CN102526119A - Method for enhancing dendritic cell function by using nocardia rubra cell wall skeleton - Google Patents
Method for enhancing dendritic cell function by using nocardia rubra cell wall skeleton Download PDFInfo
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Abstract
The invention relates to a method for enhancing a dendritic cell function by using a nocardia rubra cell wall skeleton. The inventor finds that the nocardia rubra cell wall skeleton can effectively mobilize and activate dendritic cells, enhances an antigen presentation function of the dendritic cells so as to be beneficial for the dendritic cells to distinguish pathogenic antigens and transmit antigenic information, and is beneficial to activating T cells, thereby promoting the specific immunities of human bodies to be effectively activated. Therefore, the nocardia rubra cell wall skeleton can be used for preparing immune preparations for treating organisms with low dendritic cell function diseases. The method in the invention provides a safe and effective immunomodulator for treating the low dendritic cell function diseases by using the nocardia rubra cell wall skeleton for activating the dendritic cells.
Description
Technical field
The present invention relates to the immunization therapy field.Particularly, the present invention relates to the immunoregulatory method of Lyopgized Nocardia rubra-cell Wall Skeleton.
Background technology
The BMDC of body can effectively transferred and activate to Lyopgized Nocardia rubra-cell Wall Skeleton as a kind of immunomodulator, and BMDC is an antigen presenting cell full-time in the body immune system, is the key cells that starts the body specific immunity.
1, the effect of BMDC
BMDC is a very important immune signal transfer sell in body immune system; Undertake full-time immune signal transfer function for the startup of specific immunity system; The T cell is the directed important immunocyte of removing pathogen in specific immunity; But the activation of T cell must rely on the immune signal transfer function of BMDC, so BMDC is the key cells in the immune system, is related to the effectively success or failure of performance of body specific immune function.
In recent years; The sight of professional person's concern has turned to human immune system's research in the industry; People more pay attention to the analysis for the reason of immunologic hypofunction; And then notice and the phenomenon of the function reduction of BMDC present like BMDC: individual little, phenomenon such as dendron is few, cell distribution density is low, people recognize that it is the major reason of immunologic hypofunction that BMDC does not play a role.
Therefore fall over each other both at home and abroad to develop all kinds of dendritic cell vaccines, be widely used in the function that strengthens BMDC, its design philosophy is: through the enhancing of dendritic cell function, and then start specific immune function.
Up to the present, still do not have ideal immunomodulator to dendritic cell function clinically, the developmental research of each item dendritic cell vaccine is not also through clinical trial.
Therefore, the function that effectively activates and transfer BMDC is still a common in the industry research topic, and people expect that a new preparation that can effectively activate and transfer dendritic cell function is born.
The indication of 2, being correlated with clinically
At present; The reason of numerous disease is exactly that body's immunological function is low clinically; And immunologic function lowly all can not normally to bring into play immunization of cell relevant with immune system, and immune system to fail to bring into play immunization of cell relevant with the BMDC immunologic information transfer function of can not normally bringing into normal play again.
The generation of the most tumor of human body at present, all with the body dendritic cell function weaken relevant because the reduction of dendritic cell function makes that the specific immune function of body can not effectively start.
Therefore because the reduction of dendritic cell function makes the signal of pathogen effectively not pass to the T cell through BMDC, cause the T cell not to be activated and play a role.
And intravital tumor mainly relies on the lymphocytic scavenging action of T, could effectively control the development of tumor.Therefore, we can say the generation and the development of tumor clinically, normally whether relevant with the function of BMDC in the immune system of body.
So, clinically about the key of prophylaxis of tumours generation and control tumor development, the function of way transfer and activated dendritic cell can be arranged exactly, this has become a focus difficult problem clinically.
3, clinically present situation
Immunization therapy to tumor is the new method of the 4th kind of treatment tumor after operation, radiotherapy, chemotherapy.The immunization therapy of tumor is current research focus; The generation of BMDC and tumor and develop relevant; If dendritic cell function defective or low in patient's body, effectively the submission tumor antigen can't activate specific immunity T cell; Then cause immunity of organism incapability and immunologic tolerance, make tumor be able to take place and development.
The immature state of BMDC can not effectively be offered antigen, become can the effectively start specific immunity key link.At present, people mainly adopt the method for exploitation dendritic cell vaccine, in order to solve the problem of dendritic cell function reduction.
Many instances prove, are played a leading role in the antineoplastic immune process by the T cell of dendritic cell ciita.With the BMDC is that basic immunization therapy becomes one of main means of following antineoplaston in the future.
The main flow research direction of this area: be to seek to use in vivo and in vitro, the compatibility is good, safer and antitumor dendritic cell vaccine mode efficiently.Situation contrast with burning hot research and development vaccine; Also there is not certain drugs can be used for transferring and activated dendritic cell.
4, the problem of dendritic cell vaccine application and existence
With the BMDC is New Policy and the main direction that basic tumor vaccine becomes immunotherapy of tumors.Through external loaded dendritic cell, feed back immunization therapy strategy in the body; The strategy of sensitization BMDC is received a lot of curative effects in the body in dendritic cell vaccine is used, but also runs into many problems:
1., In vitro culture is easy to pollute; 2., the In vitro culture cost is high; 3., cause autoimmune disease easily; 4., drug effect is unstable; 5., wait to seek best method for preparing; 6., continue the mode of the ideal tumor antigen load of screening; 7., technical difficulty is bigger; 8., large-scale culture prepares difficult; 9. the clinical treatment diversity is big; 10., tumor vaccine feeds back and notes avoiding the T cell to exhaust;
Dendritic cell tumor vaccine has shown broad clinical application prospect, will be a kind of antitumor strategy of very promising and use value.But also should see simultaneously; The BMDC anti-tumor vaccine of current research is far from reaching the effect of people's expectation; Still be in clinical experimental stage; Mainly being that many important molecular immunes mechanism as treatment immunologic escape, immunologic tolerance, cytotoxic T cell (CTL) are active reduces or reactionless, and the influence of suffered surrounding during BMDC submission antigen, remains further investigation and illustrating etc. problem.
In addition, method how to seek best BMDC preparation selects the problems such as method of the load of best maturing dendritic cell and activated state and tumor antigen also not have the answer of generally acknowledging at present.
In a word, dendritic cell vaccine does not reach people's desirable requirement as yet, still is in clinical experimental stage, and the research and development of dendritic cell vaccine also belong to crudity.
Summary of the invention
Through repeatedly bioequivalence experiment; The inventor finds can effectively transfer and the activation BMDC as the Lyopgized Nocardia rubra-cell Wall Skeleton of biological preparation; BMDC is a presenting cell full-time in the body immune system, and can BMDC activation extremely important for starting the body specific immunity.Therefore this experimental result can be explained: Lyopgized Nocardia rubra-cell Wall Skeleton is through activating and transfer BMDC; And then help that BMDC is found and identification pathogenic antigens and handling; Therefore be more conducive to activating T cell, the specific immunity of human body is easier to by effective activation.
Experimental result explanation of the present invention, Lyopgized Nocardia rubra-cell Wall Skeleton can obviously increase the density of BMDC and improve form and the function of BMDC rapidly, makes BMDC be in state of activation.
Behind the Lyopgized Nocardia rubra-cell Wall Skeleton effect on human body; Can effectively activate and strengthen the function of BMDC; And then be beneficial to and transfer the human body specific immune function; Make the T cell be easy to be activated, impel the immune activation of human body cell, cause human body specific immunity anti-tumor immune response.
Lyopgized Nocardia rubra-cell Wall Skeleton starts patient's autospecific tumor-killing mechanism through correcting the body immunodeficiency, relies on the immunologic function that activates self to remove tumor cell.
The discovery of this activation BMDC effect of Lyopgized Nocardia rubra-cell Wall Skeleton; Filled up the blank that does not have safe and effective medicine clinically for the low symptom of dendritic cell function; The doctors that are through with face the difficult situation that the low patient of numerous dendritic cell functions does not still have good plan, and the disease that makes people be directed against immunocompromised has had new treatment means.
Therefore; One aspect of the present invention relates to Lyopgized Nocardia rubra-cell Wall Skeleton and is used for regulating the purposes of the immune formulation of mammalian dendritic shape cell function in preparation, and wherein said adjusting comprises that Lyopgized Nocardia rubra-cell Wall Skeleton activates, transfers and strengthen the function of mammalian organism BMDC.
Mammal of the present invention comprises the people.
Numerous disease known in the art is lowly relevant with dendritic cell function, for example, and through the low disease of dendritic cell function of Lyopgized Nocardia rubra-cell Wall Skeleton treatment of the present invention.
In the purposes that the present invention relates to, BMDC can be a Langerhans cell.
In the purposes that the present invention relates to, the effective dose of the immune formulation that uses can confirm that as required for example the dosage of required immune formulation can be 5ug-1200ug by those skilled in the art.
In the purposes that the present invention relates to, immune formulation can pass through interior, the subcutaneous or route of exposure administration of body, is preferably with skin and contacts administration with/mucosa.
In the purposes that the present invention relates to, immune formulation can comprise pharmaceutically acceptable carrier or excipient.Any appropriate carriers or excipient that those skilled in the art knew all can be used for the present invention.Preferably, spendable excipient comprises freeze-dried formulation, emulsifiable paste dosage form or liniment.
The invention still further relates to a kind of method of regulating mammalian dendritic shape cell function; Comprise the Lyopgized Nocardia rubra-cell Wall Skeleton that directly uses effective dose to mammal, wherein said adjusting comprises that Lyopgized Nocardia rubra-cell Wall Skeleton activates, transfers and strengthen the function of mammalian organism BMDC.
Therefore, content of the present invention relates to following aspect:
1, interior and skin and mucosa through the acting body of Lyopgized Nocardia rubra-cell Wall Skeleton make the body BMDC be activated comprehensively, and then body's immunological function are greatly strengthened;
2, the enhancing of dendritic cell function is embodied in, and the density of BMDC increases, and the form of BMDC changes over state of activation;
3,, make the startup of specific immune function of body that good basis arranged through the enhancing of dendritic cell function;
4, in Lyopgized Nocardia rubra-cell Wall Skeleton effect body process, medicine is a Gamma Magnitude, safe and reliablely has an effect rapidly;
The present invention has following characteristics:
1, behind the Lyopgized Nocardia rubra-cell Wall Skeleton micro constitutent effect body, can several hrs after effective activated dendritic cell rapidly, drug effect is swift in response after the medication;
2, under the effect of Lyopgized Nocardia rubra-cell Wall Skeleton micro constitutent, the density of the BMDC of body obviously increases, and the BMDC form is launched full, and BMDC can be by abundant activation;
3, in an amount of composition effect of the Lyopgized Nocardia rubra-cell Wall Skeleton body process, body has no side effect, and shows good safety;
4, application operating is easy clinically for Lyopgized Nocardia rubra-cell Wall Skeleton, makes things convenient for the patient to use.
Description of drawings
Fig. 1: Langerhans cell colored graph.A is 288 *, b is 1152 *.
Fig. 2: Na Kejia group administration mice and dextran control group mice Langerhans cell figure.
Fig. 3: Na Kejia group and dextran group are to the broken line graph that influences of the LC of mice ear cell.
The specific embodiment
Test material
1. medicine: Lyopgized Nocardia rubra-cell Wall Skeleton (Na Kejia), source: Liaoning Nakejia Biological Pharmaceutical Co., Ltd., authentication code: the accurate word S20030009 of traditional Chinese medicines.
2. animal: 6～8 all Healthy female BALB/c mouses, SPF level, 14, body weight (20 ± 2) g.The source: Beijing cloud Pedicellus et Pericarpium Trapae animal breeds factory.
3. mouse-anti people HLA-DR, 250 μ l number ZM-0136, and Bioisystech Co., Ltd of China fir Golden Bridge produces in Beijing.
4. Mus ABC test kit: 1/4kit, Bioisystech Co., Ltd of China fir Golden Bridge in Beijing (U.S. VECTOR company).
5. the anti-people HLA-DR of rabbit (Rabbit Anti-HLA-DR), 0.2ml, numbering BS-1198R, Beijing Bo Aosen Bioisystech Co., Ltd.
6. rabbit immunohistochemical staining test kit: 3ml numbers SP-0023, Beijing Bo Aosen Bioisystech Co., Ltd.
7. rat anti people HLA-DR, 0.25ml, numbering MCA71R, serotec company produces.
8. the Mus IgG of the biotinylation rabbit Chinese People's Anti-Japanese Military and Political College (H+L) numbers ZB-2040, and Bioisystech Co., Ltd of China fir Golden Bridge produces in Beijing.
9.AEC zymolyte test kit: 2ml, numbering zli-9036, lot number K106718A, effect duration 08/2011, Bioisystech Co., Ltd of China fir Golden Bridge in Beijing.
10.PBS buffer: 2000ml/ bag, Bioisystech Co., Ltd of China fir Golden Bridge in Beijing.
11.GVA mountant: 5ml, numbering zli-9051, lot number P92304H, effect duration 07/2011, Bioisystech Co., Ltd of China fir Golden Bridge in Beijing.
EXPERIMENTAL DESIGN
Checking thinking of the present invention is to utilize the principle of bioequivalence; Adopt zooperal mode; The inventor has selected the breadboard experimental technique of Chinese Medical Sciences University's state key subject; Through repeatedly testing in many group mice bodies, detect and the calculating of the statistical calculation method of science through advanced detection means, prove that Lyopgized Nocardia rubra-cell Wall Skeleton can transfer the usefulness with activated dendritic cell.
Animal experiment scheme and step
The thinking of experimental program and design principle:
Adopt white mice to carry out the bioequivalence experiment, be divided into several experimental grouies and two matched groups immediately,,, formulate checking zoopery scheme of the present invention in conjunction with inventor self features of experiment with reference to the related experimental methods of professional paper.
Embodiment 1
Test procedure
1. divide into groups: get 3 mices and be divided into three groups and numbering at random, promptly receive can good group (No. 2) and dextran vehicle control group (No. 3) for blank control group (No. 1), 20 μ g.Adopt anti-and two anti-(rat anti people HLA-DR) for No. 1, No. 3, No. 2 one anti-for adopting the anti-people HLA-DR of rabbit.
2. operating procedure:
Get the blank control group mice No. 1, operate, corium is separated with epidermis according to the isolating method of the true epidermis of mice.No. 2 and No. 3 mices inject respectively that 0.2ml receives can good solution and 0.2ml Dextran 40 solution, cut ear in second day and separate, and carry out immunohistochemical staining, microscopy.
The true epidermis of mice separates:
1. etherization mice is cut the part of ear.
2. strike off the sebum and the scurf on surface with blade, PBS washes 3-5 time repeatedly.
3. the skin that separates the Mus ear with tweezers.Blade strikes off cartilage, and is cut into 0.5cm * 0.5cm fritter.
4. add 37 ℃ of water-baths in the EDTA separating medium (PH7.2), take out skin graft behind the 80min separately, stay epidermis subsequent use true epidermis.
3. antibody labeling:
1. fixing 4 ℃ of epidermises of acetone room temperature, 20min, PBS washes 5min, 2 times;
2. epidermis is put into the microcentrifugal tube that contains 1: 100 rat anti people HLA-DR (No. 2 be the anti-people HLA-DR of rabbit) antibody and is shaken, and 4 ℃ are spent the night;
3. take out epidermis, PBS washes 5min, 2 times, put into the microcentrifugal tube of the Mus IgG of the rabbit Chinese People's Anti-Japanese Military and Political College (No. 2 for the goat anti-rabbit igg) antibody of the bioid that contains 1: 50, hatch 1.5h after, PBS washes 5min, 2 times;
4. epidermis is put into and is added Radix Cochleariae officinalis enzyme labelling chain enzyme avidin microcentrifugal tube, hatches 60min, and PBS washes 5min, 2 times
4. immunohistochemical staining (using) according to the AEC test kit
Before the dyeing, respectively No. 123 each 50 μ l of reagent are joined the microcentrifugal tube that fills the 1ml distilled water, keep in Dark Place, effective in the 30min.
1. under the room temperature, carefully add the dyeing working solution of 100 μ l, put into epidermis (corium is towards last), it is immersed in the working solution at microscope slide.
2. hatch 10 under the room temperature to 20min, or occur red until sample.
3. remove supracutaneous dyeing working solution.
4. under the room temperature, slide inserted in the PBS buffer solution that 50ml provides for oneself soak 5s.
5. remove supracutaneous PBS buffer solution
6. air-dry back glycerin gelatine mounting.。
7. promptly be engraved under the optical microscope and observe: the positive presents redness.
Embodiment 2
Test procedure
1. divide into groups: get 8 mices and be divided into two groups and numbering at random, promptly receive can good group (1-6 number) and dextran vehicle control group (1-2 number for 40 μ g.)
2. operating procedure:
The Na Kejia solution of Na Kejia group injection 0.2ml40 μ g/ml, the Dextran 40 solution of dextran matched group injection 0.2ml3%, concrete administration and get the ear dyeing time and see the following form:
The true epidermis of mice separates:
1. etherization mice is cut the part of ear.
2. strike off the sebum and the scurf on surface with blade, PBS washes 3-5 time repeatedly.
3. the skin that separates the Mus ear with tweezers.Blade strikes off cartilage, and is cut into 0.5cm * 0.5cm fritter.
4. add 37 ℃ of water-baths in the EDTA separating medium (PH7.2), take out skin graft behind the 80min separately, stay epidermis subsequent use true epidermis.
3. antibody labeling:
1. fixing 4 ℃ of epidermises of acetone room temperature, 20min.PBS washes 5min, 2 times;
2. epidermis is put into the microcentrifugal tube that contains 1: 100 rat anti people HLA-DR antibody, and 4 ℃ are spent the night;
3. take out epidermis, PBS washes 5min, 2 times, put into the microcentrifugal tube of the Mus IgG of the rabbit Chinese People's Anti-Japanese Military and Political College antibody of the bioid that contains 1: 50, hatch 1.5h after, PBS washes 5min, 2 times;
4. epidermis is put into and is added Radix Cochleariae officinalis enzyme labelling chain enzyme avidin microcentrifugal tube, hatches 60min, and PBS washes 5min, 2 times.
4. immunohistochemical staining (using) according to the AEC test kit
Before the dyeing, respectively 1,2, No. 3 each 50 μ l of reagent is joined the microcentrifugal tube that fills the 1ml distilled water, keep in Dark Place, effective in the 30min.
1. under the room temperature, add the dyeing working solution of 100 μ l, put into epidermis (corium is towards last), it is immersed in working solution at microscope slide.
2. hatch 10 under the room temperature to 20min, or occur red until sample.
3. remove supracutaneous dyeing working solution.
4. under the room temperature, slide inserted in the PBS buffer solution that 50ml provides for oneself soak 5s.
5. remove supracutaneous PBS buffer solution
6. air-dry back glycerin gelatine mounting.。
7. promptly be engraved under the optical microscope and observe: the positive presents redness.
Observation index and criterion
1. observation index: 10 continuous visuals field of each BIAO and BEN picked at random are counted, and LC is to see cell space and dendron is confirmed simultaneously.Positive LC density is (individual/mm
2)=positive cell number/epidermis area.
2. staining power is judged: dye-free negative (-); Slight stain is the weak positive (±); More shallow positive (+) dyes; Dyeing is moderate positive (++) more deeply; Dyeing deeply is strong positive (+++).
3. statistical method: LC density relatively adopts paired t check
Result of the test
The antibody that embodiment 1 uses Serotec company to produce dyes, and No. 1 sheet is seen many cellularity of dying salmon pink under the mirror, through being judged to be Langerhans cell (Fig. 1, a figure be 288 *, b figure is 1152 *), explains and dyes successfully.
2 couples of Na Kejia of embodiment tentatively study the effect of mice ear Langerhans cell.
Through overtesting, each organizes mice Langerhans cell uniform dyeing, and each picture group sheet is seen Fig. 2 (picture be 288 *).Fig. 3 has shown Na Kejia group and the dextran group broken line graph that influences to the LC of mice ear cell.
The density of table 1, mice ear Langerhans cell (t check) sees the following form:
Sum up
In embodiment 1: observed orange-red structure under the mirror, confirm as Langerhans cell.
In embodiment 2: through knowing to the analysis of test structure:
1 can see from the contrast of picture, and Na Kejia group administration mice (2,3,4,5, No. 6 mices) ear's Langerhans cell all obviously is better than not administration mice (No. 1 mice) and is higher than the dextran matched group on quantity and cellular morphology.
2 can see from density t check table, and Na Kejia group administration mice (2,3,4,5, No. 6 mices) ear's Langerhans cell density all apparently higher than administration mice (No. 1 mice) not, also is higher than the dextran matched group simultaneously.
3 can see from the broken line graph of density, and in general, Na Kejia group administration mice LC cell density does not have significant change with the increase of administration number of times.
Through above Several Analysis, but explain that receiving Canon enough promotes the increase of the quantity of mice ear Langerhans cell, Langerhans cell becomes big, full, dendron quantity simultaneously increases, and explains that Na Kejia has activation to the function of Langerhans cell.
1, statistical data explanation: Lyopgized Nocardia rubra-cell Wall Skeleton significantly increases the density of BMDC;
2, contrast caption: Lyopgized Nocardia rubra-cell Wall Skeleton obviously improves the form of BMDC;
3, comprehensive conclusion: the effective activation of Lyopgized Nocardia rubra-cell Wall Skeleton and transferred BMDC.
Claims (10)
1. Lyopgized Nocardia rubra-cell Wall Skeleton is used for regulating the purposes of the immune formulation of mammalian dendritic shape cell function in preparation.
2. purposes according to claim 1, wherein said adjusting comprise that Lyopgized Nocardia rubra-cell Wall Skeleton activates, transfers and strengthen the function of mammalian organism BMDC.
3. purposes according to claim 1 and 2 is characterized in that described BMDC comprises Langerhans cell.
4. according to each described purposes among the claim 1-3, the dosage that it is characterized in that described immune formulation is 5ug-1200ug.
5. according to each described purposes among the claim 1-4, it is characterized in that described immune formulation is through interior, the subcutaneous or route of exposure administration of body.
6. according to each described purposes among the claim 1-4, it is characterized in that described immune formulation comprises pharmaceutically acceptable carrier or excipient.
7. according to the purposes of claim 6, it is characterized in that described excipient comprises freeze-dried formulation, emulsifiable paste dosage form or liniment.
8. regulate the method for mammalian dendritic shape cell function, comprise the Lyopgized Nocardia rubra-cell Wall Skeleton that directly uses effective dose to mammal.
9. method according to claim 8, wherein said adjusting comprise that Lyopgized Nocardia rubra-cell Wall Skeleton activates, transfers and strengthen the function of mammalian organism BMDC.
10. according to Claim 8 or 9 described methods, it is characterized in that described BMDC comprises Langerhans cell.
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| CN2010106086915A CN102526119A (en) | 2010-12-23 | 2010-12-23 | Method for enhancing dendritic cell function by using nocardia rubra cell wall skeleton |
| CN2011800618259A CN103269705A (en) | 2010-12-23 | 2011-12-23 | Method for enhancing dendritic cell function by nocardia rubra cell wall skeleton |
| PCT/CN2011/084582 WO2012083884A1 (en) | 2010-12-23 | 2011-12-23 | Method for enhancing dendritic cell function by nocardia rubra cell wall skeleton |
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| CN108795860A (en) * | 2017-05-03 | 2018-11-13 | 辽宁格瑞仕特生物制药有限公司 | Lyopgized Nocardia rubra-cell Wall Skeleton is as CD8+The purposes of T cell enhancer of proliferation |
| CN108795859A (en) * | 2017-05-03 | 2018-11-13 | 辽宁格瑞仕特生物制药有限公司 | Purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as natural killer cells enhancer of proliferation |
| CN114402064A (en) * | 2020-01-21 | 2022-04-26 | 辽宁格瑞仕特生物制药有限公司 | Use of nocardia rubra cell wall skeleton in regenerative medicine |
| CN115025128A (en) * | 2022-06-24 | 2022-09-09 | 辽宁格瑞仕特生物制药有限公司 | Application of nocardia rubra cell wall skeleton in treatment of cervical lesion |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111683670A (en) * | 2019-01-09 | 2020-09-18 | 辽宁格瑞仕特生物制药有限公司 | Use of nocardia rubra cell wall skeleton in treatment of recurrent aphthous ulcers |
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| CN1935262A (en) * | 2005-09-23 | 2007-03-28 | 沈阳胜宝康生物制药有限公司 | Application of nocardia rubra cell wall skeleton in preparation of anti-human papilloma virus medicine |
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| JP4859341B2 (en) * | 2001-07-19 | 2012-01-25 | 昭 林 | Human immunotherapy |
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| CN1935262A (en) * | 2005-09-23 | 2007-03-28 | 沈阳胜宝康生物制药有限公司 | Application of nocardia rubra cell wall skeleton in preparation of anti-human papilloma virus medicine |
| CN101073583A (en) * | 2006-05-19 | 2007-11-21 | 沈阳胜宝康生物制药有限公司 | Application of nocardia rubra cell wall skeleton in preparation of medicines |
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Cited By (4)
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| CN108795860A (en) * | 2017-05-03 | 2018-11-13 | 辽宁格瑞仕特生物制药有限公司 | Lyopgized Nocardia rubra-cell Wall Skeleton is as CD8+The purposes of T cell enhancer of proliferation |
| CN108795859A (en) * | 2017-05-03 | 2018-11-13 | 辽宁格瑞仕特生物制药有限公司 | Purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as natural killer cells enhancer of proliferation |
| CN114402064A (en) * | 2020-01-21 | 2022-04-26 | 辽宁格瑞仕特生物制药有限公司 | Use of nocardia rubra cell wall skeleton in regenerative medicine |
| CN115025128A (en) * | 2022-06-24 | 2022-09-09 | 辽宁格瑞仕特生物制药有限公司 | Application of nocardia rubra cell wall skeleton in treatment of cervical lesion |
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| CN103269705A (en) | 2013-08-28 |
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