CN101669973B - Biological immunopotentiator composition for treating cancers - Google Patents

Biological immunopotentiator composition for treating cancers Download PDF

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Publication number
CN101669973B
CN101669973B CN2008101070966A CN200810107096A CN101669973B CN 101669973 B CN101669973 B CN 101669973B CN 2008101070966 A CN2008101070966 A CN 2008101070966A CN 200810107096 A CN200810107096 A CN 200810107096A CN 101669973 B CN101669973 B CN 101669973B
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deactivation
bordetella pertussis
injection
salmonella paratyphi
salmonella
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CN101669973A (en
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钟虹光
吕爱平
秋风
卢建中
李丹
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马逸冰
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Abstract

The invention relates to a biological immunopotentiator composition for treating cancers. The composition medicament for treating the cancers mainly comprises 0.5 to 15 billions of inactivated human salmonella typhi, 1 to 10 billions of inactivated bordetella pertussis, and diphtheria toxoid, tetanus toxoid or staphylococcus aureus enterotoxin C. The novel composition is helpful for activating the immune system of a tumor patient, improving the quality of life, and inhibiting tumor growth and metastasis.

Description

A kind of biological immunopotentiator composition for the treatment of cancer
Technical field
The present invention relates to a kind of compositions for the treatment of cancer, especially treat the biological immunopotentiator composition of cancer.The compositions of this treatment cancer mainly contains deactivation people salmonella typhi and deactivation bordetella pertussis; And diphtheria toxoid or tetanus toxoid or Staphylococcal enterotoxin.
Background technology
Annual nearly 2,000,000 people of China suffer from cancer, and 1,500,000 people die from cancer; But also in continuous growth, and be gradually rejuvenation trend.The direct economic loss that cancer causes to China every year exceedes hundred billion yuan (selecting from Beijing Morning 2007/03/31).According to Ministry of Public Health 2007 annual reports, reached 1,800,000 because of the number of tumor mortality to China in 2006, exceeded 300,000 than 2005.Tumorigenic early stage human body is sensation and symptom not, so only have the early discovery of early stage health check-up ability.But clinically at present, the tumour patient more than 80% is treatment to occur after symptom just seeking medical advice, and once making a definite diagnosis, neither early stage, most patient all shifts, and has lost the surgical engine meeting; A lot of tumor patients through operation, also will take chemicotherapy repeatedly to prevent recurrence and shifted.Here it is pursues under the theory of " without tumor existence " countless tumor patients to have to stand spirit and pain constricted and accept undying chemicotherapy animally a lot of doctors, the actual effect tumor has been dwindled, but the whole body Organ Failure appears in patient, and hemocyte is low, the stopped treatment of having to.
Tumor is a kind of systemic disease, should study from the biological characteristics of tumor the clinical treatment of tumor and consideration tumor.Immune system is particularly suitable for removing a small amount of remaining tumor cell, the akinete that especially that radiation and chemotherapy is difficult to kill or tumor stem cell, and this contributed to extend without tumor life cycle.So 1984, Oldham proposed the 4th kind of pattern---the concept of biotherapy of oncotherapy.
The Biotherapeutics of tumor is mainly that the tumor system is killed in the immunity that improves self.Over nearly 10 years, the Biotherapeutics of tumor obtains significant progress, is improving life in patients, reduces relapse rate, and the important function of prevention transfer aspect is more and more approved and payes attention to.Hospital with good conditionsi has carried out the Biotherapeutics project one after another, mainly comprises: the immunomodulator treatment; The treatment of tumor cell tumor vaccine; Adopting property T cell therapy-CIK; The dendritic cell treatment; Hemopoietic Stem Cell Transplantations etc., its purpose is exactly to control the development of tumor by the immunity of enhancing tumor patient.
The above-mentioned Biotherapeutics majority of having carried out clinically can only be higher in condition hospital carry out, and medical expense is high, general patient is difficult to bear, and is difficult to clinically promote.Therefore, finding efficient biological immunopotentiator is one of task of tumor biotherapy.
The inventor, through basic research and clinical practice, thinks and should, from number of ways and many target spots activation body immune system, adjust the immunologic balance of body to the immunization therapy of tumor.Therefore, the present invention adopts the combination of multiple immunobiologic agent.The present composition has stronger activation NKT and the effect of macrophage, thereby suppresses tumor development.
Current many bacterium and toxoid are mainly as vaccine, for prophylactic immunization and anti-infective therapy, although its approach is also by strengthening immune system, but the present invention utilizes polyvalent vaccine, inactivated bacteria and the anatoxic combination selected, give full play to the antineoplastic immune function of body, thereby strengthen the antineoplastic immune function of tumor patient.
Summary of the invention
The object of the present invention is to provide a kind of biological immunopotentiator composition for the treatment of cancer, the compositions of this treatment cancer relates to deactivation people salmonella typhi and deactivation bordetella pertussis; And diphtheria toxoid that can be additional or tetanus toxoid or Staphylococcal enterotoxin be as new combination, have and strengthen body's immunity of tumor patient, suppress tumor growth and prevent the effect of neoplasm metastasis.
Technical scheme of the present invention has following:
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: contain deactivation people salmonella typhi and deactivation bordetella pertussis.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component: the ratio of number of inactivated bacteria of take is deactivation people salmonella typhi 5 hundred million-150 hundred million, deactivation bordetella pertussis 10 hundred million-100 hundred million.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component: 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that also contains following mixing ratio component: in diphtheria toxoid 200Lf-2000Lf or tetanus toxoid 50Lf-500Lf or Staphylococcal enterotoxin 100-5000ng any one or more than one.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component in every 100 ml solns: 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the deactivation Bacillus typhi that deactivation people salmonella typhi is one or more, deactivation Salmonella paratyphi first, deactivation Salmonella paratyphi second.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that also contains following mixing ratio component: polysaccharide 10mg-5g.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: polysaccharide is dextran 0.5-5g or lentinan 50-500mg or ganoderan 50-500mg or polyporusum bellatus 50-500mg.
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: remaining composition is injection normal saline or injection buffer or concentration expressed in percentage by weight 5-10% fat emulsion for injection.
A kind of biological immunopotentiator composition for the treatment of cancer, the material that wherein in every 100 ml solns, contains following mixing ratio component: 500,000,000-5,000,000,000 of 500,000,000-5,000,000,000 of 500,000,000-5,000,000,000 of deactivation Bacillus typhi or deactivation Salmonella paratyphi first or deactivation Salmonella paratyphi second.
The application of above-mentioned biological immunopotentiator composition in the medicine of preparation treatment cancer.
The deactivation people salmonella typhi of indication of the present invention or deactivation bordetella pertussis are that the method or other the conventional ablation methods that according to " Products in China rules ", provide carry out.
Below the part academic term of specialty and corresponding English keywords thereof.
Lf: be anatoxic measurement unit, see " three appendix of Chinese pharmacopoeia 2005 editions.
Indication people salmonella typhi Human Bacillus typhi salmonella of the present invention, comprising: Bacillus typhi Bacillustyphi, the acillus paratyphosus A of Salmonella paratyphi B-grade in the first class, Salmonella paratyphi second Bacillus paratyphosus B.
Bordetella pertussis Bacillus pertussis; Diphtheria toxoid diphtheria toxoid; DT; Tetanus toxoid tetanus toxoid; TT; Staphylococcal enterotoxin is SEC (staphylococcalenterotoxin C, SEC).
Lentinan Lentinus edodes polysaccharide; Ganoderan Ganoderma lucidumpolysaccharide; Polyporusum bellatus polyporus umbellate polysaccharides.
Advantage of the present invention:
Can know deactivation people salmonella typhi bacterium from above analysis of experimental data, the combination of deactivation bordetella pertussis bacterium has had the effect of certain inhibition tumor, its effect that suppresses tumor maintains more than 26% substantially, and, polytype tumor cell is had to inhibitory action; Simultaneously, can significantly improve the life quality of tumor patient, so deactivation people salmonella typhi, the combination of deactivation bordetella pertussis has reasonable oncotherapy and is worth.
Representative as deactivation people salmonella typhi, find one or more deactivation Bacillus typhi in further studying, deactivation Salmonella paratyphi first, deactivation Salmonella paratyphi second has certain contribution to technology, but three kinds of compound deactivation Bacillus typhi, deactivation Salmonella paratyphi first, the better effects if of deactivation Salmonella paratyphi second some.
If in finding to increase diphtheria toxoid or tetanus toxoid or Staphylococcal enterotoxin in further research any one or several usually can be in various degree enhancing deactivation people salmonella typhi, the combination of deactivation bordetella pertussis suppresses the effect of tumor, its suppress the effect of tumor high maintain 60% left and right, even higher, and the kind of inhibition tumor also compares broad-spectrum.
If further in research, finding to increase polysaccharide, enhancing deactivation people salmonella typhi that also can be in various degree, the effect of the inhibition tumor of the combination of deactivation bordetella pertussis etc.Mostly be assosting effect in drug regimen due to polysaccharide, dextran of the present invention, lentinan, ganoderan is a few in numerous polysaccharide, but still can infer and commonly used can be used as medicinal polysaccharose substance and also similar effect can be arranged.
Route of administration of the present invention is mainly subcutaneous injection, and with the water preparation of liquid, Emulsion is main.In common therapeutic scheme, its using method is 0.01-1.5 milliliter/sky, and every three days once, or weekly, treatment cycle is determined according to patient's state of an illness.At water preparation, medicinal normal saline or the injection buffer of therapeutic effect will be arranged in the Emulsion field, or concentration expressed in percentage by weight 5-10% fat emulsion for injection to be made into finished product be general technology.
When normal saline or injection buffer, or the fat emulsion for injection use amount is large, and the effective ingredient in the finished product of configuration is relatively rare, and the dosage of the finished product that treatment or test adopt is just larger.Otherwise normal saline or injection buffer, or the fat emulsion for injection use amount is little, the effective ingredient in the finished product of configuration is relatively dense, and the dosage of the finished product that treatment or test adopt is just less.Injection normal saline of the present invention or injection buffer, or fat emulsion for injection does not affect therapeutic effect in normal ranges.Further do not limit normal saline or injection buffer, or the use amount of fat emulsion for injection can't affect effect of the present invention.
Such as the A scheme can be by 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is made into the finished product of 100 ml solns.
Such as the B scheme can be by 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation effective ingredient of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is made into the finished product of 200 ml solns.
The C scheme is such as can be by 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation effective ingredient of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is made into the finished product of 30 ml solns.
A, B, the C scheme does not have essential distinction aspect treatment, therefore the invention technical scheme is limited in every 100 milliliters to 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio of polysaccharide 0-5g is inappropriate, the proportionate relationship between content that really work or active substance.
Specific embodiment:
The immunopotentiator composition of the treatment cancer below related to obtains in the following manner:
Embodiment 1
By 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation effective ingredient of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 2
By 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation effective ingredient of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 50 milliliters of finished products.
Embodiment 3
By 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 0-2000Lf or tetanus toxoid 0-500Lf or Staphylococcal enterotoxin 0-5000ng, the ratio preparation effective ingredient of polysaccharide 0-5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 200 milliliters of finished products.
Embodiment 4
By 500,000,000 of deactivation people salmonella typhis, 1,000,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 5
By 15,000,000,000 of deactivation people salmonella typhis, 10,000,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 6
By 1,000,000,000 of deactivation people salmonella typhis, 2,000,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 7
By 10,000,000,000 of deactivation people salmonella typhis, 6,000,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 8
By 4,000,000,000 of deactivation people salmonella typhis, 4,000,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 9
By 5,000,000,000 of deactivation people salmonella typhis, 2,500,000,000 of deactivation bordetella pertussis, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 10
Deactivation people salmonella typhi in above embodiment 1-9 is selected the deactivation Bacillus typhi.
Embodiment 11
Deactivation people salmonella typhi in above embodiment 1-9 is selected deactivation Salmonella paratyphi first.
Embodiment 12
Deactivation people salmonella typhi in above embodiment 1-9 is selected deactivation Salmonella paratyphi second.
Embodiment 13
Diphtheria toxoid 2000Lf is added respectively in above-described embodiment 1-12.
Embodiment 14
Diphtheria toxoid 1000Lf is added respectively in above-described embodiment 1-12.
Embodiment 15
Tetanus poison 500Lf is added respectively in above-described embodiment 1-12.
Embodiment 16
Tetanus poison 100Lf is added respectively in above-described embodiment 1-12.
Embodiment 17
Staphylococcal enterotoxin 5000ng is added respectively in above-described embodiment 1-12.
Embodiment 18
Staphylococcal enterotoxin C2 000ng is added respectively in above-described embodiment 1-12.
Embodiment 19
Polysaccharide 5g is added respectively in above-described embodiment 1-12.
Embodiment 20
Polysaccharide 2g is added respectively in above-described embodiment 1-12.
Embodiment 21
Polysaccharide 50mg is added respectively in above-described embodiment 1-12.
Embodiment 22
Polysaccharide 100mg is added respectively in above-described embodiment 1-12.
Embodiment 23
By 1,500,000,000 of deactivation Bacillus typhi, 7,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 100Lf, tetanus toxoid 30Lf, Staphylococcal enterotoxin 100ng, the ratio preparation effective ingredient of lentinan 50mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 24
By 500,000,000 of deactivation Bacillus typhi, 10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 200Lf, tetanus toxoid 50Lf, Staphylococcal enterotoxin 500ng, the ratio preparation effective ingredient of lentinan 500mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 25
By 1,000,000,000 of deactivation Bacillus typhi, 25,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 300Lf, tetanus toxoid 100Lf, Staphylococcal enterotoxin 1000ng, the ratio preparation effective ingredient of lentinan 200mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 26
By 2,000,000,000 of deactivation Bacillus typhi, 50,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 500Lf, tetanus toxoid 200Lf, Staphylococcal enterotoxin C2 500ng, the ratio preparation effective ingredient of ganoderan 50mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 27
By 3,000,000,000 of deactivation Bacillus typhi, 70,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 700Lf, tetanus toxoid 300Lf, Staphylococcal enterotoxin 4000ng, the ratio preparation effective ingredient of ganoderan 500mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 28
By 5,000,000,000 of deactivation Bacillus typhi, 90,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 1000Lf, tetanus toxoid 500Lf, Staphylococcal enterotoxin 5000ng, the ratio preparation effective ingredient of ganoderan 200mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 29
By 7,000,000,000 of deactivation Bacillus typhi, 1,200 hundred million of deactivation bordetella pertussis, diphtheria toxoid 2800Lf, tetanus toxoid 600Lf, Staphylococcal enterotoxin 4500ng, the ratio preparation effective ingredient of dextran 5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 30
By 2,000,000,000 of deactivation Bacillus typhi, 50,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 500Lf, tetanus toxoid 200Lf, Staphylococcal enterotoxin C2 500ng, the ratio preparation effective ingredient of polyporusum bellatus 50mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 31
By 3,000,000,000 of deactivation Bacillus typhi, 70,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 700Lf, tetanus toxoid 300Lf, Staphylococcal enterotoxin 4000ng, the ratio preparation effective ingredient of polyporusum bellatus 500mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 32
By 5,000,000,000 of deactivation Bacillus typhi, 90,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 1000Lf, tetanus toxoid 500Lf, Staphylococcal enterotoxin 5000ng, the ratio preparation effective ingredient of polyporusum bellatus 300mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 33
By 1,000,000,000 of deactivation Bacillus typhi, 500,000,000 of deactivation Salmonella paratyphi first, 500,000,000 of deactivation Salmonella paratyphi second, 2,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 200Lf, tetanus toxoid 30Lf, Staphylococcal enterotoxin 125ng, the ratio preparation effective ingredient of dextran 0.5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 34
By 2,000,000,000 of deactivation Bacillus typhi, 1,500,000,000 of deactivation Salmonella paratyphi first, 2,000,000,000 of deactivation Salmonella paratyphi second, 10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 250Lf, tetanus toxoid 160Lf, Staphylococcal enterotoxin 300ng, the ratio preparation effective ingredient of dextran 5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 35
By 500,000,000 of deactivation Bacillus typhi, 1,000,000,000 of deactivation Salmonella paratyphi first, 200,000,000 of deactivation Salmonella paratyphi second, 25,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 300Lf, tetanus toxoid 100Lf, Staphylococcal enterotoxin 3000ng, the ratio preparation effective ingredient of dextran 1g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 36
By 1,000,000,000 of deactivation Bacillus typhi, 500,000,000 of deactivation Salmonella paratyphi first, 2,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 200Lf, tetanus toxoid 30Lf, Staphylococcal enterotoxin C2 00ng, the ratio preparation effective ingredient of dextran 0.5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 37
1,500,000,000 of deactivation Salmonella paratyphi first, 2,000,000,000 of deactivation Salmonella paratyphi second, 10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 250Lf, tetanus toxoid 200Lf, Staphylococcal enterotoxin 300ng, the ratio preparation effective ingredient of dextran 5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 38
By 4,500,000,000 of deactivation Bacillus typhi, 1,000,000,000 of deactivation Salmonella paratyphi second, 25,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 300Lf, tetanus toxoid 100Lf, Staphylococcal enterotoxin 3000ng, the ratio preparation effective ingredient of dextran 1g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 39
By 1,000,000,000 of deactivation Bacillus typhi, 500,000,000 of deactivation Salmonella paratyphi first, 2,000,000,000 of deactivation bordetella pertussis, tetanus toxoid 30Lf, Staphylococcal enterotoxin C2 00ng, the ratio preparation effective ingredient of dextran 0.5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 40
1,500,000,000 of deactivation Salmonella paratyphi first, 2,000,000,000 of deactivation Salmonella paratyphi second, 10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 250Lf, tetanus toxoid 200Lf, Staphylococcal enterotoxin 300ng, the ratio preparation effective ingredient of dextran 5g, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 41
By 4,500,000,000 of deactivation Bacillus typhi, 1,000,000,000 of deactivation Salmonella paratyphi second, 25,000,000,000 of deactivation bordetella pertussis, Staphylococcal enterotoxin 3000ng, the ratio preparation effective ingredient of dextran 1g, ganoderan 100mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 42
By 4,500,000,000 of deactivation Bacillus typhi, 1,000,000,000 of deactivation Salmonella paratyphi second, 25,000,000,000 of deactivation bordetella pertussis, Staphylococcal enterotoxin 3000ng, the ratio preparation effective ingredient of dextran 2g, lentinan 200mg, ganoderan 10mg, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 43
By 4,500,000,000 of deactivation Bacillus typhi, 1,000,000,000 of deactivation Salmonella paratyphi second, 25,000,000,000 of deactivation bordetella pertussis, Staphylococcal enterotoxin 3000ng, the ratio preparation effective ingredient of life polysaccharide 1g, inject with normal saline or injection buffer, or concentration expressed in percentage by weight 5% fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 44
By 500,000,000 of deactivation Bacillus typhi, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 1,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 45
By 500,000,000 of deactivation Salmonella paratyphi first, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 1,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 46
By 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 1,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 47
By 500,000,000 of deactivation Salmonella paratyphi first, 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 10,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 48
By 500,000,000 of deactivation Salmonella paratyphi first, 500,000,000 of deactivation Bacillus typhi, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 1,000,000,000, inject with normal saline or injection buffer, or concentration expressed in percentage by weight 10% fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 49
By 500,000,000 of deactivation Bacillus typhi, 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 6,000,000,000, inject with normal saline or injection buffer, or concentration expressed in percentage by weight 8% fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 50
By 500,000,000 of deactivation Bacillus typhi, 500,000,000 of deactivation Salmonella paratyphi first, 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 1,000,000,000, inject with normal saline or injection buffer, or concentration expressed in percentage by weight 6% fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 51
By 500,000,000 of deactivation Bacillus typhi, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 10,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 52
By 500,000,000 of deactivation Salmonella paratyphi first, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 10,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 53
By 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 10,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 54
By 500,000,000 of deactivation Bacillus typhi, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 3,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 55
By 500,000,000 of deactivation Salmonella paratyphi first, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 2,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 56
By 500,000,000 of deactivation Salmonella paratyphi second, the ratio preparation effective ingredient that the deactivation bordetella pertussis is 7,000,000,000, inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.
Embodiment 57
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component: the ratio of number of inactivated bacteria of take is deactivation people salmonella typhi 500,000,000, deactivation bordetella pertussis 10,000,000,000.
Embodiment 58
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component: the ratio of number of inactivated bacteria of take is deactivation people salmonella typhi 15,000,000,000, deactivation bordetella pertussis 1,000,000,000.
Embodiment 59
A kind of biological immunopotentiator composition for the treatment of cancer, wherein: the material that contains following mixing ratio component: the ratio of number of inactivated bacteria of take is deactivation people salmonella typhi 3,000,000,000, deactivation bordetella pertussis 7,000,000,000.
Embodiment 60
What in above each embodiment, relate to injects with normal saline or injection buffer with injection, or fat emulsion for injection is mixed with 100 milliliters of finished products.All replace with and inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 180 milliliters of finished products.
Embodiment 61
What in above each embodiment, relate to injects with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.All replace with and inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 60 milliliters of finished products.
Embodiment 62
What in above each embodiment, relate to injects with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.All replace with and inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 120 milliliters of finished products.
Embodiment 60
What in above each embodiment, relate to injects with normal saline or injection buffer, or fat emulsion for injection is mixed with 100 milliliters of finished products.All replace with and inject with normal saline or injection buffer, or fat emulsion for injection is mixed with 40 milliliters of finished products.
Concrete test example
For convenience's sake, adopt the HIS code name to represent the present composition.
Test example one, various dose HIS test the impact of mouse entity tumor tumour inhibiting rate
1, test objective
Investigate suitable dosage range in several representational prescriptions.
2, animal and tumor strain
Laboratory animal: Balb/c mice, body weight 20 ± 1.3g, male and female half and half.Medical courses in general institute Experimental Animal Center provides.Tumor cell line: select S-180 sarcoma, Lewwis pulmonary carcinoma, B16BL6 melanoma, H22 hepatocarcinoma, Ketr-3 people's renal carcinoma, HeLa human cervical carcinoma tumor cell line, source Military Medical Science Institute, Tumour Inst., Chinese Medical Academy, tumour hospital of Peking University.
3, test method
(1) tumour transplatation: get the tumor cells such as eugonic S-180 sarcoma, Lewis lung cancer, BL6 melanoma, H22 hepatocarcinoma, HeLa human cervical carcinoma, MS-070 breast carcinoma and prepare the cell homogenate, cell concentration is adjusted to 2 * 10 7cell/ml, at the left axil of mice subcutaneous vaccination 0.2ml oncocyte homogenate respectively, next day random packet.
(2) test grouping: the mice of tumour transplatation is divided into to 1 at random, lotus tumor matched group, 2, CTX treatment group (positive drug cyclophosphamide group), 3, various dose HIS treatment group: we extract 5 kinds of prescriptions out from the various prescriptions of HIS, be HIS-A, HIS-E, HIS-G, HIS-J, HIS-M, HIS-N is in these 6 kinds of prescription kinds, we respectively get one group and are set as HIS-A1 from prescription scope lower limit, HIS-E1, HIS-G1, HIS-J1, HIS-M1, respectively get one group outside HIS-N1 and high limit and be set as HIS-A5, HIS-E5, HIS-G5, HIS-J5, HIS-M5, HIS-N5, other three dosage are got low in the prescription scope, in, high each three groups (grouping group is in Table 1 in detail), carry out inhibition test research, every treated animal number is 12, male and female half and half.
(3) medication: what mouse tumor was transplanted starts on the 2nd, HIS treatment group subcutaneous injection HIS0.1ml; Lotus tumor matched group subcutaneous injection 0.1ml normal saline, every three days once, 4 times altogether; CTX organizes lumbar injection CTX (cyclophosphamide 30mg/kg), 7 days, after the last administration the 3rd day, put to death mice, dissect animal, take out the tumor strain and weigh, calculate and respectively organize tumour inhibiting rate, tumour inhibiting rate account form: the heavy x100% of the average tumor of tumour inhibiting rate (%)=(the average tumor weight of the average tumor weight-administration of lotus tumor matched group group)/lotus tumor matched group.
4, result of the test
Result of the test, in Table 2, illustrates from table 2 test data:
(1) HIS-A1, HIS-E1, HIS-G1, HIS-J1, HIS-M1, HIS-N1 group are hanged down and have been respectively 29.75%, 26.04%, 29.59%, 27.00%, 28.21%, 27.55% the average tumour inhibiting rate of solid tumor.
(2) HIS-A5, HIS-E5, HIS-G5, HIS-J5, HIS-M5, HIS-N5 group have reached respectively 56.51%, 60.86%, 64.17%, 62.33%, 61.67%, 51.07% to the average tumour inhibiting rate of solid tumor.But we find that in experimental observation these six groups of superelevation limit formula groups go out the animal inertia, hairs, diet minimizing, vomiting etc. are the same with the symptom that the CTX group occurs;
(3) tumour inhibiting rate of getting basic, normal, high three formula groups in the prescription scope is all more than 47%, and relatively tumour inhibiting rate is obvious with ultralow limit group, P<0.01;
(4) CTX group, i.e. chemotherapeutics cyclophosphamide group, tumour inhibiting rate is up to more than 80%, but toxic and side effects is too large, and animal occurs that vomiting, inertia, appetite descend, horripilation, and the phenomena of mortality appear in animal.
(5), from this result of the test explanation, our the prescription scope of design is little to tumour inhibiting rate height and the toxic and side effects of entity tumor, is optimum range.
The HIS grouping group table (test example one) of various dose in six groups, table 1.
Group Composition The prescription ratio
HIS-A1 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 300000000 700,000,000 150Lf
HIS-A2 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 500000000 1,000,000,000 200Lf
HIS-A3 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 3000000000 5,000,000,000 1000Lf
HIS-A4 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 5000000000 10,000,000,000 2000Lf
HIS-A5 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 7000000000 15,000,000,000 2500Lf
HIS-E1 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 300000000 700,000,000 30Lf70ng
HIS-E2 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 500000000 1,000,000,000 30Lf100ng
HIS-E3 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 3000000000 5,000,000,000 250Lf1000ng
HIS-E4 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 500Lf2000ng
HIS-E5 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 7000000000 15,000,000,000 800Lf2500ng
HIS-G1 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 300000000 300,000,000 500,000,000 30Lf70ng
HIS-G2 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 500000000 500,000,000 1,000,000,000 50Lf100ng
HIS-G3 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 3000000000 3,000,000,000 5,000,000,000 250Lf1000ng
HIS-G4 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 5,000,000,000 10,000,000,000 500Lf2000ng
HIS-G5 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 7000000000 7,000,000,000 15,000,000,000 800Lf280ng
HIS-J1 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin 300000000 600,000,000 25Lf100Lf50ng
HIS-J2 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid 500000000 1,000,000,000 50Lf
The diphtheria toxoid Staphylococcal enterotoxin 200Lf100ng
HIS-J3 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin 3000000000 5,000,000,000 25,000,000,000 1000Lf1000ng
HIS-J4 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 500Lf2000Lf200ng
HIS-J5 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin 7000000000 20,000,000,000 800Lf800Lf3000ng
HIS-M1 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid polysaccharide (for example lentinan) 300000000 600,000,000 25Lf100Lf10mg
HIS-M2 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid polysaccharide (for example lentinan) 500000000 1,000,000,000 50Lf200Lf50mg
HIS-M3 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid polysaccharide (for example lentinan) 3000000000 5,000,000,000 250Lf1000Lf100mg
HIS-M4 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid polysaccharide (for example lentinan) 5000000000 10,000,000,000 500Lf2000Lf500mg
HIS-M5 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid polysaccharide (for example lentinan) 7000000000 18,000,000,000 800Lf2800Lf2000mg
HIS-N1 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 300000000 300,000,000 300,000,000 700,000,000
HIS-N2 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 500,000,000 500,000,000 1,000,000,000
HIS-N3 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 3000000000 3,000,000,000 3,000,000,000 5,000,000,000
HIS-N4 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 5000000000 5,000,000,000 5,000,000,000 10,000,000,000
HIS-N5 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 7000000000 7,000,000,000 7,000,000,000 15,000,000,000
The HIS of six groups of various dose of table 2. is to mouse entity tumor tumour inhibiting rate (unit: 100%)
Group S-180 sarcoma tumour inhibiting rate The Lewis lung cancer tumour inhibiting rate B16 melanoma tumour inhibiting rate H22 hepatocarcinoma tumour inhibiting rate Hela cervical cancer tumour inhibiting rate MS070 breast carcinoma tumour inhibiting rate To various tumor grand mean tumour inhibiting rates
Lotus tumor matched group 0 0 0 0 0 0 0
The CTX matched group 89.87 87.89 90.01 86.23 90.45 89.21 88.94△
HIS-A1 20.39 31.16 35.90 32.08 23.90 35.10 29.75
HIS-A2 49.01 49.30 47.45 50.50 47.39 56.01 49.94#
HIS-A3 50.80 60.90 58.09 56.23 50.90 51.10 54.67#
HIS-A4 55.09 50.23 49.90 50.80 49.13 51.98 51.18#
HIS-A5★ 55.30 53.29 65.40 61.01 52.95 51.09 56.51#
HIS-E1 19.49 29.16 26.90 30.90 24.67 25.09 26.04
HIS-E2 60.51 59.30 47.45 62.50 57.39 56.23 57.23#
HIS-E3 62.02 63.90 61.09 60.23 53.90 60.10 60.21#
HIS-E4 65.55 65.25 65.20 60.80 60.13 56.98 62.32#
HIS-E5★ 67.46 65.29 63.40 60.01 55.95 53.09 60.86#
HIS-G1 23.39 31.16 34.90 28.08 23.93 36.10 29.59
HIS-G2 69.01 50.30 60.45 60.55 47.38 56.50 57.37#
HIS-G3 67.83 60.23 63.09 65.23 60.90 55.10 62.06#
HIS-G4 63.09 64.24 61.93 59.83 61.11 59.30 61.58#
HIS-G5★ 65.30 68.29 65.40 66.01 58.95 55.09 64.17#
HIS-J1 29.39 30.24 29.40 26.52 21.40 25.04 27.00
HIS-J2 62.01 55.30 56.45 60.55 50.38 51.50 56.03#
HIS-J3 62.83 60.23 61.09 55.23 61.90 58.10 59.90#
HIS-J4 61.09 65.24 61.95 54.83 64.11 60.30 61.25#
HIS-J5★ 62.30 65.23 65.45 66.35 53.95 60.09 62.33#
HIS-M1 26.49 30.34 25.90 30.24 26.40 30.09 28.21
HIS-M2 62.01 50.30 60.45 49.23 47.38 60.50 54.98#
HIS-M3 65.83 65.23 69.09 66.23 61.90 63.10 65.23#
HIS-M4 64.23 66.22 61.45 67.83 61.23 61.42 63.73#
HIS-M5★ 66.30 68.29 67.40 60.01 57.95 50.09 61.67#
HIS-N1 21.34 29.16 30.30 31.12 23.30 30.13 27.55#
HIS-N2 49.03 38.30 45.45 49.50 46.36 50.01 46.44#
HIS-N3 50.12 49.90 52.12 48.90 50.02 49.29 50.05#
HIS-N4 55.30 52.90 54.23 49.90 51.90 52.14 52.72#
HIS-N5▲ 55.01 50.23 49.09 50.80 51.09 50.23 51.07#
#: compare with the super lower limit group of this group (HIS-A1, HIS-E1, HIS-G1, HIS-J1, HIS-M1, HIS-N1): P<0.01; Tumour inhibiting rate in our dosage range is apparently higher than super lower limit group.
△: CTX cell toxicity medicament cyclophosphamide group and HIS group be P<0.01 relatively, but cellulotoxic side effect is obvious, and mice is movable to be reduced, and appetite descends, and the dead mouse phenomenon, appear in horripilation;
★: be movable minimizing of HIS superelevation limit dosage treated animal, appetite descends, the toxic reactions such as drowsiness, horripilation, vomiting.
▲: HIS-N5 tumour inhibiting rate and HIS-N3, HIS-N4 tumour inhibiting rate difference are little, P > 0.05; But do not improve yet; But indivedual Mus occur that appetite descends, the side effect such as hair Mus setting performance.
Owing to doing widely the work of mouse entity tumor tumour inhibiting rate in comform polygamy side and proportioning, workload is too large, in order effectively to describe the problem and suitably to reduce workload, and our special design and concluded test example one.
By the available result of test example one, be: at the deactivation people salmonella typhi of being shortlisted for, deactivation bordetella pertussis, diphtheria toxoid, tetanus toxoid, golden staphylococcal enterotoxin composition and prescription thereof, will be too low dosage and too high dose rejected.Existence due to test example one, we can think in every 100 milliliters 500,000,000-5,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, good general character has appearred in diphtheria toxoid 200Lf-2000Lf or tetanus toxoid 50Lf-500Lf or Staphylococcal enterotoxin 500-5000ng in above-mentioned scope.This good general character is exactly: dosage is moderate, existing reasonable inhibition, and the animal untoward reaction is less again.
By test example one interpretation of result, we select prescription element dosage range of the present invention suitable, all adopt this dosage range in follow-up test research, and do not select the poor prescription lower than scope dosage of effect and occur side effect higher than scope dosage prescription.
Test example two, different prescription HIS are on mouse entity tumor tumour inhibiting rate impact test
1, animal and tumor strain
Laboratory animal: Balb/c mice, body weight 20 ± 1.3g, male and female half and half.Medical courses in general institute Experimental Animal Center provides.Tumor cell line: select S-180 sarcoma, Lewwis pulmonary carcinoma, B16BL6 melanoma, H22 hepatocarcinoma, Ketr-3 people's renal carcinoma, HeLa human cervical carcinoma tumor cell line, source Military Medical Science Institute, Tumour Inst., Chinese Medical Academy, tumour hospital of Peking University.
2, test method:
(1) tumour transplatation: referring to test example one.
(2) test grouping: by the mice of tumour transplatation be divided at random 1, lotus tumor matched group, 2, CTX treatment group (positive drug cyclophosphamide group), 3, HIS treatment group: according to test example one dose-effect test result analysis, the effect of high, medium and low group that the numbering mantissa of test example one is-4 ,-3 ,-2 correspondences is more or less the same, so as long as we select a prescription dosage, in test example two tests, in the HIS of different groups, select high dose group (referring to grouping group table 3) to carry out the tumour inhibiting rate test of solid tumor, verify again the effectiveness of HIS prescription.
(3) medication: referring to test example one.
3, result of the test
Result of the test is in Table 4, from table 4 result, illustrate, 23 HIS prescriptions have obvious inhibitory action to little s-180 sarcoma, almost surpass the tumour inhibiting rate more than 30%, especially HIS-9, HIS-10, HIS-11, HIS-14, HIS-15, HIS-16 tumor killing effect are better, reach more than 60%.Further this prescription of checking has the effect that suppresses tumor growth.
The different prescription HIS of table 3. treatment group grouping group table (test example two)
Sequence number Group Prescription forms The prescription ratio
1 HIS-1 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 5000000000 10,000,000,000 2000Lf
2 HIS-2 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid 5000000000 10,000,000,000 500Lf
3 HIS-3 Deactivation Salmonella paratyphi second deactivation bordetella pertussis Staphylococcal enterotoxin 5000000000 10,000,000,000 2000ng
4 HIS-4 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 500Lf2000ng
5 HIS-5 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 500Lf2000ng
6 HIS-6 Deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 2000Lf2000ng
7 HIS-7 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis diphtheria toxoid 5000000000 5,000,000,000 10,000,000,000 2000Lf
8 HIS-8 Deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid Staphylococcal enterotoxin 5000000000 5,000,000,000 10,000,000,000 2000Lf2000ng
9 HIS-9 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 5,000,000,000 10,000,000,000 500Lf2000ng
10 HIS-10 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid diphtheria toxoid 5000000000 5,000,000,000 5,000,000,000 10,000,000,000 500Lf2000Lf
11 HIS-11 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin 5000000000 10,000,000,000 500Lf2000Lf2000ng
12 HIS-12 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid dextran 5000000000 10,000,000,000 500Lf2000Lf5g
13 HIS-13 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first 5000000000 10,000,000,000 5,000,000,000
Deactivation Salmonella paratyphi second lentinan 5000000000 400mg
14 HIS-14 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid polyporusum bellatus 5000000000 10,000,000,000 5,000,000,000 5,000,000,000 500Lf2000Lf500mg
15 HIS-15 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid dextran 5000000000 10,000,000,000 5,000,000,000 5,000,000,000 200Lf2000Lf3g
16 HIS-16 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid Staphylococcal enterotoxin lentinan 5000000000 10,000,000,000 200Lf1000Lf1000ng500mg
17 HIS-17 Deactivation Bacillus typhi deactivation bordetella pertussis deactivation Salmonella paratyphi first 2500000000 5,000,000,000 2,500,000,000
18 HIS-18 Deactivation Salmonella paratyphi second deactivation bordetella pertussis 5000000000 10,000,000,000
19 HIS-19 Deactivation Bacillus typhi deactivation bordetella pertussis dextran 5000000000 10,000,000,000 3g
20 HIS-20 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis 5000000000 5,000,000,000 10,000,000,000
21 HIS-21 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis 5000000000 5,000,000,000 10,000,000,000
22 HIS-22 Deactivation Salmonella paratyphi first 5000000000
Deactivation Salmonella paratyphi second deactivation bordetella pertussis 5000000000 10,000,000,000
23 HIS-23 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 5000000000 5,000,000,000 5,000,000,000 10,000,000,000
The HIS of table 4. high dose is to mouse entity tumor tumour inhibiting rate (unit: %)
Group S-180 sarcoma tumour inhibiting rate The Lewis lung cancer tumour inhibiting rate B16 melanoma tumour inhibiting rate H22 hepatocarcinoma tumour inhibiting rate Hela cervical cancer tumour inhibiting rate MS070 breast carcinoma tumour inhibiting rate To various tumor grand mean tumour inhibiting rates
Lotus tumor matched group 0 0 0 0 0 0 0
The CTX matched group 89.87 87.89 90.01 86.23 90.45 89.21 88.94△
HIS-1 49.01 38.30 45.45 41.50 47.39 39.01 43.44
HIS-2 47.80 45.90 50.09 45.23 30.90 41.10 43.50
HIS-3 45.09 36.23 31.90 50.80 48.13 47.98 43.35
HIS-4 47.30 33.29 45.43 38.01 42.95 49.09 42.67
HIS-5 49.51 51.30 47.45 48.50 47.39 46.23 48.39
HIS-6 45.89 47.90 39.90 45.08 39.70 37.20 42.61
HIS-7 50.02 43.90 51.09 40.23 53.90 50.10 48.20
HIS-8 65.55 55.25 60.20 50.80 50.13 56.98 56.48
HIS-9 67.46 65.29 63.40 60.01 65.95 63.09 64.20
HIS-10 69.01 60.30 65.45 61.55 57.38 66.50 63.36
HIS-11 67.83 60.23 65.09 67.23 61.90 65.10 64.56
HIS-12 63.09 64.24 61.93 59.83 61.11 59.30 61.58
HIS-13 45.30 49.29 55.40 46.01 51.95 45.09 48.84
HIS-14 62.01 55.30 56.45 60.55 50.38 51.50 56.03
HIS-15 68.83 65.23 61.09 65.23 61.40 58.10 63.31
HIS-16 67.90 65.29 59.89 67.10 61.23 65.90 63.55
HIS-17 30.29 27.90 31.56 25.09 28.90 30.10 28.97
HIS-18 31.30 35.24 37.95 29.83 34.11 26.30 32.45
HIS-19 32.30 35.23 29.45 26.35 30.95 28.09 30.39
HIS-20 30.01 26.30 37.45 29.23 30.38 27.50 30.14
HIS-21 35.83 32.23 36.09 40.23 41.90 33.10 36.56
HIS-22 34.23 36.22 31.45 37.83 31.23 30.42 33.56
HIS-23 50.20 49.41 51.20 55.90 53.18 49.20 51.51
Test example three, lotus tumor S-180 sarcoma mouse macrophage activity influence is tested
1, tumour transplatation: with reference to test example two.
2, test grouping: the mice of tumour transplatation is divided into to 1 at random, lotus tumor matched group, 2, CTX treatment group (positive drug cyclophosphamide group), 3, HIS treatment group: according to test example one dose-effect test result analysis, the numbering mantissa of test example one is-4,-3, the height of-2 correspondences, in, the effect of low group is more or less the same, so as long as we select a prescription dosage, in this test of test example, in the HIS of different groups, select low dose group (referring to grouping group table 5) to carry out lotus tumor S-180 sarcoma mouse macrophage activity influence is tested, verify again the effectiveness of HIS prescription.
3, medication: with reference to test example one.
4, test method:
After administration after 24 hours, gather peritoneal macrophage the last time:
(1) Turnover of Mouse Peritoneal Macrophages is collected: (" with reference to a kind of foundation that detects the active new method of macrophage phagocytic chicken red blood cell " herding and veterinary's the 37th volume o. 11th in 2005), in order to obtain more macrophage, every mice after administration the 3rd day, the starch meat soup (w/V) of lumbar injection 1mL6%, after 24 hours, mice is put to death in the cervical vertebra dislocation, and with iodine tincture and the 70% ethanol abdominal part of successively sterilizing, again to lumbar injection 4mL physiological salt liquid, knead, the aseptic cortex of cutting open after standing 5min, thrust peritoneum with syringe needle and draw peritoneal fluid in the silication teat glass, with blood counting chamber, count, and calculating macrophage concentration, then by the concentration of normal saline adjustment macrophage, be 5 * 10 6/ mL and 2 * 10 5stand-by after/mL.
(2) chicken red blood cell is collected (herding and veterinary the 37th volume o. 11th " a kind of foundation that detects the active new method of macrophage phagocytic chicken red blood cell " in 2005): the preparation of 25% chicken erythrocyte suspension: under chicken wing, venous blood sampling is stored in A Shi (Alsever) liquid, and the volume ratio of blood and A Shi liquid is 1:4.Before use, first with normal saline washing chicken red blood cell 2 times, each centrifugal supernatant (1000r/min, 5min) of abandoning, finally with the chicken erythrocyte suspension of normal saline preparation 5% (v/V).
(3) phagocytosis test of macrophage, eppendorf manages method: add respectively 5 * 10 6the macrophage suspension of/mL and each 300uL of 5% chicken erythrocyte suspension are in a plurality of aseptic 1.5mL eppendorf pipes, cultivate respectively 45 minutes (5min shakes up once) for 37 ℃, then every pipe is got 300ul and is added on clean coverslip (18mm * 18mm), stick 30min in 37 ℃, PBS (phosphate buffer) with 37 ℃ of preheatings after taking out rinses the chicken red blood cell (the ambassador's macrophage of being sure not to exert oneself is washed out) of not engulfed, put immediately in methanol solution fixedly 3min, with absorbent paper, from absorbing most of methanol, naturally dries at the slide edge, then Giemsa dye liquor dyeing 30min, tap water rinses and goes to dry microscopic examination after unnecessary dye liquor.Each data is similarly the meansigma methods of 10 different mices.
Total macrophage number of the macrophage number of phagocytic percentage (%)=engulf chicken red blood cell/counting * 100%
Total macrophage number of the chicken red blood cell sum/counting of phagocytic index=engulf
5, the macrophage activity measurement result shows, the generation that HIS can stimulating expression of macrophage and the activity of activating macrophage.Macrophage plays a very important role on immunotherapy of tumors, it can directly engulf killing off tumor cells, but also can secrete the indirect killing off tumor cells of many cytokines, and can be used as antigen presenting cell submission antigen, activate the specificity antineoplastic effect.It is relevant with the activating macrophage activity that prompting HIS suppresses tumor growth.The results are shown in Table 6.
The different prescription HIS of table 5. treatment group grouping group table (test example three)
Sequence number Group Prescription forms Prescription ratio 100ml
1 HIS-1 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 500000000 1,000,000,000 200Lf
2 HIS-2 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid 500000000 1,000,000,000 50Lf
3 HIS-3 Deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 1,000,000,000
Staphylococcal enterotoxin 100ng
4 HIS-4 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 500000000 1,000,000,000 50Lf100ng
5 HIS-5 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 500000000 1,000,000,000 50Lf100ng
6 HIS-6 Deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid Staphylococcal enterotoxin 500000000 1,000,000,000 200Lf100ng
7 HIS-7 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis diphtheria toxoid 500000000 500,000,000 1,000,000,000 200Lf
8 HIS-8 Deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid gold staphylococcal enterotoxin 500000000 500,000,000 1,000,000,000 200Lf100
9 HIS-9 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid gold staphylococcal enterotoxin 500000000 500,000,000 1,000,000,000 50Lf100ng
10 HIS-10 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid diphtheria toxoid 500000000 500,000,000 500,000,000 1,000,000,000 50Lf200Lf
11 HIS-11 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid 500000000 10,000,000,000 5,000,000,000 200Lf
The gold staphylococcal enterotoxin 100ng
12 HIS-12 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid dextran 500000000 1,000,000,000 5,000,000,000 200Lf5g
13 HIS-13 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second lentinan 500000000 1,000,000,000 500,000,000 500,000,000 50mg
14 HIS-14 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid polyporusum bellatus 500000000 1,000,000,000 500,000,000 500,000,000 50Lf200Lf100mg
15 HIS-15 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid dextran 500000000 1,000,000,000 500,000,000 500,000,000 50Lf200Lf3g
16 HIS-16 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid gold staphylococcal enterotoxin lentinan 500000000 1,000,000,000 50Lf100Lf100ng50mg
17 HIS-17 Deactivation Bacillus typhi deactivation bordetella pertussis deactivation Salmonella paratyphi first 500000000 1,000,000,000 500,000,000
18 HIS-18 Deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 1,000,000,000
19 HIS-19 The deactivation Bacillus typhi 500000000
Deactivation bordetella pertussis dextran 1000000000 3g
20 HIS-20 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis 500000000 500,000,000 1,000,000,000
21 HIS-21 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 500,000,000 1,000,000,000
22 HIS-22 Deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 500,000,000 1,000,000,000
23 HIS-23 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 500000000 500,000,000 500,000,000 1,000,000,000
Table 6.HIS is to S-180 mouse macrophage activate the phagocytic capacity experimental result
Group Engulf the time (min) Average phagocytic percentage (100%) Average phagocytic index
Lotus tumor matched group 45 10.48±3.95 0.36±0.028
Normal group 45 35.50±7.70 1.06±0.098▲
The CTX group 45 21.10±4.90△ 0.59±0.067△
HIS-1 45 29.91±5.07▲ 0.95±0.111▲
HIS-2 45 35.89±4.09▲ 1.09±0.056▲
HIS-3 45 39.09±4.14▲ 1.23±0.069▲
HIS-4 45 35.23±7.80▲ 1.02±0.108▲
HIS-5 45 36.23±6.90▲ 1.06±0.180▲
HIS-6 45 35.89±4.09▲ 1.09±0.056▲
HIS-7 45 32.29±7.09▲ 0.97±0.056▲
HIS-8 45 35.89±4.09▲ 1.09±0.056▲
HIS-9 45 45.23±7.80▲ 1.59±0.108▲
HIS-10 45 40.22±5.20▲ 1.29±0.108▲
HIS-11 45 47.23±7.80▲ 1.89±0.108▲
HIS-12 45 46.23±6.90▲ 1.36±0.180▲
HIS-13 45 35.89±4.09▲ 1.09±0.056▲
HIS-14 45 46.23±6.90▲ 1.36±0.180▲
HIS-15 45 46.23±6.90▲ 1.36±0.180▲
HIS-16 45 47.23±7.80▲ 1.89±0.108▲
HIS-17 45 21.10±4.90△ 0.59±0.067△
HIS-18 45 19.10±4.90 0.48±0.067△
HIS-19 45 29.91±5.07△ 0.95±0.111▲
HIS-20 45 20.11±4.90△ 0.55±0.067△
HIS-21 45 22.12±2.02△ 0.60±0.067△
HIS-22 45 21.10±4.23△ 0.59±0.067△
HIS-23 45 35.59±4.90▲ 1.07±0.180▲
▲ compare P<0.01 with lotus tumor group; △ and lotus tumor group be P<0.05 relatively
Test example three, to the immune effect of little s-180 sarcoma
1, laboratory animal: referring to test example one.
2, material and cell strain: referring to test example one.
3, test grouping: by the mice of tumour transplatation be divided at random 1, lotus tumor matched group, 2, CTX treatment group (positive drug cyclophosphamide group), 3, HIS treatment group: according to test example one dose-effect test result analysis, the effect of high, medium and low group that the numbering mantissa of test example one is-4 ,-3 ,-2 correspondences is more or less the same, so as long as we select a prescription dosage, in this test of test example, in selecting in the HIS of different groups, dosage group (referring to grouping group table 7) is carried out the Experiment on Function research to lotus tumor S-180 sarcoma mouse immune system.
4, medication: with reference to test example one.
5, test determination method: within the 3rd day after the last administration, respectively organize mice respectively cervical vertebra put to death and to get spleen and carry out following experiment.
(1) acquisition of the mensuration natural killer cells in mice of NK cell killing activity: conventional method prepares splenocyte, and counting is adjusted cell number to 1 * 107/ml, is standby NK cell.Target cell: the L929 cell of cultivating that goes down to posterity is used 0.25% trypsinization 1～2min at the trial, add complete RPMI-1640 and blow and beat gently cell, centrifugal cell is resuspended in containing in the RPMI-1640 of 10% calf serum, adjust cell number to 2 * 105/ml, be the target cell of standby NK cell.The mensuration of NK cytoactive: get the target cell suspension prepared in advance and add in 96 orifice plates, 0.1ml/ hole, then cultivate 1h in incubator, add 0.1ml effector lymphocyte's (making to imitate target ratio 50:1) to every hole, the target cell control wells adds complete 16400.1ml, respectively establish 4 multiple holes, then put into incubator and cultivate 20h, mtt assay detects the NK cytoactive.
Kill rate (%)=(target cell OD value-experimental group OD value)/target cell OD value * 100%.
(2) the conventional preparation of the mensuration of lymphproliferation response 1 * 107/ml splenocyte suspension, add 96 well culture plates, every hole 200 μ l, and the every hole of experimental port adds 50 μ g/ml ConA20 μ l again.Control wells adds culture fluid 20 μ l, and each group is all established parallel hole 3 holes.Cultivate 66～72h in incubator, take out culture plate.Centrifuging and taking supernatant 100 μ l MTT survey the A value, calculate lymphocytic proliferation rate.
(3) lymphocytic proliferation rate (%)=experimental port A value/control wells A value * 100% lymphocyte IL2 induces the preparation with determination of activity IL2 sample: conventional method prepares 1 * 107/ml splenocyte suspension, add ConA5 μ g/ml, be incubated at 24 porocyte culture plates, incubation 24h in 37 ℃ of CO2 incubators; Centrifugal collection supernatant ,-20 ℃ of preservations, be the IL2 testing sample.IL2 detects the preparation of cell: the dislocation of BalB/C mice cervical vertebra is put to death, and conventional method prepares 5 * 106/ml splenocyte suspension, adds ConA2.5 μ g/ml, puts incubation 96h in the Tissue Culture Flask of 25ml.Hank ' the s liquid of 10mg/mla methyl mannoside for cell (a-mm) washes twice, and the adjusting cell concentration is 1 * 106/ml, as the reaction target cell of measuring IL2.The detection of IL2 sample: in 96 porocyte culture plates, every hole adds the IL2 supernatant of reacting cells 0.1ml (1 * 105) and equivalent, and every sample is all established 3 multiple holes.Every hole adds 100mg/ml amm20 μ l, and incubation 48h in the CO2 incubator, by MTT colorimetric method for determining result.
(4) CD3, CD4, CD8 measure: (with reference to Chinese Journal of Immunology, 2002,18 (11): 799-803), get the mouse peripheral blood 100ul of 1 * 107/ml concentration in little centrifuge tube, CD3, the CD4, the CD8 antibody 10ul that add respectively the R-PE labelling, vibration mixes, room temperature, lucifuge are placed PBS washing 2 times for 30min, add again 500ulPBS to mix, after 10min, with flow cytometer FACS Calibur (U.S. BECTON DICKINSON company), detect CD3, CD4, CD8 positive expression rate.
6. experimental result:
(1) HIS group NK cells in mice activity and lymphopoiesis ability are significantly higher than lotus tumor model group mice (P<0.05, P<0.01);
(2) CTX group NK cytoactive and lymphopoiesis ability, significantly lower than lotus tumor model group (P<0.05), illustrate that the CTX chemotherapeutics has the inhibition toxic action to immune system;
(3) HIS group mice IL2 content also is significantly higher than lotus tumor model group and cyclophosphamide group (P<0.01).HIS significantly improves mice CD3, cd4 cell (P<0.01), less on the cd8 cell impact;
(4) HIS significantly improves CD4/CD8 ratio (P<0.01).
HIS can promote the breeder reaction of tumor-bearing mice splenocyte ConA, illustrates that HIS can strengthen cellular immunization.Lymphocyte, under mitogen ConA stimulates, is converted into lymphoblast, and differentiation and proliferation, makes the synthetic increase of intracellular protein and nucleic acid, and the release of the various active factor also increases, and has improved the whole antitumor level of body.HIS has obvious potentiation to the NK cell killing activity, can think that HIS has strengthened the sensitivity that the NK cell stimulates tumor cell, and the NK cytoactive is strengthened.In addition, IL2 can activate the NK cell, but the NK cell direct killing tumor cell after activation also discharges many cytokines as IFN-γ simultaneously, IL-2, and IFN-α, thus enlarge the antitumor spectrum.The results are shown in Table 8.
The different prescription HIS of table 7. treatment group grouping group table (test example three)
Sequence number Group Prescription forms Prescription ratio 100ml
1 HIS-1 Deactivation Bacillus typhi deactivation bordetella pertussis diphtheria toxoid 2500000000 5,000,000,000 1000Lf
2 HIS-2 Deactivation Salmonella paratyphi first deactivation bordetella pertussis tetanus toxoid 2500000000 5,000,000,000 300Lf
3 HIS-3 Deactivation Salmonella paratyphi second deactivation bordetella pertussis Staphylococcal enterotoxin 2500000000 5,000,000,000 100ng
4 HIS-4 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 2500000000 5,000,000,000 300Lf1000ng
5 HIS-5 Deactivation Salmonella paratyphi first 2500000000
Deactivation bordetella pertussis tetanus toxoid Staphylococcal enterotoxin 5000000000 300Lf1000ng
6 HIS-6 Deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid Staphylococcal enterotoxin 2500000000 5,000,000,000 1000Lf1000ng
7 HIS-7 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis diphtheria toxoid 2500000000 2,500,000,000 5,000,000,000 1000Lf
8 HIS-8 Deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis diphtheria toxoid gold staphylococcal enterotoxin 2500000000 2,500,000,000 5,000,000,000 1000Lf1000ng
9 HIS-9 Deactivation Bacillus typhi deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid gold staphylococcal enterotoxin 2500000000 2,500,000,000 5,000,000,000 300Lf1000ng
10 HIS-10 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis tetanus toxoid diphtheria toxoid 2500000000 2,500,000,000 2,500,000,000 5,000,000,000 300Lf1000Lf
11 HIS-11 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid gold staphylococcal enterotoxin 2500000000 5,000,000,000 300Lf1000Lf1000ng
12 HIS-12 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid dextran 5000000000 10,000,000,000 300Lf1000Lf3g
13 HIS-13 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second lentinan 2500000000 5,000,000,000 2,500,000,000 2,500,000,000 300mg
14 HIS-14 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid polyporusum bellatus 2500000000 5,000,000,000 2,500,000,000 2,500,000,000 300Lf2000Lf600mg
15 HIS-15 Deactivation Bacillus typhi whooping cough bacillus deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second tetanus toxoid diphtheria toxoid dextran 5000000000 10,000,000,000 5,000,000,000 5,000,000,000 200Lf2000Lf3g
16 HIS-16 Deactivation Bacillus typhi deactivation bordetella pertussis tetanus toxoid diphtheria toxoid gold staphylococcal enterotoxin lentinan 5000000000 10,000,000,000 20,000,000,000 1000Lf1000ng2000mg
17 HIS-17 Deactivation Bacillus typhi deactivation bordetella pertussis deactivation Salmonella paratyphi first 2500000000 5,000,000,000 2,500,000,000
18 HIS-18 Deactivation Salmonella paratyphi second deactivation bordetella pertussis 2500000000 5,000,000,000
19 HIS-19 Deactivation Bacillus typhi deactivation bordetella pertussis dextran 2500000000 5,000,000,000 3g
20 HIS-20 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation bordetella pertussis 2500000000 2,500,000,000 5,000,000,000
21 HIS-21 The deactivation Bacillus typhi 2500000000
Deactivation Salmonella paratyphi second deactivation bordetella pertussis 2500000000 5,000,000,000
22 HIS-22 Deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 2500000000 2,500,000,000 5,000,000,000
23 HIS-23 Deactivation Bacillus typhi deactivation Salmonella paratyphi first deactivation Salmonella paratyphi second deactivation bordetella pertussis 2500000000 2,500,000,000 2,500,000,000 5,000,000,000
The affect result of the test of table 8.HIS on S-180 sarcoma mouse immune systemic-function
Group NK cell killing activity (100%) Lymphocytic proliferation rate (100%) Induce the active OD of IL-2 670 CD3 CD4 CD8 CD4/CD8
Normal group 78.23±7.21▲ 68.11±7.86▲ 0.268±0.008△ 60.29±5.90▲ 30.90±6.29▲ 18.50±3.56△ 1.670±0.08▲
Lotus tumor matched group 50.47±8.56 44.47±7.28 0.220±0.003 41.09±8.90 20.34±3.90 16.27±3.90 1.25±0.09
The CTX matched group 45.26±6.23# 40.61±7.03# 0.215±0.005 40.67±9.12 22.25±2.97 16.78±6.20 1.30±0.06
HIS-1 59.25±7.12△ 64.35±7.81▲ 0.265±0.008△ 53.38±6.87▲ 31.20±3.90▲ 17.90±3.09 1.74±0.23▲
HIS-2 61.32±4.20▲ 65.28±8.01▲ 0.254±0.002△ 57.89±9.04▲ 30.59±2.40▲ 16.45±5.23 1.86±0.37▲
HIS-3 63.27±4.98▲ 62.67±8.01▲ 0.257±0.008△ 60.50±5.90▲ 31.37±7.10▲ 16.20±4.90 1.93±0.67▲
HIS-4 61.25±9.16▲ 65.25±4.81▲ 0.250±0.002△ 60.45±5.09▲ 30.07±5.90▲ 17.06±5.29 1.79±0.91▲
HIS-5 70.90±9.01▲ 68.32±6.90▲ 0.249±0.003△ 65.54±4.90▲ 34.23±5.74▲ 16.21±2.90 2.11±0.78▲
HIS-6 69.90±5.89▲ 69.23±9.36▲ 0.250±0.005△ 61.90±7.10▲ 30.23±3.42▲ 17.10±3.21 1.77±0.26▲
HIS-7 68.27±4.98▲ 63.67±5.01▲ 0.247±0.009△ 61.50±5.93▲ 30.37±7.13▲ 15.20±4.91 1.93±0.61▲
HIS-8 78.29±2.32▲ 70.52±7.89▲ 0.270±0.004▲ 65.12±7.20▲ 35.20±3.10▲ 17.40±1.09 2.05±0.54▲
HIS-9 80.23±2.34▲ 71.59±8.90▲ 0.283±0.002▲ 67.32±8.20▲ 34.67±2.09▲ 16.90±2.10 2.05±0.14▲
HIS-10 79.09±6.90▲ 69.45±3.53▲ 0.279±0.009▲ 65.78±4.65▲ 35.90±6.78▲ 17.09±2.90 2.10±0.34▲
HIS-11 82.12±3.34▲ 72.30±6.27▲ 0.289±0.003▲ 66.01±5.23▲ 36.67±2.34▲ 17.89±1.09 2.04±0.17▲
HIS-12 81.59±3.45▲ 74.23±7.23▲ 0.294±0.005▲ 68.01±5.98▲ 36.09±3.12▲ 16.90±1.89 2.13±0.13▲
HIS-13 80.20± 72.90± 0.290± 66.90± 36.10± 16.98± 2.13±
6.78▲ 4.90▲ 0.004▲ 2.90▲ 1.23▲ 2.09 0.23▲
HIS-14 79.01±3.90▲ 70.20±3.90▲ 0.287±0.002▲ 65.45±3.45▲ 35.76±3.90▲ 16.09±2.1 2.24±0.17▲
HIS-15 80.20±6.67▲ 70.59±2.12▲ 0.273±0.004▲ 64.32±6.23▲ 34.67±1.90▲ 15.90±3.01 2.18±0.15▲
HIS-16 79.09±7.90▲ 70.45±3.12▲ 0.289±0.003▲ 65.78±7.23▲ 36.90±1.23▲ 16.39±1.98 2.26±0.19▲
HIS-17 53.38±2.56△ 52.30±1.45△ 0.239±0.008△ 50.01±4.90△ 24.67±2.13△ 16.89±2.09 1.46±0.21▲
HIS-18 56.23±4.43△ 58.69±2.12△ 0.249±0.009△ 47.90±7.23△ 25.90±3.09△ 15.43±2.43 1.67±0.13▲
HIS-19 55，26±4.5△ 49.23±5.23△ 0.240±0.004△ 46.30±5.90△ 26.02±2.12△ 16.00±1.98 1.62±0.20▲
HIS-20 57.09±3.43△ 50.23±2.45△ 0.239±0.005△ 45.90±2.45△ 25.90±3.01△ 16.03±2.10 1.61±0.16▲
HIS-21 60.67±4.34△ 56.20±2.45△ 0.250±0.002△ 51.20±7.34△ 28.09±2.13△ 16.90±2.01 1.65±0.19▲
HIS-22 55.18±3.12△ 50.23±4.32△ 0.249±0.005△ 58.23±5.34△ 27.90±1.89△ 15.98±1.09 1.74±0.12▲
HIS-23 56.09±3.43△ 51.23±2.45△ 0.249±0.005△ 45.34±2.45△ 26.90±3.01△ 17.03±2.10 1.57±0.16▲
▲ compare P<0.01 with lotus tumor group; △ and lotus tumor group be P<0.05 relatively; # and lotus tumor group be P<0.05 relatively

Claims (7)

1. a biological immunopotentiator composition for the treatment of cancer, it is characterized in that: the material that contains following mixing ratio component: the ratio of number of inactivated bacteria of take is deactivation people salmonella typhi 500,000,000-15,000,000,000, deactivation bordetella pertussis 1,000,000,000-10,000,000,000, in diphtheria toxoid 200Lf-2000Lf or tetanus toxoid 50Lf-500Lf or Staphylococcal enterotoxin 100-5000ng any one or more than one
2. a biological immunopotentiator composition for the treatment of cancer, it is characterized in that: the material that contains following mixing ratio component in every 100 ml solns: 500,000,000-15,000,000,000 of deactivation people salmonella typhis, 1,000,000,000-10,000,000,000 of deactivation bordetella pertussis, diphtheria toxoid 200Lf-2000Lf or tetanus toxoid 50Lf-500Lf or Staphylococcal enterotoxin 500-5000ng.
3. a kind of biological immunopotentiator composition for the treatment of cancer as claimed in claim 1, is characterized in that: deactivation Bacillus typhi, deactivation Salmonella paratyphi first, deactivation Salmonella paratyphi second that deactivation people salmonella typhi is one or more.
4. a kind of biological immunopotentiator composition for the treatment of cancer as claimed in claim 1, is characterized in that: the material that also contains following mixing ratio component: polysaccharide 10mg-5g.
5. a kind of biological immunopotentiator composition for the treatment of cancer as claimed in claim 4, it is characterized in that: polysaccharide is dextran 0.5-5g or lentinan 50-500mg or ganoderan 50-500mg or polyporusum bellatus 50-500mg.
6. as a kind of biological immunopotentiator composition for the treatment of cancer arbitrarily in claim 2, it is characterized in that: remaining composition is injection normal saline or injection buffer or concentration expressed in percentage by weight 5-10% fat emulsion for injection.
7. the application of biological immunopotentiator composition in the medicine of preparation treatment cancer arbitrarily in claim 1-6.
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