CN101361962B - New use of thymosin alpha1 - Google Patents

New use of thymosin alpha1 Download PDF

Info

Publication number
CN101361962B
CN101361962B CN2008100719122A CN200810071912A CN101361962B CN 101361962 B CN101361962 B CN 101361962B CN 2008100719122 A CN2008100719122 A CN 2008100719122A CN 200810071912 A CN200810071912 A CN 200810071912A CN 101361962 B CN101361962 B CN 101361962B
Authority
CN
China
Prior art keywords
thymosin
thymosin alpha
diabetes
mouse
stz
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN2008100719122A
Other languages
Chinese (zh)
Other versions
CN101361962A (en
Inventor
周克夫
王世媛
韩伟
吴汉州
刘升发
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
XIAMEN BOSAI GENETIC TRANSCRIPTION TECHNOLOGY Co Ltd
Xiamen University
Original Assignee
XIAMEN BOSAI GENETIC TRANSCRIPTION TECHNOLOGY Co Ltd
Xiamen University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by XIAMEN BOSAI GENETIC TRANSCRIPTION TECHNOLOGY Co Ltd, Xiamen University filed Critical XIAMEN BOSAI GENETIC TRANSCRIPTION TECHNOLOGY Co Ltd
Priority to CN2008100719122A priority Critical patent/CN101361962B/en
Publication of CN101361962A publication Critical patent/CN101361962A/en
Application granted granted Critical
Publication of CN101361962B publication Critical patent/CN101361962B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses a new application of thymosin Alpha 1, which relates to the thymosin Alpha 1 and provides a new application of the thymosin Alpha 1. The thymosin Alpha 1 is used for preparing diabetes medicines. By the verification of animal experiments, the thymosin Alpha 1 can not only slow down the weight increase of a mouse, lower the normal fasting blood sugar of the mouse and obviously enhance the sugar tolerance of the mouse, but also prevent STZ from inducing the occurrence of diabetes of the mouse; besides, the thymosin Alpha 1 also plays an important role in protecting the structure of islet cells and the secretion level of insulin. The thymosin Alpha 1 can be used for maintaining normal glycometabolism and protecting the structure and functions of islet cells; by adopting the method of taking the thymosin Alpha 1 orally, the effect of obviously slowing down weight increase can be realized; therefore, the thymosin Alpha 1 can be applied to preparing drugs for preventing diabetes from occurring and treating diabetes and clinical practice.

Description

A kind of new purposes of thymosin
Technical field
The present invention relates to thymosin (Thymosin α 1, T α 1), especially relate to a kind of new purposes of thymosin.
Background technology
The clinical practice of thymosin starts from 20th century the mid-1970s; Its topmost contribution is to the TD treatment of diseases; Because it is for the immunoreactivity of keeping PID, autoimmune disease and cancer patient; Stimulate the lymphocytic activity of its specificity to play main effect, therefore be widely used in diseases such as therapy system property lupus erythematosus, Behcet's syndrome, rheumatoid arthritis, severe infection, bronchial asthma, acute, chronic hepatitis and tumor.In addition, because human wearing out reflects the atrophy of thymic tissue and the depletion of function significantly, thymosin can be postponed the appearance of some Senile disease, and therefore using the thymosin defying age also has extremely wide prospect.
Along with going deep into of research, people turn to the single peptide in the thymosin with research emphasis, in the hope of finding more effective clinical treatment medicine.Document shows that prophymosin-alpha (prothymosin α, ProT α) and T α 1 are the focuses in prothymosin research.
T α 1 is a kind of Acid polypeptide with heat stability, is made up of 28 aminoacid, and the pI value is 4.2, and relative molecular weight is 3108, and does not contain methionine, cysteine and aromatic amino acid.Its aminoacid sequence (1, Goldstein AL, GaraciE.Combination Therapiess [M] .NewYork:springer 1993:39-48) is:
NH2-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-COOH。
T α 1 has the biological respinse regulatory function, and its main contents comprise: (1) T α 1 can recover the function of T cell, and promotes the generation of propagation, cytokine and the receptor thereof of mature T cells, thereby enhancing body is to the immunne response ability of tumor; (2) modify tumor cell, induce the host to produce intensive immunoreation; (3) differentiation and maturation of promotion tumor cell makes malignant proliferating cell recover normalization; (4) alleviate the side effect of chemotherapy, radiotherapy.
Thymosin is from thymus the 5th component (TF5), to extract the also Acid polypeptide of purification biologically active; As immunostimulant; Can regulate immune many links, comprise activation NK cell, T cell, monokaryon and macrophage, can also stimulate the proliferation and differentiation of myeloid element; Wherein most importantly to the adjusting of T cell differentiation.Be mainly used in infectious disease such as treatment hepatitis B, hepatitis C now; Malignant tumor such as nonsmall-cell lung cancer, melanoma, hepatocarcinoma, gastric cancer; Autoimmune disease,, systemic lupus erythematosus (sle) unable etc., and the treatment of immunodeficiency like rheumatoid arthritis, serious symptom.
Research both at home and abroad (2, Rubin LA, Kurman CC, Friez ME, et al.Soluble interleukin receptorsare released from activated human lymphoid cellin vitro.J Immun, 1985,135:3172; 3, Sun Yongliang. soluble il-II receptor and infectious disease. foreign medical science epidemiology lemology volume; 1991; Find all that 18:34) SIL-2R is a kind of important immunosuppressive substance, the similar blocking factor of its effect; Increasing of its level is many with the decline of N K cytoactive and the minimizing of cd4 cell, and possibly reflect that organism immune response descends and the order of severity of the state of an illness.Thymosin be by the synthetic general name with hormonelike active polypeptides matter different of thymic epithelial cell with excretory multiple biochemical property (4, Zhang Fuguang, Liu Dianxin. thymus and thymosin progress. foreign medical science immunology fascicle, 1996,19:187).With healthy calf thymus is the injection liquid of thymic peptide alpha 1 that raw material contains various active polypeptide such as extrasin alpha; Mainly act on the differentiation of T lymphocyte, growth and sophisticated each stage; Thereby the effect of cellular immune function is regulated in performance, can strengthen simultaneously N K cell phagocytic activity (5, Muzzioli M, Mocchegiani E; Bressani N; Et al.In vitrorestoration by thymulinofNk activity of cells from old mice.Int J Immunopharma Col, 1992,14:57).Cai Wenwei etc. (6, Cai Wenwei; Lu Ping, Zhu Jian. clinical health care for the middle and old aged, 2002; 5 (2): 90-91) and Wang Zhaohai (7, clinical lung section magazine; 2004,9 (4): 357-358) adopt thymosin to strengthen diabetes and diabetes merging lunger's cellular immune function, obtain certain curative effect.The proof thymosin has positive effect aspect human body immunity improving function and the adjusting body immunity.
The major reason and the autoimmune disease of type i diabetes are closely related; Wherein mainly be because beta Cell of islet receives the attack of autoimmune cell, cause antigen-exposed, cause that immune system further reacts; Make beta Cell of islet lose in a large number; Normal secretion of insulin is affected, and blood sugar increasing forms diabetic symptom.Streptozotocin (STZ) is used widely in type i diabetes model preparation, and rat is under the disposable ejection situation of 50mg/kg and can the modeling success, and mice then reaches the modeling purpose after the injection at same dose through 5 times continuously basically.Think that at present the mechanism of action of STZ is through making body produce excessive N O; Attack and destroy beta Cell of islet, cause that pancreatic island cell antigen exposes, activate immunity of organism mechanism; Thereby a large amount of macrophages get into the damage of islet cells aggravation islet cells; Cause insulin secretion to reduce at last, cause that blood glucose increases, and brings out diabetes.Inductive mouse thymus atrophy, the obvious enlargement of kidney, and the serum anti oxidability significantly descends.
In recent years; The cause of disease of diabetes and study of pathogenesis show the generation of oxidative stress and diabetes and develop closely related (8, Cao Wenbin etc., the antioxidation micronutrient is prevented and treated the progress of diabetes, Changchun University of Traditional Chinese Medicine's journal; 2006; 22 (2): 73-74), in order to prevent the incidence and development of diabetes, people have the natural anti-reflecting oxide of preventing and treating the diabetes effect to some and have carried out systematic research; Find that they interrupt the vicious cycle that oxidation invasion and attack cause the beta Cell of islet infringement through expressing different mechanism with the effect link, a new strategy is provided thereby treat diabetes for natural anti-oxidation.
Liu Renhai etc. (9, Liu Renhai, etc. change thymosin gene Synechococcus Antioxidation Effects, Chinese Journal of Marine Drugs, 2002.2:4-7; 10, Liu Renhai; Deng. oral commentaries on classics thymosin gene Synechococcus to the research of mouse T cell subgroup effect, Xiamen University's journal (natural science edition), 2003; 4:517-520) proved that respectively commentaries on classics thymosin gene Synechococcus has significant effect aspect antioxidation and the adjusting mouse T cell subgroup; Can significantly improve healthy mice CD3, CD4 subgroup level improves body CD4/CD8 ratio.Further specifying thymosin is a kind of effective immunostimulant.
Prothymosin former (prothymosin) has 28 identical peptides of N end with thymosin, and its total length is 108~110 aminoacid, and it has the effect of adjustment immunologic function the experiment in vivo and vitro proof, can make too drastic immunologic function downward modulation; Avoid the generation of autoimmune disease, simultaneously, research recently (11, Malicet, C.; Dagorn, J.C., Neira, j.l.and Iovanna; J.L.P8 and prothymosin alpha:unity is strenthe.Cell cycle, 2006,5 (8): 829-830) also show; ProT α and apoptosis factor P8 can form complex, play the inhibition apoptosis jointly, promote fissional function.In addition, research recently (12, Mallo, G.V., Fiedler; F., Calvo, E.L., Ortiz; E.M., Vasseur, et al.cloningand expression on the rat p8 cDNA, a new gene pancreas during the acute phase of pancreatitis; Pancreas development, and regeneration, and which promostes celluar production.J.Biol.Chem.1997; 272 (51): prove also that 32360-32369) P8 can stimulate insulin β cell propagation, therefore; Infer that ProT α not only can protect islet cells to avoid the attack of autoimmune cell, can promote the division of islet cells simultaneously, thereby increase the secretion of insulin function.As far back as the Tabata eighties in 20th century, T (13, Tabata, T.; Kinoshita, Y., Fujin; S., Hato, F.; Et al.pretection by thymosin fraction 5 from streptozotocin induce diabetes in mice.Cellular and molecular biology1989; 35 (2): 121-127) adopt the put up a resistance generation of the inductive diabetes of STZ of the peptide gland factor that is separated to from the thymus of pig, certain effect arranged, but used be the complex that contains multiple composition.
Summary of the invention
The object of the present invention is to provide a kind of new purposes of thymosin.
Thymosin of the present invention is used to prepare diabetes medicament.
Confirm that through zoopery thymosin not only can slow down the increase of mice body weight, reduce the normal mouse fasting blood sugar, obviously strengthen the carbohydrate tolerance effect of mice, and can resist the generation of STZ inducing mouse diabetes; Has important function for protection islet cells structure and secretion of insulin level in addition.Thymosin of the present invention can be used for keeping normal carbohydrate metabolism, protection islet cells 26S Proteasome Structure and Function; The method of administered through oral thymosin, the effect that can also obviously slow down weight increase, so thymosin can be in the medicine and the application clinically of generation of preparation prevent diabetes and treatment diabetes.
Adopting Zadaxin (Italy matches hundred victory products, the 1.6mg/ bottle) be experiment material, and selection kunming mice and C57BL/6 are laboratory animal, and two kinds of administrations of administered through oral and subcutaneous injection can be verified the above-mentioned physiological function of thymosin.
The experimental technique of a kind of new purposes of thymosin of the present invention may further comprise the steps:
1) two approach of administered through oral and subcutaneous injection are pressed 10 a μ g/ dosed administration with thymosin;
2) whenever claimed the mice body weight at a distance from 5 days;
3) survey mice fasting glucose and carry out the carbohydrate tolerance experiment after 14 days;
4) the mice part of oral administration is catched and killed, and strips mice body fat (perirenal fat and genitals fat), weighs.Calculate total fat weight (equaling perirenal fat weight and genitals fat weight sum) and fat/body ratio and [equal (total fat weight/body weight * 100);
5) mice another part of oral administration, disposable celiac injection STZ presses 100mg/kg dosage, after the injection, surveys blood glucose once in per 10 days certainly;
6) subcutaneous injection thymosin in advance, after 14 days, mice once a day, is pressed 50mg/kg dosage through lumbar injection STZ, continuous 4 days, inject STZ certainly after, surveyed blood glucose in per 5~10 days.Get blood system after 30 days from serum, adopt the insulin detection kit to detect serum insulin levels;
7) the hypodermic while of thymosin, mice once a day, is pressed 50mg/kg dosage through lumbar injection STZ, continuous 4 days, inject STZ certainly after, surveyed blood glucose in per 5~10 days.
Through testing in the animal body, prove that thymosin has the generation of the inductive diabetes of good opposing STZ, the influence that shows good opposing diabetes-induced factor, and possessing the function that strengthens the carbohydrate tolerance effect.In addition, through oral discovery, thymosin can; Obviously slow down the effect of weight increase speed; Find that through dissecting inspection perirenal fat weight and genitals fat weight are obviously low than matched group in its body, prove that this albumen is fat in minimizing; Have important protective effect in the generation of opposing diabetes, lay the foundation for developing diabetes genetic engineering potential drug from now on.
Description of drawings
Fig. 1 is the influence of oral thymosin to the mice body weight.In Fig. 1, abscissa is a natural law (d) after the oral medicine, and vertical coordinate is mice body weight (g);-◆-be matched group ,-■-be the thymosin group.
Fig. 2 induces the diabetic mice effect for oral thymosin (10d) opposing STZ.In Fig. 2, abscissa is a natural law (d) behind the injection STZ, and vertical coordinate is blood glucose value (mmol/L);-◆-be matched group ,-■-be the thymosin group; Compare with matched group, P 0.05, significant difference; Compare with matched group, < 0.01, difference is extremely remarkable for P.
Fig. 3 is that the subcutaneous injection thymosin is to strengthening the effect of mice carbohydrate tolerance effect.In Fig. 3, abscissa is respectively 1: matched group, 2: thymosin group, vertical coordinate are TG-AUC.
Fig. 4 is subcutaneous thymosin (injecting in advance 14 days) is induced diabetes to mice opposing STZ effect.In Fig. 4, abscissa is injection streptozotocin (STZ) back natural law (d), and vertical coordinate is blood glucose value (mmol/L);-◆-be the citric acid group ,-■-be the thymosin group.
Fig. 5 is the influence of thymosin to serum insulin levels.In Fig. 5, abscissa is T α 1, and control, vertical coordinate are Pg/mL; Compare with matched group, < 0.01 difference is extremely remarkable for P.
Fig. 6 induces the effect (thymosin and STZ inject simultaneously) of diabetes to mice opposing STZ for subcutaneous thymosin.In Fig. 6, abscissa is natural law (d), and vertical coordinate is blood glucose value (mmol/L);-◆-be the citric acid group ,-■-be the thymosin group.
The specific embodiment
Following examples will combine accompanying drawing that the present invention is further described.
The materials and methods explanation that embodiment adopted as follows.
1. experiment is drawn materials and main biological reagent
Experimental animal is the C57BL/6 mice, and (20 ± 2) g is male age in 6-7 week, the SPF level, and 60 of mices are provided by Shanghai Slac Experimental Animal Co., Ltd., the quality certification number: SCXK (Shanghai) 200320003.Single cage is fed, 18~25 ℃ of room temperatures, and relative temperature 50%~80%, illumination every day 12h freely ingests, drinks water.
Streptozotocin (streptozotocin STZ, SIGMA.USA), lot number 053K1569; Citric acid (Chengdu letter He Huagongshijichang), lot number: 20040821.Insulin test kit (west, Shanghai Tang bio tech ltd).Blood-sugar detecting instrument is the Llifscan of Johson & Johnson product and supporting detection reagent paper.
2. 40 mices are equally divided into 2 groups, 20 every group, 1 group of oral route feed thymosin, one group with the equal volume normal saline as matched group.Continuous 10 days, during weighed once in per 5 days, oral thymosin is seen table 1 and Fig. 1 to the result that influences of mice body weight.
Table 1
*: compare P with matched group<0.05, significant difference; *: compare P with matched group<0.01 the extremely remarkable 5d of difference, 10d survey fasting glucose.Continuous oral thymosin 5d, mice fasting blood sugar result sees table 2 behind the 10d.
Table 2
Figure G2008100719122D00052
*: compare P with matched group<0.05
After the experiment in the 20th day, each group is got 10 respectively, strips mice body fat (perirenal fat and genitals fat), weighs.Calculate total fat weight (equaling perirenal fat weight and genitals fat weight sum) and fat/body ratio and [equal (total fat weight/body weight * 100).Oral thymosin is seen table 3 to the result that influences of mice fat weight.
Table 3
Figure G2008100719122D00053
*: compare P with matched group<0.01 difference is extremely remarkable
Residue experimental mice disposable celiac injection STZ presses 100mg/kg dosage, after the injection, surveys blood glucose once in per 10 days certainly.Matched group gives the citrate buffer solution of equal volume.Detect the same experimental group of step.Oral thymosin (10d) opposing STZ induces the diabetic mice effectiveness results to see table 4 and Fig. 2.
Table 4
Figure G2008100719122D00061
*: compare P with matched group<0.05, significant difference; *: compare P with matched group<0.01 difference is extremely remarkable
3. 20 mices are equally divided into 2 groups, 10 every group, 1 group of subcutaneous route is given thymosin, one group with the equal volume citrate buffer solution as matched group.Continuous 14 days, during weighed once in per 5 days, carried out the carbohydrate tolerance experiment on the 14th day, then lumbar injection STZ continuously once a day, press 50mg/kg dosage, continuous 4 days, inject STZ certainly after, every 5-10 days survey body weight and blood glucose are surveyed 5 times.Subcutaneous injection thymosin (continuous 14 days) is seen table 5 and Fig. 3 to the result who strengthens the effect of mice carbohydrate tolerance, and subcutaneous thymosin (injecting in advance 14 days) induces the effect of diabetes to see table 6 and Fig. 4 to mice opposing STZ.
Table 5
Figure G2008100719122D00062
*: compare P with matched group<0.05, significant difference
Table 6
Figure G2008100719122D00063
*: compare P with matched group<0.05, significant difference; *: compare P with matched group<0.01 difference is extremely remarkable
Posterior orbit was got blood in 30 days, and separation of serum is put-20 ℃ of refrigerators, adopted the ELISA method to detect wherein insulin level, and thymosin is seen Fig. 5 to the result that influences of serum insulin levels.
4. 20 mices are equally divided into 2 groups, 10 every group, 1 group of subcutaneous route is given thymosin, one group with the equal volume citrate buffer solution as matched group.Lumbar injection STZ in the time of administration once a day, presses 50mg/kg dosage, continuous 4 days, inject STZ certainly after, surveyed body weight and blood glucose, and surveyed 5 times in per 5 days.The subcutaneous injection thymosin induces effect (T α 1 and STZ the inject simultaneously) result of diabetes to see table 7 and Fig. 6 to mice opposing STZ.
Table 7
*: compare P with matched group<0.05, significant difference; *: compare P with matched group<0.01 difference is extremely remarkable
The carbohydrate tolerance experiment is calculated by following formula:
AUC=0.25×(BS?value?at?O?hour+4×BS?value?at?0.5?hours+3×BS?value?at?2?hours)。
All data of this experiment are carried out analyzing and processing through SPSS (version13.0, SPSS Inc.) software.
Thymosin is that ProT α N holds preceding 28 peptides, and research shows that it possesses same biological activity.Thymic peptide-5 also shows as the effective ingredient of thymosin and the function of similar blood sugar regulation of other thymic factor and protection islets of langerhans, and therefore, the present invention proves the theoretical foundation that thymosin has science in the prevention and the function aspect the treatment of diabetes.

Claims (1)

1. the application of thymosin in preparation type i diabetes medicine.
CN2008100719122A 2008-10-07 2008-10-07 New use of thymosin alpha1 Expired - Fee Related CN101361962B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2008100719122A CN101361962B (en) 2008-10-07 2008-10-07 New use of thymosin alpha1

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2008100719122A CN101361962B (en) 2008-10-07 2008-10-07 New use of thymosin alpha1

Publications (2)

Publication Number Publication Date
CN101361962A CN101361962A (en) 2009-02-11
CN101361962B true CN101361962B (en) 2012-05-23

Family

ID=40388690

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2008100719122A Expired - Fee Related CN101361962B (en) 2008-10-07 2008-10-07 New use of thymosin alpha1

Country Status (1)

Country Link
CN (1) CN101361962B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2476789A (en) * 2009-11-10 2011-07-13 Gl Holdings Inc Bv Use of thymosin for treatment of type 2 diabetes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4444757A (en) * 1981-11-16 1984-04-24 Research Corporation Use of thymosin as an anti-diabetes and anti-hypertensive disease agent
US6197751B1 (en) * 1997-11-10 2001-03-06 The United States Of America As Represented By The Department Of Health And Human Services Thymosin α1 promotes tissue repair, angiogenesis and cell migration
CN100342909C (en) * 2005-05-11 2007-10-17 北京双鹭药业股份有限公司 Thymosin alpha-1 aqua prepn and its prepn process and application

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4444757A (en) * 1981-11-16 1984-04-24 Research Corporation Use of thymosin as an anti-diabetes and anti-hypertensive disease agent
US6197751B1 (en) * 1997-11-10 2001-03-06 The United States Of America As Represented By The Department Of Health And Human Services Thymosin α1 promotes tissue repair, angiogenesis and cell migration
CN100342909C (en) * 2005-05-11 2007-10-17 北京双鹭药业股份有限公司 Thymosin alpha-1 aqua prepn and its prepn process and application

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ALLAN L. GOLDSTEIN et al..THYMOSINS AND ANTI-THYMOSINS: PROPERTIES AND CLINICAL APPLICATIONS.《Medical Oncology》.1986,第3卷(第3-4期),211-221. *
Enrico Garaci et al..Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application.《International Journal of Immunopharmacology》.2000,第22卷(第12期),1067-1076. *
张久聪等.胸腺肽α1的作用机制和临床应用.《细胞与分子免疫学杂志》.2006,第22卷(第4期),547-549. *
高德民, 王凤山.胸腺肽α1的特征与功能综述.《中国生化药物杂志》.2007,第28卷(第2期),136-139. *

Also Published As

Publication number Publication date
CN101361962A (en) 2009-02-11

Similar Documents

Publication Publication Date Title
CN102010473A (en) Recombinant oxyntomodulin (OXM) fusion protein, and preparation and application thereof
CN102633873B (en) Peptide, applications and preparation method thereof
CN110960539A (en) Application of mulberroside A and derivatives thereof in preparation of medicine for protecting intestinal barrier
JP2017520509A (en) Immunomodulatory therapy for autoimmune type 1 diabetes
KR20180027582A (en) Production method of egg yolk having high AF-16 content
CN107582566B (en) Methods and compositions for modulating autoimmune diseases with polyamine compounds
Prasathkumar et al. Evaluation of hypoglycemic therapeutics and nutritional supplementation for type 2 diabetes mellitus management: an insight on molecular approaches
Tang et al. Role of regulatory T cells in Schistosoma-mediated protection against type 1 diabetes
CN102861317B (en) Application of salmonella flagellin derivative in preparation of medicines for preventing and treating inflammatory bowel diseases
CN101361962B (en) New use of thymosin alpha1
KR20110119677A (en) Use of an apl peptide for the treatment of inflammatory bowel disease and type 1 diabetes
CN101631555B (en) Prophylactic agent for autoimmune disease
CN109999019B (en) Application of myristoleic acid methyl ester in preparation of product for preventing or treating metabolic syndrome or improving body energy metabolism
CN101380461A (en) Efficient thymosin enteric-coated tablets and thymosin for injection
CN116075526A (en) Interleukin 2 fusion proteins and their use in IBD
CN111700900A (en) Natural immune activator, TIL cell promoter and application thereof
CN101670098B (en) Application of restructured thymosin alpha source in preparation of medicine for preventing and treating fatty liver
CN100549025C (en) Resultant seven peptides and the synthetic method of a kind of thymopeptide-5 and pidotimod
CN114129711A (en) Application of dulaglutide in preparation of antitumor drugs
Smalley et al. Interferons: current status and future directions of this prototypic biological
KR101286743B1 (en) Pharmaceutical composition containing fenofibrate for prevention of sepsis
CN101693104A (en) New application of thymic peptide-5
Sharma et al. Asparagus racemosus aqueous root extract induced effects on cellular immune reaction of Labeo rohita (Hamilton)
CN114099493B (en) Active compound for inhibiting insulin resistance and application thereof
CN112121152B (en) Application of linatide in preparation of antitumor drugs

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20120523

Termination date: 20151007

EXPY Termination of patent right or utility model