Anti-tumor composite vaccine
Technical field
The present invention relates to antitumor drug, particularly a kind of antineoplastic combination vaccine.
Background technology
Since former US President Nixon in 1971 advised the further investigation tumor treatment in the State of the Union Message since, total funds that the whole world has dropped into tumor research surpassed 2,000 hundred million dollars, publish thesis above 2,000,000 pieces.Said as Nobel laureate Herol Varmus in 1976: " in 30 years, the mankind from almost to the tumor origin cause of formation completely ignorant to having accumulated a large amount of knowledge." development chemotherapeutic and molecular targeted agents get the Green Light with the fastest speed, thrown in market.As if people see the rosy prospect of radical cure tumor.
But the possibility of realization is still can't see in the good hope of people the today after 38 years.Though prolonged than in the past the life cycle of tumor patient, this prolongation is with moon calculating rather than to calculate in year.The tumor that the patient that the minority cure rate is high is greatly improved life cycle often sickness rate is not high, as Hodgkin lymphoma and leukemia.Before 37 years, tumour patient is survived, and the person accounts for 50% more than 5 years and 5 years in sum, and this numeral only brings up to 63% now, and this percentage ratio that slightly improves is mainly given the credit to the progress of early diagnosis.Seattle, u.s.a tumor research center a biometrics expert point out, if several big tumors such as pulmonary carcinoma, intestinal cancer, breast carcinoma and carcinoma of prostate by the different phase of making a definite diagnosis, whether promptly spread and the diffusion analysis by cancerous cell, progressive stage is the almost not variation of 5 years survival rates of middle and advanced stage tumor patient so in recent decades.
Progressive stage tumor patient comprise tumor can not the excision person, find in the operation cancerous protuberance transferrer, to chemotherapy, radiotherapy nonresponder, or tumor recurrence person.How to prolong these survival time of patients, be present tumor research most important also be the most difficult problem.
1, chemotherapy can not effectively prolong patient's life cycle
The traditional treatment of tumor comprises operation, chemotherapy and radiation.The above two are topical therapeutics, unless the metastasis limitation generally can not be eliminated the dissemination pathological changes.To the progressive stage tumor, chemotherapy is at present main treatment means as whole body therapeutic.
Clinical report shows that chemotherapy is difficult to effectively prolong patient's life.For example: Park etc. use a kind of 5-fluorouracil (5-FU) derivating agent S1 and mitomycin (MMC) treatment 42 routine progressivity gastric cancer, and 21% has objective reaction, keeps 3.4 months, and meta gets nowhere 3.4 months life cycles, total August life cycle.Oxaliplatin (oxaliplatin) associating 5-FU is used in reports such as Huang and tetrahydrofolic acid is treated 55 routine progressivity gastric cancer, and 5.4% obtains complete reaction, 36.4% partial reaction, and 34.5% is stable, and meta is total 10.8 months life cycles to making progress 5.6 months life cycles.Pennathur reports that the 70 routine local progressivity esophageal carcinoma accept cisplatin (CDDP), 5-FU and paclitaxel (PTX) 2-3 cycle, does the esophagus excision then, adjuvant chemotherapy again, median survival interval 27.4 months.14 examples are in the still existence nothing recurrence during 79 months of meta follow-up period.
Fruscio etc. have carried out the II phase and have studied, 280 routine ovarian cancers are accepted CDDP, paclitaxel, epirubicin (CEP) or CDDP, PTX, different ring phosphorus vinegar amine (CIP), the result shows that two groups of patient's median survival interval were respectively 51 months and 65 months, and survival rate was respectively 43% and 50% in 5 years.
The treatment of progressivity cancer of pancreas is main at present to rely on chemotherapy or/and radiotherapy.The result of each family's report is not the same, and meta does not have 3~10 months progression of disease phases, median survival interval 7~16 months, and most reports are less than 10 months; The objective response rate 22%~40% of tumor; 1 annual survival rate 20%~78%, majority is less than 60%.
2, new antitumor drug fails to improve therapeutic effect
Two Italian pharmacologisies were to 1995~2000 years 12 kinds of efficacy of new drug in the Europe listing, compare with corresponding approval therapy, do not find that these new drugs have the superior part of any substance to patient's survival rate, quality of life does not improve yet, safety does not improve yet, and the price of this medicine rises significantly, expensive 350 times than " old medicine " of wherein a kind of new drugs.
3, molecular targeted agents still can not effectively prolong patient's life
Along with development of molecular biology, the targeted drug that differs at the mechanism of different target position is come out one after another and is applied to clinical.Can these medicines prolong tumor patient life cycle progressive stage on earth, still can't see the possibility of success at present.
In the molecular targeted treatment of parenchyma, only (imatinib gleevic) can effectively prolong gastrointestinal stromal tumor patient life in late period to imatinib.During the II phase that Nishida etc. carry out studied, 74 routine patients accepted this medicine 400~600mg/d, and meta gets nowhere 96 weeks of life cycle, estimates 3 years survival rates 73.6%, and other molecular targeted agents all can not effectively prolong patient's life cycle.
4, immunization therapy might bring the patient to prolong life cycle
The method of immunotherapy of tumors is a lot, as cytokine, tumor vaccine, adoptive immunity effector lymphocyte etc.The effective tumor of immunization therapy mainly contains melanoma, renal carcinoma, lymphoma etc.Report such as Tauceri IV phase melanoma patients, the auxiliary treatment person of back based on immunization therapy DC cell, tumor infiltrating lymphocyte (TIL) undergos surgery, mean survival time (MST) is 62.7 months, median survival interval 50.9 months, 42.4 and 16 months of being longer than surgery alone person life cycle respectively.Khammari etc. to 88 routine III phase melanoma patients carried out to the time followed up a case by regular visits in 10 years, find that TIL adds interleukin II and can obviously prolong patient's life cycle.Application such as Mitchell self melanoma is melted thing injection and is added low dosage a interferon or Large dosage interferon injection, treats melanoma behind the 604 routine III stage operations, and meta gets nowhere 59~50 months life cycles.It is that main immunotherapy is treated 2 routine recurrent metastasis melanin tumors that the inventor once used the DC cell, is respectively life cycle phase that gets nowhere 8 years and 4 years.
Vose etc. give autologous stem cell transplantation to 248 routine recurrent non Hodgkin lymphomas, and the total and survival rate that gets nowhere was respectively 63% and 44% in 5 years, was higher than the result of general reported literature.
Immunotherapy does not still have the report of serial randomized prospective research at present to the curative effect of progressivity entity tumor.Collect a kind of what is called " Issels therapeutic scheme " from network, mainly comprised immune response modifier (interferon, other cytokines), monoclonal antibody and tumor vaccine.The tumor of using this scheme treatment comprises various adenocarcinoma, osteocarcinoma, cerebroma, breast carcinoma, pulmonary carcinoma, colon cancer, gastric cancer, uterus carcinoma, sarcoma etc., enumerates nearly hundred routine late tumor patients altogether, survives for many years and even many decades in the treatment back.Many systems are by the professor of internal medicine of hospital of imperial family of London university, the preceding consultant JohnAnderson of WHO oncology record in the case of these long term survivals.
Tumor vaccine has been proved to be and can have caused that tumor shrinks back, and prolongs lotus tumor person life cycle.The inventor has followed up a case by regular visits to for 1991~nineteen ninety-five recently and has used various progressivity tumor patient 53 examples of bacterial vaccine treatment.Therapeutic Method is a mixed cell vaccine subcutaneous injection, and is weekly, continuous 3 week back rests 10 days, and duplicate injection again, the state of an illness progressively prolongs the gap phase after improving, as far as possible prolonged application.The patient who receives treatment is one of following person: tumor can not the excision person, find neoplasm metastasis or diffusion person in the operation, to radiotherapy/chemotherapy nonresponder, or the recurrent tumor person.Follow up a case by regular visits to calendar year 2001, be mainly progressivity gastric cancer, carcinoma of gastric cardia, colon cancer, pulmonary carcinoma, breast carcinoma etc.All patients all survived more than 5 years.
Main application mix bacterial vaccine of above-mentioned case and viral vaccine are treated.Proved already that bacillus calmette-guerin vaccine all had certain curative effect to many cancerous protuberances such as pulmonary carcinoma, melanoma, lymphoma etc.; Intravesical perfusion bacillus calmette-guerin vaccine is the standard method of the representative bladder cancer of treatment; Measles has the cancerous cell of melting effect, infers that its vaccine has anticancer effect.
In anti-tumor biological therapy field, bias toward specific immunotherapy for a long time, as LAK, the TIL etc. based on the T cell, the monoclonal antibody of B cell and conjugate thereof are constantly used and are developed.Immunomodulator with the non-different in nature active immunotherapy of activating macrophage just comes into one's own recently, in fact, at home and abroad is a main most widely used class always.This therapy also belongs to this category.Ancient Coley ' s polyvalent vaccine (MBV) is applied to clinically by rising in 1893, still has report (Med oncol﹠amp the nineties; Tumor phamacol therapy).Be representative the sixties with BCG, occurs OK-432 in succession, CP....It comprises microorganism (antibacterial thalline and relevant composition, virus, fungus), vegetable polysaccharides and synthetic high and low molecular compound.All there is such launch in each state, through the NCI contrast test, thinks that the OK-432 effect of Japan is the strongest, clinically as three big conventional therapy complementary therapies.
In current oncotherapy field, for existing shift or conventional therapy after the late tumor that recurs, treat very difficultly, chemotherapy remains main treatment means, but for most of tumors, is difficult to effectively prolong patient's life.Immunization therapy has been considered to prolong the late tumor patient important means of life cycle.With cytokine and adoptive immunity cell is the immunotherapy of representative, and demonstration can make the tumor patient of some conventional therapy failures or recurrence obtain existence and be benefited.But these methods are often made complexity, cost an arm and a leg, for example dendritic cell vaccine and cytokine induced kill cell, needs extraction patient hemocyte is cultivated and is induced, strict laboratory condition must be arranged, and agents useful for same is very expensive, so that is difficult to be born by general patient.The more important thing is that the effect that existing immunotherapy produced is often limited, the erworbene Krankenheit remission rate only is 10%~20%, and the existence benefit factor is no more than 20%.
Summary of the invention
In order to overcome the shortcoming of above-mentioned prior art, task of the present invention provides a kind of anti-tumor composite vaccine, and it takes to strengthen the measure of human body anti-tumor capacity by immunization therapy, but the inducing cancer cell dormancy allows long-term disease free survival of patient or band tumor survive.
Technical solution of the present invention is as follows:
A kind of anti-tumor composite vaccine, it contains lipomul, it also contains DPT vaccine, Measles Vaccine, antityphoid vaccine, staphylococcus aureus vaccine, paratyphoid fever vaccine, paratyphoid fever vaccine and adjuvant, described adjuvant comprises microorganism A, lecithin, Tween 80, span 20 and injection Oleum Glycines, described lipomul is the infatmul agent, the content of specific components in weight percent as follows:
DPT vaccine 8%~9%, Measles Vaccine 8%~9%, antityphoid vaccine 8%~9%, staphylococcus aureus vaccine 8%~9%, paratyphoid fever vaccine 8%~9%, paratyphoid fever vaccine 8%~9%, adjuvant 5%~10%, infatmul agent 41%~47%.
The present invention takes following further technical measures:
First embodiment of the prescription of described anti-tumor composite vaccine, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 10%, infatmul agent 42%.
Second embodiment of the prescription of described anti-tumor composite vaccine, its constituent content is by weight percentage: DPT vaccine 9%, Measles Vaccine 9%, antityphoid vaccine 9%, staphylococcus aureus vaccine 9%, paratyphoid fever vaccine 9%, paratyphoid fever vaccine 9%, adjuvant 5%, infatmul agent 41%.
The 3rd embodiment of the prescription of described anti-tumor composite vaccine, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 5%, infatmul agent 47%.
The 4th embodiment of the prescription of described anti-tumor composite vaccine, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 7%, infatmul agent 45%.
Described anti-tumor composite vaccine also contains the OK432 vaccine, and OK432 vaccine content accounts for 2% of whole constituent contents.
Described anti-tumor composite vaccine also contains the coryne bacterium parvum vaccine, and the coryne bacterium parvum vaccine contg accounts for 2% of whole constituent contents.
Described anti-tumor composite vaccine also contains pseudomonas aeruginosa vaccine, and pseudomonas aeruginosa vaccine content accounts for 2% of whole constituent contents.
Described anti-tumor composite vaccine also contains the Listerella vaccine, and the Listerella vaccine contg accounts for 2% of whole constituent contents.
Described anti-tumor composite vaccine also contains the Bacillus proteus vaccine, and the Bacillus proteus vaccine contg accounts for 2% of whole constituent contents.
The present invention is a kind of anti-tumor composite vaccine that is made through special formulation by multiple commercially available microorganism vaccine.Combination vaccine of the present invention has following characteristics:
1, the equal avirulence of each composition, the approval clinical practice of national already pharmaceutical control and administration department, therefore fool proof.
2, used various vaccines prove the effect of excitating organism immunologic function, inhibition tumor growth all by research both at home and abroad.
3, multiple vaccine is mixed and made into combination vaccine, can excites or induce different immunocytes or cytokine, thereby synthetically act on tumor, produce synergy.
4, vaccine that has such as Listerella composition have carrier function, can infect the occupational antigen presenting cell natively, excite I type and II type angtigen presentation approach, induce the reaction of strong natural sex and adaptive immunity.
5, the non-vaccine composition can increase the dispersivity and the stability of vaccine molecule in this combination vaccine, promotes the vaccine molecule infiltration to go into the effector lymphocyte, and what have itself promptly has the effect of inducing body's immunity.
For the progressivity tumor patient, especially once accepted the conventional therapy person, take chemotherapy, what don't work is " old medicine " or " new drug ", all can not prolong patient's life cycle; The patient prolonged life cycle after some case report was presented at combined chemotherapy, may be in good condition relevant with patient's fundamental immunity; Molecular targeted treatment is the new way of current oncotherapy, but still can not make a breakthrough on life cycle the prolongation patient; And immunization therapy has been considered to the fourth-largest therapy of tumor, and method is a lot of.
Closely during the last ten years, along with increase to immunity monitoring and tumour immunity mechanism understanding, a kind of new type anticancer strategy and technology---strengthen the immunotherapy of the anticancer cellular immune function of body, come out and obtain fast development.The famous cancer expert of the U.S., the chief editor Herman kattlove of ACS say: " immunotherapy may be unique carcinogenic in the method at fatal position." " under the situation that does not have new drug to come out, chemotherapy (to the patient) is a dead zone ... ".The Ronald doctor of Stanford University says that " stem-winding is that we see that (immunization therapy) becomes the modern weapons of anticancer war.”
Using anti-tumor composite vaccine of the present invention, then is a kind of measure that strengthens the human body anti-tumor capacity, but the inducing cancer cell dormancy allows long-term disease free survival of patient or band tumor survive.
By anti-tumor composite vaccine of the present invention, to make according to prescription, manufacture method is simple, and antitumor spectra is wide, and safety non-toxic does not almost have side reaction, and if can develop becomes new drug, its low price, the society and economy meaning that especially it had will be immeasurable.
The specific embodiment
By the prescription of anti-tumor composite vaccine of the present invention, wherein main formula contains lipomul, DPT vaccine, Measles Vaccine, antityphoid vaccine, staphylococcus aureus vaccine, paratyphoid fever vaccine and paratyphoid fever vaccine, and secondary prescription contains adjuvant.Adjuvant comprises microorganism A, lecithin, Tween 80, span 20 and injection Oleum Glycines.Lipomul is the infatmul agent.
The content of specific components in weight percent as follows of this combination vaccine prescription:
DPT vaccine 8%~9%, Measles Vaccine 8%~9%, antityphoid vaccine 8%~9%, staphylococcus aureus vaccine 8%~9%, paratyphoid fever vaccine 8%~9%, paratyphoid fever vaccine 8%~9%, adjuvant 5%~10%, infatmul agent 41%~47%.
First Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 10%, infatmul agent 42%.
Second Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 9%, Measles Vaccine 9%, antityphoid vaccine 9%, staphylococcus aureus vaccine 9%, paratyphoid fever vaccine 9%, paratyphoid fever vaccine 9%, adjuvant 5%, infatmul agent 41%.
The 3rd Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 5%, infatmul agent 47%.
The 4th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 7%, infatmul agent 45%.
The 5th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, adjuvant 9%, infatmul agent 43%.
Anti-tumor composite vaccine of the present invention can also contain the OK432 vaccine, and OK432 vaccine content accounts for 2% of whole constituent contents.If added OK432 vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain the coryne bacterium parvum vaccine, and the coryne bacterium parvum vaccine contg accounts for 2% of whole constituent contents.If added coryne bacterium parvum vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain pseudomonas aeruginosa vaccine, and pseudomonas aeruginosa vaccine content accounts for 2% of whole constituent contents.If added pseudomonas aeruginosa vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain the Listerella vaccine, and the Listerella vaccine contg accounts for 2% of whole constituent contents.If added Listerella vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain the Bacillus proteus vaccine, and the Bacillus proteus vaccine contg accounts for 2% of whole constituent contents.If added Listerella vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain bronchitis vaccine, and bronchitis vaccine content accounts for 2% of whole constituent contents.If added bronchitis vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
Anti-tumor composite vaccine of the present invention can also contain urine sense vaccine, and urine sense vaccine content accounts for 2% of whole constituent contents.If added urine sense vaccine, the content of then corresponding minimizing adjuvant or infatmul agent, the content of perhaps corresponding minimizing main formula.
The 6th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, OK432 vaccine 2%, adjuvant 7%, infatmul agent 43%.
The 7th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, coryne bacterium parvum vaccine 2%, adjuvant 8%, infatmul agent 42%.
The 8th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, pseudomonas aeruginosa vaccine 2%, adjuvant 6%, infatmul agent 44%.
The 9th Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, Listerella vaccine 2%, adjuvant 5%, infatmul agent 45%.
The tenth Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, OK432 vaccine 2%, Listerella vaccine 2%, adjuvant 5%, infatmul agent 43%.
The 11 Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, OK432 vaccine 2%, pseudomonas aeruginosa vaccine 2%, Listerella vaccine 2%, adjuvant 5%, infatmul agent 41%.
The 12 Example formulations by anti-tumor composite vaccine prescription making of the present invention, its constituent content is by weight percentage: DPT vaccine 8%, Measles Vaccine 8%, antityphoid vaccine 8%, staphylococcus aureus vaccine 8%, paratyphoid fever vaccine 8%, paratyphoid fever vaccine 8%, pseudomonas aeruginosa vaccine 2%, Listerella vaccine 2%, adjuvant 6%, infatmul agent 42%.
Experiment showed, that application combination vaccine 0.1ml/20g of the present invention can be to the effect of animal toxigenicity, this dosage is equivalent to clinical thousands of times with dosage, shows that it is fool proof.
Experimentation shows that the injection of this combination vaccine has following effect: (1) increases the weight of animal immune organ spleen, promotes spleen germinal center propagation; (2) improve the body macrophage activity; (3) raise lymphocyte CD 4 activity, downward modulation CD8 activity, the generation of the promotion or the inducing cell factor such as IFN, IL-2, TNF.
Experimentation also shows, to experimental tumor, this combination vaccine has the effect of the tumor growth of inhibition, to Hepar Mus cancer, Mus S180 sarcoma, Mus bladder cancer and the melanomatous inhibitory rate of Mus B16 more than 50%; HAC ehrlich ascites carcinoma and Ehrlich ehrlich ascites carcinoma had its nucleus formation of prevention.
Clinical practice and animal experiment through the several years studies confirm that anti-tumor composite vaccine of the present invention has certain curative effect, the energy antitumor, and anti-intractable chronic infection, antiimmune disorder and low, anti-some metabolic disease comprises atherosclerosis.Aspect oncotherapy, anti-tumor composite vaccine of the present invention can and be used with three big conventional treatments, energy potentiation, attenuation, be particularly useful for not having indication or invalid progressivity tumor through three big conventional therapies, its anticarcinogenic effect is comparatively obvious and comprehensive, except the dispersing tumor effect, improve KPS in addition, rise effects such as white, analgesia and anti-recurrence.
Certainly, those skilled in the art in the present technique field will be appreciated that, above-mentioned all embodiment are used for illustrating the present invention, and be not as limitation of the invention, as long as in connotation scope of the present invention, all will drop in the scope of claim of the present invention conversion, the modification of the foregoing description.