules, have safe, effective, quality controllable characteristics.
(2) research of chamber pharmacodynamics by experiment, the place of production, source, processing and the process of preparing Chinese medicine etc. of having stipulated Chinese crude drug and natural drug; Physicochemical property and purity to various active ingredients have been done complete researching and analysing, and have finished breadboard extracting method, synthesis technique.
(3) the laboratory pharmacological toxicology studies show that, this product not only shows the biological activity that powerful anti-new vessels generates in Embryo Gallus domesticus new vessels growth inhibited model and white mice animal model, and in tumor models, show powerful inhibition tumor cell proliferation function, the more important thing is that this product shows extremely low toxic and side effects in cell model and white mice animal model experiment.The pharmacological toxicology experimental result shows, this product prophylaxis of tumours shift safety, effectively, extremely low toxic and side effects arranged.Subordinate list
Table 1: the growth of " damp heart of a lotus seed anticancer tablet " inhibition prostate gland cancer cell (PC-3, G2-M).
Table 2: the growth of " damp heart of a lotus seed anticancer tablet " inhibition prostate gland cancer cell (LNCAP, G2-M).
Table 3: the growth of " damp heart of a lotus seed anticancer tablet " " damp heart of a lotus seed anticancer tablet " inhibition breast cancer cell (MCF-7, G2-M).
Table 1
Table 2
Table 3
Claims (5)
1. the natural drug that shifts of a prophylaxis of tumours is characterized in that being made by following materials based on weight:
Rhizoma Alismatis: 40～80 parts,
Semen Coicis: 350～450 parts,
Rabdosia rubescens: 110～130 parts,
Radix Scutellariae: 70～90 parts,
Ganoderma: 430～530 parts,
Radix Glycyrrhizae: 40～80 parts.
2. the natural drug that prophylaxis of tumours according to claim 1 shifts is characterized in that being made by following materials based on weight: 480 parts of Ganodermas, 60 parts of Rhizoma Alismatis, 80 parts of Radix Scutellariaes, 400 parts of Semen Coiciss, 120 parts of Rabdosia rubescens, 60 parts in Radix Glycyrrhizae.
3. the preparation method of the natural drug that shifts of prophylaxis of tumours is characterized in that the preparation method of the natural drug that prophylaxis of tumours shifts mainly adopts following step:
(1) extract: Ganoderma is used supercritical CO
2Abstraction technique extracts and separates ganoderan,
(2) decoct: Ganoderma residue and Rhizoma Alismatis, Radix Scutellariae, Semen Coicis, Rabdosia rubescens, Radix Glycyrrhizae five tastes medicine decoct with water in proportion,
Each raw materials in part by weight is: 301～371 parts of Ganoderma residues, and 50～70 parts of Rhizoma Alismatis, 70～90 parts of Radix Scutellariaes, 350～450 parts of Semen Coiciss, 110～130 parts of Rabdosia rubescens, 50～70 parts in Radix Glycyrrhizae,
(3) decoction liquor is concentrated and extracts extractum, oven dry again through pulverizing 100 mesh sieves, gets the dried powder that soaks of Six-element medical material, and its water content＜7%, bake out temperature are 50～70 ℃,
(4) preparation Chinese Traditional Medicines:
Dried powder and ganoderan, the binding agent of soaking of Six-element medical material dropped in the mixer granulator by proportioning and make wet granular, wet granular enters ebullated dryer and carries out drying, put into Multidimensionblender behind the dried particles granulate, carry out always mixing after adding adjuvant, the granule after total the mixing enters granule and deposits between depositing to be checked; Granule after being up to the standards is delivered between the tablet tabletting, through the tablet machine tabletting, gets final product through packing and going into warehouse for finished product after the assay was approved again.
4. the preparation method of the natural drug that prophylaxis of tumours according to claim 3 shifts is characterized in that: the weight proportion that the Six-element medical material is dried to soak powder and ganoderan, binding agent is 156 parts, 144 parts, 40 parts successively.
5. the preparation method of the natural drug that prophylaxis of tumours according to claim 3 shifts, it is characterized in that: adjuvant is a magnesium stearate, the weight proportion of itself and dried particles is 10 parts, 340 parts.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101205387A CN100446802C (en) | 2005-12-27 | 2005-12-27 | Crude drug for preventing tumor metastasis |
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| CNB2005101205387A CN100446802C (en) | 2005-12-27 | 2005-12-27 | Crude drug for preventing tumor metastasis |
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| CN1990031A CN1990031A (en) | 2007-07-04 |
| CN100446802C true CN100446802C (en) | 2008-12-31 |
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| CN101953839A (en) * | 2010-10-19 | 2011-01-26 | 中国药科大学 | Compound medicinal composition with effect of resisting acute myeloid leukemia |
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| CN102357212B (en) * | 2011-10-12 | 2013-05-29 | 福建华尔康生物科技有限公司 | Compound product obtained through supercritical CO2 extraction, and preparation method thereof |
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| CN1478537A (en) * | 2002-08-26 | 2004-03-03 | 上海中耀生物科技有限公司 | Chinese medicinal composition for anti-cancer and analgesia, its preparation method and its application in the preparation of product and medicine for treating cancer and analgesia |
| CN1478538A (en) * | 2002-08-26 | 2004-03-03 | 上海中耀生物科技有限公司 | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer |
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| CN1478537A (en) * | 2002-08-26 | 2004-03-03 | 上海中耀生物科技有限公司 | Chinese medicinal composition for anti-cancer and analgesia, its preparation method and its application in the preparation of product and medicine for treating cancer and analgesia |
| CN1478538A (en) * | 2002-08-26 | 2004-03-03 | 上海中耀生物科技有限公司 | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer |
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| CN101953839A (en) * | 2010-10-19 | 2011-01-26 | 中国药科大学 | Compound medicinal composition with effect of resisting acute myeloid leukemia |
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