CN1465353A - Becterin of Serratia marcescens for curing - Google Patents
Becterin of Serratia marcescens for curing Download PDFInfo
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- CN1465353A CN1465353A CNA021119961A CN02111996A CN1465353A CN 1465353 A CN1465353 A CN 1465353A CN A021119961 A CNA021119961 A CN A021119961A CN 02111996 A CN02111996 A CN 02111996A CN 1465353 A CN1465353 A CN 1465353A
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Abstract
The present invention relates to a Serratia marcescens bacterine. It is a strain having the action of resisting tumor. Said invented Serratia marcescens bacterine mainly is used for resisting tumor and regulating immunological function, so that it can obtain good therapeutic effect for curing some diseases related to immunological function, it also has the action of resisting anaphylaxis.
Description
The present invention relates to medicine with the serratia marcescens preparation and uses thereof.
The separation and purification from the cockroach internal organs of this research department goes out a strain serratia marcescens S311 strain.This bacterial strain is a gram negative bacilli, and whole body flagellum is dynamic, no pod membrane and brood cell, this bacterium is under general aerobic condition, and well-grown on 37 ℃ of ordinary culture mediums is on the plain agar flat board, bacterium colony is smooth moistening, projection, neat in edge, rounded, biochemical reaction: energy glucose fermentation, sucrose, mannitol, amygdalin, produce not aerogenesis of acid.Azymic rhamnose, arabinose, close disaccharide.Can produce the outer deoxyribonuclease of born of the same parents.Bacterium numbering: CGMCCNO.0744, classification name: serratia marcescens Serratia marcescens.
Serratia marcescens has antitumor action, adopts the separating animal's intestinal bacteria, and the antibacterial that tumor-inhibiting action is arranged is relatively screened discovery, and serratia marcescens has the effect of direct killing tumor cell in the intestinal.Vaccine after the serratia marcescens deactivation still maintains medium direct cell toxicant.Serratia marcescens Seedling or crude extract (cell membranous structure and ribosome thereof etc.) can be made the antineoplastic immunomodulator.Comprise with the medicine of serratia marcescens preparation or the therapeutic domain of immune formulation: antitumor, treatment cancerous ascites pleural fluid, immunomodulating, auxiliary chemicotherapy treatment, leukocyte increasing, treatment psoriasis, treatment condyloma acuminatum, treatment lupus erythematosus heating and skin erythema, treatment behcet's syndrome.
1. the serratia marcescens Seedling is good immune inducing agent
1.1 activation to spleen
The S311 vaccine mainly has immunologic enhancement to reticuloendothelial system, can cause the enlargement of immune mouse spleen.The disposable administration 25,000,000,000/kg of mouse peritoneal (8mg/kg) played spleen index in 3 days and begins to increase, and reached summit, (seeing Table 1) in 7-14 days.
The relation of table 1 S311 vaccine immunization natural law and spleen index
Heavy (mg)/body weight (g) spleen index of immunity natural law spleen P
The matched group experimental group
3 5.75±0.53 8.52±0.75 1.48 ＜0.05
7 3.87±0.42 8.05±0.63 2.08 ＜0.05
10 4.75±0.67 9.35±0.88 1.97 ＜0.05
14 4.08±0.58 6.65±0.55 1.63 ＜0.05
20 4.50±0.68 6.22±0.72 1.38 ＜0.05
1.1.2 effect to macrophage phagocytic function
The S311 vaccine can strengthen macrophage phagocytosis of mice.By 12,500,000,000/kg (4mg)/kg body weight, abdominal cavity single administration, C after 7 days
57The ability that the BL/6 Turnover of Mouse Peritoneal Macrophages is engulfed dimethyl diaminophenazine chloride increases by 6.31 times, relatively is significant differences (P＜0.01) with matched group, and the relation of different dosing dosage and phagocytic index sees Table 2.
Table 2 S311 is to C
57The drug dose number of animals peritoneal macrophage that influences of BL/6 macrophage phagocytosis of mice is counted cytophagy dosage phagocytic index
Hundred million/kg (only) * 10
4/ ml ug/5 * 10
4Cell NS 0.5ml 10 102.0 ± 25.3 0.118 ± 0.196S311 31.25 10 120.0 ± 27.8 0.370 ± 0.175
*3.14S311 62.5 10 143.5 ± 32.1 0.540 ± 0.196
*4.58S311 125 10 178.1 ± 29.9 0.745 ± 0.177
* *6.31S311 250 10 168.0 ± 25.1 0.660 ± 0.180
* *5.59
Note: compare with matched group
*P＜0.05
* *P＜0.01
1.2 the effect of induced tumor necrosin (TNF)
The S311 vaccine can external evoked mouse macrophage TNF-α generation.At C
57Add 5 * 10 in the BL/6 Turnover of Mouse Peritoneal Macrophages culture supernatant
6Bacterium number/ml induces the TNF killing activity the highest, compares with gene recombinaton TNF-α sample, is equivalent to the 2000U/ml dosage range.The macrophage supernatant that stimulated 3 hours through the S311 vaccine can be measured the killing activity of TNF, and the activity that produced in 12 hours is the highest, and increasing activity later in time no longer increases, and descends gradually on the contrary, sees Fig. 1.
1.3 induce the result of mouse interferon
The S311 vaccine has the ability that stronger inducing mouse splenocyte produces interferon.In vivo test, with 4 days mouse boosting cell In vitro culture of S311 vaccine immunization, interferon activity occurs, and immunity reached peak (7.47log in 7 days
2U ± 0.31log
2U/ml), descend gradually later on.In vitro tests, normal mouse splenocyte In vitro culture adds 0.1 hundred million vaccines/ml, can measure interferon activity in 12 hours, 48 hours (8.23log that peak
2U/ml ± 0.30log
2U/ml).
1.4 research to the hemopoietic system influence
Mice rises white test: by Chinese biological goods rules version temporary provisions in 2000, the 20th page of filter preparation of staphylococcus aureus manufacturing and vertification regulation appendix 3 " leukocyte increasing test " carry out.The result: cyclophosphamide-a control group and normal control group be leukopenia relatively, statistics has significant differences, and S311 vaccine administration group and cyclophosphamide-a control group compare, and administration group leukocyte rises, statistics has significant differences, continuous 2 batches of white mice result of the test unanimities.
2 serratia marcescens Seedlings have antitumor action
2.1 inhibition test
2.1. tumor cell in vitro propagation inhibition test: to human body intestinal cancer M7609, mouse leukemia P388, human body adenocarcinoma of lung LAX, myelogenous leukemia K562, human body ovarian cancer ao10/17, IC dosage (half lethal dose) is respectively 3.94 hundred million (126 μ g/ml), 3.3 hundred million (105.55 μ g/ml), 5.5 hundred million (176.63 μ g/ml), 5.2 hundred million (168.68 μ g/ml), reaches 7.8 hundred million (250.4 μ g/ml).Conclusion: the serratia marcescens Seedling has the direct cytotoxicity of medium curative effect to tumor cell.
2.2.1 inhibition test in the body: administration is 5 times next day that the serratia marcescens Seedling being pressed 62.5 hundred million/kg, 12,500,000,000/kg, three dosage of 187.5 hundred million/kg, and three repeated trials results of three kinds of tumor spectrums are as follows:
2.1.2 the inhibition to ehrlich carcinoma: increase in life span is respectively 46.28% ± 2.83%; 54.17% ± 5.66%; 57.71% ± 6.02%.Calculate by dead suppression ratio, the suppression ratio of intraperitoneal administration is 90%.The intravenously administrable tumor killing effect is not remarkable.
2.1.3 the inhibition to P388 leukemia ehrlich ascites carcinoma: the intraperitoneal administration increase in life span is 48.72% ± 8%; 60.00% ± 11.4 4%; 61.3 6% ± 4.74%.The intravenously administrable effect is not remarkable.
2.1.4 to B
16The inhibition that the melanoma lung shifts; The intraperitoneal administration increase in life span is respectively 46.08% ± 5.27%; 51.68% ± 6.00%; 57.73% ± 3.18%.The intravenously administrable increase in life span is respectively 50.39% ± 6.51%; 58.25% ± 8.01%; 65.03% ± 7.48%.
2.1.5 intraperitoneal administration is respectively 42.6%, 49%, 56.8% to rat liver cancer HCA spleen inoculation hepatic metastases increase in life span.
2.1.6 mice is got spleen inoculation HCA hepatoma carcinoma cell, adopts quantitative reverse-transcription polymerase chain reaction technology (reverse transcriptase-polymerase chain reaction RT-PCR) detection serratia marcescens Seedling administration group and normal saline matched group nm23 gene, Tiam-1 expression of gene level.The result: the serratia marcescens Seedling can obviously suppress the expression of rat liver cancer HCA tumor metastasis related gene nm23-1 and Tiam-1.S311 vaccine administration group and normal saline control group mice compare, and the suppression ratio of primary tumors and metastasis nm23-1 cancerometastasis related gene expression is respectively 45.2%, 46.1%.The suppression ratio of Tiam-1 gene expression is respectively 29.1%, 28.7%.Show that the serratia marcescens Seedling is relevant with the expression inhibiting of nm23-1, Tiam-1 oncogene to the inhibitory action of mice HCA hepatic metastases.
3, clinical research
3.1 face observation by the husky Lei Shi treatment of cement cancerous hydrothorax 250 examples that attached tumour hospital of Shanghai Medical Univ, Jiangsu Prov. Tumour Hospital, Zhejiang Prov. Tumor Hospital, chamber, Tianjin tumour hospital, Beijing tumour hospital, Tumour Hospital Attached to Zhongshan Medical College, Beijing breast tumor hospital carry out, effective percentage 92.1% is higher than existing at present medicine for the treatment of cancerous hydrothorax.
3.2 Nanjing drum tower doctor department of cerebral surgery adopts the human experimentation of the treatment glioblastoma of injection serratia marcescens Seedling in the Omaya chemotherapy cystoma to prove, adopt the husky Lei Shi Seedling of cement Seedling curative effect highly significant, follow up a case by regular visits to the 18 routine patients in 1～4 year of postoperative, 13 example survivals, wherein 3 example survivals are 3.5 years, 4 example survivals 4.5 years, wherein 9 very high routine II～III level and IV level patients of grade malignancy, follow up a case by regular visits to 8 example survivals, and none example survival (accompanying drawing) in the ad eundem concurrent control group tumor patient 1 year.Pernicious neurogliocyte is a kind of serious disease of common prognosis mala, and prevention effect is difficult to satisfactory, the mortality rate height.The topical application of serratia marcescens Seedling provides a kind of effective ways of new raising operation survival rate for the treatment of pernicious neurogliocytoma.
3.3 Nanjing drum tower hospital chemotherapy Invasive Technology Department is treated cancer ascites 10 examples, effective percentage (CR+PR) 8 examples with the serratia marcescens Seedling.The 9 routine patient KPS scorings of treatment back raise, and quality of life improves.5 routine patient's intraperitoneal chemotherapy losers wherein, 1 routine CR behind the anticancer bacterination of S311,1 routine PR.With serratia marcescens Seedling intratumor injection treatment solid tumor 9 examples, tumor 1 example that disappears fully, tumor is dwindled 4 examples more than 50%, and tumor dwindles 50% with interior 2 examples.
3.4 the attached Yueyang of Shanghai TCM Universities hospital oncology is with serratia marcescens Seedling treatment patients with advanced cancer 16 examples, effective percentage 7 examples, wherein 5 pieces of 2 pieces of disappearances of routine patient's pulmonary carcinoma hepatic metastases kitchen range.
3.5 401 hospitals of naval are with serratia marcescens Seedling treatment psoriasis 42 examples, total effective rate 90.5%, and IgG, IgA before and after the treatment, there were significant differences for IgM.The result shows that serratia marcescens Seedling treatment psoriasis strengthens relevant with immunologic function.
3.6 Jingmen, Hubei second the People's Hospital's blood is exempted from section, with serratia marcescens Seedling treatment lupus erythematosus 56 examples, proves that the serratia marcescens Seedling has the effect of disappear lupus erythematosus skin erythema and treatment lupus erythematosus hyperpyrexia.And on treatment dry syndrome and behcet's syndrome, obtain curative effect.
3.7 condyloma acuminatum 10 examples are treated with the serratia marcescens Seedling by Haining City sexually transmitted disease (STD) inspection center, recovery from illness has 8 examples, effective 2 examples, total effective rate 100%.The used serratia marcescens Seedling of Nanjing Chinese Academy of Sciences dermatitis research is done immune inducing agent at present, is inquiring into the mechanism of serratia marcescens Seedling treatment condyloma acuminatum.
The present invention has novelty, is characterized in:
The research achievement obtains national biological product one kind new medicine certificate, numbering: traditional Chinese medicines card words (2000) S-05 number.
Study the medicine of successfully treating cancerous ascites pleural fluid and tumor with the serratia marcescens Seedling, product has novelty.Becterin of Serratia marcescens for curing to psoriasis, lupus erythematosus skin erythema, lupus erythematosus hyperpyrexia, condyloma acuminatum, Behcet comprehensively just, dry syndrome has therapeutical effect, this result of study, not only for above-mentioned treatment of diseases provides new method, and new approaches are provided for the research of these diseases.
Serratia marcescens Seedling production technology is simple.This result of study is except part has published thesis, and most contents is not published.
Claims (3)
1. treat medicine or immune formulation with the serratia marcescens preparation, aqueous injection: main component is Becterin of Serratia marcescens and solvent or solution; Lyophilized injectable powder: main component is Becterin of Serratia marcescens and excipient, it is characterized in that containing in the medicine serratia marcescens.
2. according to claims 1, it is characterized in that route of administration comprises: injection, oral, collunarium.
3. according to claims 1, it is characterized in that purposes comprises: immunomodulator is treated, be can be used as to treatment cancerous ascites pleural fluid, tumor, leukocyte increasing, auxiliary chemicotherapy, treatment psoriasis, condyloma acuminatum, behcet's syndrome, dry syndrome, flu, lupus erythematosus skin lesion and heating.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1331535C (en) * | 2005-11-03 | 2007-08-15 | 中国人民解放军海军医学研究所 | Application of viscid serratia vaccine in preparing medicine for treating bronchial asthma |
| CN105695365A (en) * | 2016-03-28 | 2016-06-22 | 蔡剑前 | Serratia marcescens and application thereof in tumor inhibition |
| CN105726580A (en) * | 2016-03-28 | 2016-07-06 | 蔡剑前 | Application of serratia marcescens vaccine in preparing medicine for preventing and/or treating immune system functional defect diseases and diabetes |
| CN105820973A (en) * | 2016-03-28 | 2016-08-03 | 蔡剑前 | Serratia marcescens vaccine and preparation method and application thereof |
-
2002
- 2002-06-05 CN CNB021119961A patent/CN1297285C/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1331535C (en) * | 2005-11-03 | 2007-08-15 | 中国人民解放军海军医学研究所 | Application of viscid serratia vaccine in preparing medicine for treating bronchial asthma |
| CN105695365A (en) * | 2016-03-28 | 2016-06-22 | 蔡剑前 | Serratia marcescens and application thereof in tumor inhibition |
| CN105726580A (en) * | 2016-03-28 | 2016-07-06 | 蔡剑前 | Application of serratia marcescens vaccine in preparing medicine for preventing and/or treating immune system functional defect diseases and diabetes |
| CN105820973A (en) * | 2016-03-28 | 2016-08-03 | 蔡剑前 | Serratia marcescens vaccine and preparation method and application thereof |
| CN105820973B (en) * | 2016-03-28 | 2019-08-13 | 蔡剑前 | A kind of Becterin of Serratia marcescens and the preparation method and application thereof |
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Effective date of registration: 20170605 Address after: 100027, No. 2, gate 3, 4, East Hospital, No. 13 South Sanlitun, Beijing, Chaoyang District Co-patentee after: Jin Feifei Patentee after: Jin Hai Address before: 100101 Beijing, Asian Sports Village, Chaoyang District overseas Chinese apartment 7-1-1501 Patentee before: Jin Hai |
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