CN108992660A - Application of the people sDR5-Fc recombination fusion protein as pancreatitis treatment drug - Google Patents
Application of the people sDR5-Fc recombination fusion protein as pancreatitis treatment drug Download PDFInfo
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Abstract
A kind of application the present invention provides people sDR5-Fc recombination fusion protein as pancreatitis treatment drug, specifically disclose a kind of application of people sDR5-Fc recombination fusion protein in the drug that preparation treats or prevents pancreatitis, the people sDR5-Fc recombination fusion protein sequence is as shown in SEQ ID No.1, SEQ ID No.2, SEQ ID No.3 or SEQ ID No.4, or has and SEQ ID No.1, SEQ ID No.2,95% or more homology of SEQ ID No.3 or SEQ ID No.4 and recombination fusion protein with the same function.
Description
Technical field
The present invention relates to a kind of fusion proteins, and in particular to a kind of people sDR5-Fc recombination fusion protein and its as preparation
Treat the application in the drug of pancreatitis.
Background technique
Pancreatitis is a kind of diseases associated with inflammation of pancreas, and symptom there are many pathogenic factor and clinically is in diversity.
It secretes in pancreatic acinar cell, the pancreas protoenzyme (especially trypsase) with digestion food function under certain pathologic conditions
Can be in pancreas by abnormal activation, and these protoenzymes are activated in small intestine under normal circumstances.Be activated in pancreas this
A little protoenzymes can cause pancreas autodigestion, to induce acute pancreatitis.Acute pancreatitis upsets greatly body physiological function,
It is obvious to the damage of each important organ, therefore the death rate is very high, and also there is no specific treatment measure at present, does not also have at present clinically
The drug of special effectively treatment acute pancreatitis.Acute pancreatitis is common clinical, and disease incidence is high.Due to acute pancreatitis
Morbidity is anxious, and progression of the disease is fast and complicated, and can rapidly develop from the local patholoic change of initial pancreatic tissue becomes systemic inflammatory response
Syndrome (systematic inflammatory response syndrome, SIRS), pyemia, septic shock or even
Multiple organ failure, in addition it is dead, and treatment is very intractable, although clinical treated using composite treatment, effect is not
Satisfied, overall mortality rate is still up to 5%~13.6%, therefore studies new active drug and be of great significance.
The common disease factor of pancreatitis has: disease of biliary tract, heavy drinking, overeating.The pathogenesis of pancreatitis is complicated, with
Toward research focus mostly on inflammatory factor, oxidative stress, in terms of.In recent years it is found that Apoptosis is in acute pancreas
It plays an important role during the occurrence and development of adenositis, it takes part in the tissue damage of acute pancreatitis.
The base therapy principle of pancreatitis is: 1) inhibiting to reduce pancreatic secretion.Fasting, gastrointestinal decompression.Use suppression pancreatin system
Agent.2) Hemorrhagic shock, correction water, electrolyte balance.Replenishment of blood content supplements electrolyte, calcium.3) acid suppression, anticholinergic agents are answered
With.Acid suppression: inhibit pancreatic secretion indirectly.Anticholinergic drug: relieving spasm and pain.Antalgesic Reusability has additive risk.4) resist
Raw element application: to severe pancreatitis, vein uses broad-spectrum antibiotic.
Growth hormone release inhibiting hormone: gastric acid inhibitory, pepsin, gastrin secretion influence gastrointestinal tract absorption and power, reduce internal organ blood
Flow reduces pancreas Endocrine and exocrine functions.Adverse reaction has nausea, dizziness, flushed face, dislikes when injection speed is too fast
The heart, vomiting, of short duration blood glucose decline.
Gabexate: non-peptide albuminoid enzyme inhibitor inhibits the enzyme activity such as trypsase, kininase, plasmase, fibrin ferment
Property, mitigate injury of pancreas.Adverse reaction has local vascular pain, superficial phlebitis；Fash, flushed face；Individual anaphylactic shocks.
Ulinastatin can inhibit the release and activity of relevant enzyme, effectively control pancreatitis progression of the disease, reduce pancreatitis simultaneously
Send out the generation of disease.
Non-steroid anti-inflammatory drug: it by inhibiting cyclooxygenase-2 activity, reduces prostaglandin and generates, mitigate inflammatory reaction.Stomach
Gut Injury is the most common side reaction of this kind of drug, including (such as gastroduodenal is worn for indigestion symptom and severe complication
Hole, obstruction and bleeding etc.).
It can be seen that the medicament categories for the treatment of pancreatitis are less at present, and based on symptomatic treatment, offer limited effectiveness, often not
It can avoid side effects of pharmaceutical drugs, or even generate serious adverse reaction.Due to lacking for cell pathology physiology early stage critical event
The understanding and understanding of generation, special and effective treatment means are also very poor at present, need to develop new therapeutic agent.
Death receptor 5 (Death receptor 5, DR5) is the member of Tumor Necrosis Factor Receptors family, in activation
Peripheral blood lymphocytes, inflammatory tissue, expression is high in ischemic tissue.DR5 receptor causes one after combining with ligand/TRAIL
Series of signals cascade reaction causes Apoptosis.
The transmembrane protein that people DR5 albumen is made of 411 amino acid.Wherein 1~55 amino acids are signal peptides, 84~
179 amino acids be containing 2 rich in cysteine repeat function area chain combined area, 184~206 amino acids be across
Film area, intracellular region contain death domain.Soluble DR5 (soluble DR5, sDR5) is DR5 without the solvable of trans-membrane region
Property form, due to a lack of trans-membrane region cannot express on cell membrane and it is extracellular to be secreted into.Although sDR5 holding is matched with TRAIL
The activity that body combines, but the Apoptosis of TRAIL-DR5 mediation cannot can be blocked to intracellular transduction apoptotic signal.And
SDR5 is human body oneself protein, has the advantages that small toxicity, non-immunogenicity, the great critical treatment drug as pancreatitis
Potential quality.Currently, sDR5 whether there is therapeutic effect for pancreatitis, report there is no both at home and abroad.
Summary of the invention
To solve the above-mentioned problems, a kind of method of high-efficiency low-toxicity for treating pancreatitis is provided, the present invention provides one kind
People's sDR5-Fc recombination fusion protein, sequence such as SEQ ID No.1, SEQ ID No.2, SEQ ID No.3 or SEQ ID
Shown in No.4, or have same with SEQ ID No.1, SEQ ID No.2,95% or more SEQ ID No.3 or SEQ ID No.4
Source property and recombination fusion protein with the same function.
Another aspect of the present invention provides people sDR5-Fc recombination fusion protein above-mentioned and treats or prevents pancreas in preparation
Application in scorching drug.
Another aspect of the present invention provides a kind of tumor necrosin relative death inducing ligand antagonist and controls in preparation
Application in the drug for the treatment of or prevention pancreatitis.
Wherein, the tumor necrosin relative death inducing ligand antagonist is selected from people sDR5-Fc above-mentioned recombination and melts
Hop protein.
The pancreatitis is acute pancreatitis or chronic pancreatitis in the inventive solutions.
Another aspect of the present invention provides a kind of pharmaceutical composition for treating pancreatitis, and it includes sDR5-Fc recombinations to melt
Hop protein sequence or the nucleotide sequence and its pharmaceutically acceptable auxiliary material for encoding the protein sequence.
The present invention discloses above-mentioned recombination fusion protein, can form pharmaceutical preparation together with pharmaceutically acceptable auxiliary material
Composition is to more stably play curative effect, the preparations, preferably water such as preparation can commonly be suspended for pharmaceutical field, water needle, freeze-drying
Needle or lyophilized preparation can pharmaceutically receive the water needle or lyophilized preparation of above-mentioned recombination fusion protein disclosed by the invention
Auxiliary material include one or a combination set of surfactant, solution stabilizer, isotonic regulator and buffer, wherein surfactant
Including nonionic surface active agent such as Polyoxyethylene Sorbitol Fatty Acid Esters (polysorbas20 or 80)；Triton；Dodecyl sulphur
Sour sodium (SDS)；Poloxamer (such as poloxamer 188)；Pluronics；Sodium Laurylsulfate；Myristyl, sub- oil base or ten
Eight alkylsarcosines etc., additional amount should make recombination fusion protein granulating trend minimum, and solution stabilizer can be carbohydrate, packet
Reducing sugar and nonreducing sugar are included, amino acids include monosodium glutamate or histidine, and alcohols includes propylene glycol, poly- second two
The additional amount of one or a combination set of alcohol, trihydroxylic alcohol, advanced sugar alcohol, solution stabilizer should make the preparation eventually formed in this field
Technical staff think to reach and keep stable state in stable time, isotonic regulator can be one of sodium chloride, mannitol,
Buffer can be one of TRIS, phosphate buffer, histidine buffering liquid.
For sDR5-Fc recombination fusion protein when to animal administration including people, dosage is because of patient in the present invention
Age and weight, disease traits and seriousness and administration route and it is different, the result and various feelings of zoopery can be referred to
Condition, total dosage is no more than a certain range.The dosage being specifically injected intravenously is 0.01~3000mg/ days.
People sDR5-Fc recombination fusion protein plays protection to the acute pancreatitis mice that tree toad element induces and makees in the present invention
With the mice pancreatic inflammatory reaction of reduction tree toad element induction.The substance can pass through pancreas group during reduction acute pancreatitis
Oedema, serum amylase are knitted to reduce inflammatory reaction, there is significant protective effect to pancreatitis, which can be used for preparing
Drug is used for the prevention and treatment of acute and chronic pancreatitis, reduces the incidence and degree of inflammation of Clinical Acute pancreatitis.
Beneficial effect
1, the present invention provides new research direction and treatment means for the treatment of pancreatitis.In pancreatitis, no matter cause
Disease is the reason is that, will necessarily be related to the apoptosis of cell.TRAIL-DR5 access participates in acute and chronic pancreas caused by many factors
Inflammation, therefore adaptation range is extensive.
2 and sDR5-Fc fusion protein derives from the protein component of human body itself, and highly-safe, toxic side effect is smaller.
Detailed description of the invention
Fig. 1 mice pancreatic factor levels compare (average value ± SD).It is examined using t, treatment group's mice pancreatic coefficient is significant
Property be lower than model group, p < 0.05.
Fig. 2 mice pancreatic tissue trypsase activity level compares (average value ± SD).It is examined using t, treatment group mouse
Trypsase vigor conspicuousness is lower than model group, p < 0.01.
Fig. 3 mice serum amylase activity level compares (average value ± SD).It is examined using t, treatment group's mice serum forms sediment
Powder enzyme activity conspicuousness is lower than model group, p < 0.01.
Specific embodiment
In order to help to understand the present invention, it is provided below and describes the embodiment of a series of experiments result.Certainly, it cannot incite somebody to action
Experiment explanation related to the present invention is that especially limitation is of the invention, and thinks the mesh in those skilled in the art's technical scope
This kind of change of the invention that is preceding known or further developing belongs to the scope of described herein and claimed hereinafter protection.
In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition, or according to manufacturer
Proposed condition.Used various reagents and sample, are commercial product unless otherwise indicated in embodiment.
The design and recombination of the recombination sDR5-Fc expressed sequence of embodiment 1
Inventor passes through long-term experience accumulation, and people sDR5 is carried out merging for various ways with Fc by construction of fusion protein,
Mass spectrometry results show that destination protein N-terminal is unstable, it may appear that multiple amino acid shearings design accordingly and prepare a plurality of amino
No.1~4 acid sequence SEQ ID, wherein splicing isomer ratio contained by the albumen of SEQ ID No.1 is minimum, is under 37 degree
1%, and SEQ ID No.2 is 31%；SEQ ID No.3 is 49%；SEQ ID No.4 is 52%, and equal conspicuousness is higher than SEQ
The splicing isomer ratio of ID No.1, therefore the purity of protein of SEQ ID No.1 is optimal, it is most stable.
SEQ ID No.1
SSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTTRNTVCQCEEG
TFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM
ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP
APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ ID No.2
ITQQDLAPQQRAAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTT
RNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEGSSNTKVDKKVEPKSCDKTHTCPPCPA
PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV
LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK；
SEQ ID No.3
ITQQDLAPQQRAAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEV
ELSPCTTTRNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEEPKSCDKTHTCPPCPAPEL
LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ
DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ ID No.4:
AAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTTRNT
VCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK
VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
The aminoterminal of the SEQ ID No.1-4 fusion protein is the solvable segment of human death receptor 5；C-terminus is that people is immune
The Fc segment of globulin 1 (IgG1).
The solvable segment of the human death receptor 5 have as SEQ ID NO.5, SEQ ID NO.6, SEQ ID No.7 or
Amino acid sequence shown in SEQ ID No.8, or have and SEQ ID NO.5, SEQ ID NO.6, SEQ ID No.7 or SEQ
95% or more homology of ID No.8 and albumen with the same function.
The amino acid sequence of the Fc segment of the human immunoglobulin(HIg) 1 (IgG1) is as shown in SEQ ID NO.9.
It is directly connected between the solvable segment of human death receptor 5 and the Fc segment of human immunoglobulin(HIg) 1.
SEQ ID NO.5:
SSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTTRNTVCQCEEGTFREEDSP
EMCRKCRTGCPRGMVKVGDCTPWSDIECVHKE；
SEQ ID NO.6:
ITQQDLAPQQRAAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTT
RNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEGSSNTKVDKKV；
SEQ ID NO.7:
ITQQDLAPQQRAAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTT
RNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKE；
SEQ ID No.8:
AAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTTRNTVCQCEEGT
FREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKE；
SEQ ID NO.9:
EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR
EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K。
Embodiment 2: people's sDR5-Fc antibody fusion protein treats pancreatitis.
60 kunming mices are randomly divided into normal group, model group and 9mg/kg sDR5-Fc treatment group (SEQ ID No.1
Or SEQ ID No.2 or SEQ ID No.3 or SEQ ID No.4), every group 10, female is fifty-fifty.Fasting 14 hours before modeling,
Normal water.Chmice acute pancreatitis model is caused using tree toad element joint lipopolysaccharides (lipopolysaccharide, LPS): being used
Dosage is that mouse is injected intraperitoneally in the tree toad element of 100 μ g/kg, continuous 6 times, every 1 hour 1 time, is injected in last time
The LPS of 10mg/kg is injected intraperitoneally after tree toad element immediately, completes modeling.
Normal group mouse gives 10ml/kg physiological saline；Model group mouse gives 10ml/kg physiological saline after modeling；
9mg/kg sDR5-Fc, administered volume 10ml/kg give after modeling in treatment group.18 hours after modeling, under all mouse jaws
Mouse is put to death in venous blood collection, dislocation, takes pancreatic tissue, carries out pathological study, calculates pancreas coefficient: pancreas coefficient=pancreas
Gland weight in wet base (mg)/mouse weight (g), detects pancreatic tissue trypsase (trypsin) and serum amylase (amylase) is living
Power, and carry out statistical analysis.
Normal group mouse drinking-water, activity are good, any abnormal response do not occur, pancreatic tissue is without obvious abnormal, pancreas
Glandular structure distinct, color is normal, no oedema, hyperemia.Model group mice pancreatic tissue volume increases, boundary structural fuzzy,
Obvious tumefaction and hyperemia.The slight swelling of sDR5-Fc treatment group pancreas, boundary structure is more visible, and color is close to normal group, bleeding
It is few.SDR5-Fc treatment group mice pancreatic coefficient, pancreas tissue trypsase are horizontal and serum-amylase level is substantially less than model
Group, close to normal group mouse.Show that sDR5-Fc recombination fusion protein can effectively treat pancreatitis.Specific test result is referring to attached
Fig. 1-3, by attached drawing it can be seen that treatment group's mice pancreatic coefficient conspicuousness is lower than model group, p < 0.05.Treatment group's mouse pancreas
Prolease activity conspicuousness is lower than model group, p < 0.01.Treatment group's mice serum amylase activity conspicuousness be lower than model group, p <
0.01。
Other than these contents illustrated and described herein, various improvement of the invention for those skilled in the art and
Speech can by the description of front it is clear that and they belong to Claims scope below.
SEQUENCE LISTING
<110>Shenzhen Zhongke Aishen Medicine Co., Ltd.
<120>application of the people sDR5-Fc recombination fusion protein as pancreatitis treatment drug
<160> 9
<170> PatentIn version 3.3
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Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe Cys Leu
35 40 45
Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro Cys Thr
50 55 60
Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe Arg Glu
65 70 75 80
Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys Pro Arg
85 90 95
Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu Cys
100 105 110
Val His Lys Glu Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
115 120 125
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
130 135 140
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
145 150 155 160
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
165 170 175
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
180 185 190
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
195 200 205
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
210 215 220
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
225 230 235 240
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
245 250 255
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
260 265 270
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
275 280 285
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
290 295 300
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
305 310 315 320
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
325 330 335
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
340 345
<210> 5
<211> 109
<212> PRT
<213>fusion protein
<400> 5
Ser Ser Pro Ser Glu Gly Leu Cys Pro Pro Gly His His Ile Ser Glu
1 5 10 15
Asp Gly Arg Asp Cys Ile Ser Cys Lys Tyr Gly Gln Asp Tyr Ser Thr
20 25 30
His Trp Asn Asp Leu Leu Phe Cys Leu Arg Cys Thr Arg Cys Asp Ser
35 40 45
Gly Glu Val Glu Leu Ser Pro Cys Thr Thr Thr Arg Asn Thr Val Cys
50 55 60
Gln Cys Glu Glu Gly Thr Phe Arg Glu Glu Asp Ser Pro Glu Met Cys
65 70 75 80
Arg Lys Cys Arg Thr Gly Cys Pro Arg Gly Met Val Lys Val Gly Asp
85 90 95
Cys Thr Pro Trp Ser Asp Ile Glu Cys Val His Lys Glu
100 105
<210> 6
<211> 138
<212> PRT
<213>fusion protein
<400> 6
Ile Thr Gln Gln Asp Leu Ala Pro Gln Gln Arg Ala Ala Pro Gln Gln
1 5 10 15
Lys Arg Ser Ser Pro Ser Glu Gly Leu Cys Pro Pro Gly His His Ile
20 25 30
Ser Glu Asp Gly Arg Asp Cys Ile Ser Cys Lys Tyr Gly Gln Asp Tyr
35 40 45
Ser Thr His Trp Asn Asp Leu Leu Phe Cys Leu Arg Cys Thr Arg Cys
50 55 60
Asp Ser Gly Glu Val Glu Leu Ser Pro Cys Thr Thr Thr Arg Asn Thr
65 70 75 80
Val Cys Gln Cys Glu Glu Gly Thr Phe Arg Glu Glu Asp Ser Pro Glu
85 90 95
Met Cys Arg Lys Cys Arg Thr Gly Cys Pro Arg Gly Met Val Lys Val
100 105 110
Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu Cys Val His Lys Glu Gly
115 120 125
Ser Ser Asn Thr Lys Val Asp Lys Lys Val
130 135
<210> 7
<211> 127
<212> PRT
<213>fusion protein
<400> 7
Ile Thr Gln Gln Asp Leu Ala Pro Gln Gln Arg Ala Ala Pro Gln Gln
1 5 10 15
Lys Arg Ser Ser Pro Ser Glu Gly Leu Cys Pro Pro Gly His His Ile
20 25 30
Ser Glu Asp Gly Arg Asp Cys Ile Ser Cys Lys Tyr Gly Gln Asp Tyr
35 40 45
Ser Thr His Trp Asn Asp Leu Leu Phe Cys Leu Arg Cys Thr Arg Cys
50 55 60
Asp Ser Gly Glu Val Glu Leu Ser Pro Cys Thr Thr Thr Arg Asn Thr
65 70 75 80
Val Cys Gln Cys Glu Glu Gly Thr Phe Arg Glu Glu Asp Ser Pro Glu
85 90 95
Met Cys Arg Lys Cys Arg Thr Gly Cys Pro Arg Gly Met Val Lys Val
100 105 110
Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu Cys Val His Lys Glu
115 120 125
<210> 8
<211> 116
<212> PRT
<213>fusion protein
<400> 8
Ala Ala Pro Gln Gln Lys Arg Ser Ser Pro Ser Glu Gly Leu Cys Pro
1 5 10 15
Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser Cys Lys
20 25 30
Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe Cys Leu
35 40 45
Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro Cys Thr
50 55 60
Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe Arg Glu
65 70 75 80
Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys Pro Arg
85 90 95
Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu Cys
100 105 110
Val His Lys Glu
115
<210> 9
<211> 232
<212> PRT
<213>fusion protein
<400> 9
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
65 70 75 80
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
Claims (7)
1. a kind of application of people sDR5-Fc recombination fusion protein in the drug that preparation treats or prevents pancreatitis, the people
SDR5-Fc recombination fusion protein sequence such as SEQ ID No.1, SEQ ID No.2, SEQ ID No.3 or SEQ ID No.4 institute
Show, or has with SEQ ID No.1, SEQ ID No.2,95% or more homology of SEQ ID No.3 or SEQ ID No.4 simultaneously
Recombination fusion protein with the same function.
2. application according to claim 1, wherein the pancreatitis is selected from acute pancreatitis or chronic pancreatitis.
3. a kind of tumor necrosin relative death inducing ligand antagonist is in the drug that preparation treats or prevents pancreatitis
Using.
4. application according to claim 3, wherein the pancreatitis is selected from acute pancreatitis or chronic pancreatitis.
5. application according to claim 3, the tumor necrosin relative death inducing ligand antagonist is selected from people
SDR5-Fc recombination fusion protein.
6. application according to claim 5, people sDR5-Fc recombination fusion protein sequence such as SEQ ID No.1, SEQ
Shown in ID No.2, SEQ ID No.3 or SEQ ID No.4, or have and SEQ ID No.1, SEQ ID No.2, SEQ ID
95% or more homology of No.3 or SEQ ID No.4 and recombination fusion protein with the same function.
7. a kind of pharmaceutical composition for treating pancreatitis it includes sDR5-Fc recombination fusion protein sequence or encodes the albumen sequence
The nucleotide sequence of column and its pharmaceutically acceptable auxiliary material.
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| CN201710416737.5A CN108992660B (en) | 2017-06-06 | 2017-06-06 | Application of human sDR5-Fc recombinant fusion protein as pancreatitis treatment drug |
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| CN201710416737.5A CN108992660B (en) | 2017-06-06 | 2017-06-06 | Application of human sDR5-Fc recombinant fusion protein as pancreatitis treatment drug |
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| CN108992660B CN108992660B (en) | 2023-04-21 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111450232A (en) * | 2019-01-21 | 2020-07-28 | 中国科学院深圳先进技术研究院 | Application of fusion protein in preparation of medicine for treating hepatitis C |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1621526A (en) * | 2003-11-28 | 2005-06-01 | 中国人民解放军军事医学科学院基础医学研究所 | Recombinant adeno-associated virus for prevention and cure of I-type diabetes and use thereof |
| CN106146670A (en) * | 2015-04-24 | 2016-11-23 | 宜明昂科生物医药技术（上海）有限公司 | A kind of new recombination double functions fusion protein and preparation thereof and application |
| CN106397607A (en) * | 2016-09-13 | 2017-02-15 | 河南师范大学 | Recombinant human fibroblast growth factor 21 fusion protein and application thereof in preparation of medicine for treating metabolic diseases |
-
2017
- 2017-06-06 CN CN201710416737.5A patent/CN108992660B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1621526A (en) * | 2003-11-28 | 2005-06-01 | 中国人民解放军军事医学科学院基础医学研究所 | Recombinant adeno-associated virus for prevention and cure of I-type diabetes and use thereof |
| CN106146670A (en) * | 2015-04-24 | 2016-11-23 | 宜明昂科生物医药技术（上海）有限公司 | A kind of new recombination double functions fusion protein and preparation thereof and application |
| CN106397607A (en) * | 2016-09-13 | 2017-02-15 | 河南师范大学 | Recombinant human fibroblast growth factor 21 fusion protein and application thereof in preparation of medicine for treating metabolic diseases |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111450232A (en) * | 2019-01-21 | 2020-07-28 | 中国科学院深圳先进技术研究院 | Application of fusion protein in preparation of medicine for treating hepatitis C |
| CN111450232B (en) * | 2019-01-21 | 2023-08-01 | 中国科学院深圳先进技术研究院 | Application of fusion protein in preparation of medicine for treating hepatitis C |
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| CN108992660B (en) | 2023-04-21 |
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