CN110201149A - Application of the CTSG cell factor in preparation treatment liver failure medicament - Google Patents
Application of the CTSG cell factor in preparation treatment liver failure medicament Download PDFInfo
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- CN110201149A CN110201149A CN201910605534.XA CN201910605534A CN110201149A CN 110201149 A CN110201149 A CN 110201149A CN 201910605534 A CN201910605534 A CN 201910605534A CN 110201149 A CN110201149 A CN 110201149A
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- ctsg
- cell factor
- medicament
- liver failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a kind of application of CTSG cell factor in preparation treatment liver failure medicament, and in the liver failure course of disease, it is largely dead that there are liver cells, and CTSG cell factor can overcome this problem.CTSG N terminal kinase (JNK) is one of family member of MAPK, and JNK access can inhibit the apoptosis of liver cell by the expression of regulation CTSG.CTSG cell factor is in the application of the medicament of preparation treatment liver failure, the biochemical indicator of patient can be significantly improved, bilirubin level is reduced, reduces transaminase, improve coagulation function, albumin level is improved, hepatocyte death is inhibited, promotes liver cell and bile duct cell regeneration, prevent lethal complication such as massive bleeding from upper digestive tract, the generation of serious hepatic encephalopathy and hepatorenal syndrome, significantly extension patient survival, improve survival rate.
Description
Technical field
The invention belongs to clinical medicine, molecular medicine and fields of biomedicine, are a kind of CTSG cell factor medicine series
The new technology of liver failure is treated, specifically, being a kind of CTSG cell factor in preparation treatment liver failure medicament
Application.
Background technique
Liver failure is the disease of liver large area caused by necrosis caused by a kind of a variety of causes, and the state of an illness is dangerous, patient
Dead more than in a short time, customary medical complex treatment case fatality rate is up to 50%-90%.In addition to orthotopic liver transplantation, still lack at present
Specificity therapeutic method.But due to serious for liver shortage, a large amount of patients die during waiting liver transfer operation.Specify liver function
The pathogenesis of energy failure carries out early treatment to for mechanism, can be effectively blocked disease progression, case fatality rate reduced, to liver
Functional failure treatment is extremely important.
Cathepsin G (CTSG) is one of the member of serine stretch protein enzyme family, is found in neutrophil leucocyte earliest
In neutrophil granular and other myeloid cells, including B cell, primary person monocytic cell, marrow sample Dendritic Cells, slurry are carefully
Born of the same parents' sample Dendritic Cells and mouse microglia.When above-mentioned cell is stimulated, CTSG be released to extracellular space or
It is integrated to cell surface.Importantly, the CTSG of purifying changes cytoskeleton by cutting vessel endothelium cadherin, increase
The chemotaxis of inflammatory cell, to increase the permeability of endothelial cell and epithelial cell.
AMPH cell factor have a variety of different hypotype structures, the reasonable deformation of amino acid sequence in the art,
Belong to technical solution of the present invention scope of protection.
Summary of the invention
The present invention exactly in view of the defects existing in the prior art, provides new application-CTSG cell of CTSG cell factor
Application of the factor in preparation treatment liver failure medicament, the present invention is achieved through the following technical solutions:
The invention discloses a kind of application of CTSG cell factor in the medicament of preparation treatment liver failure.
As further improving, medicament of the present invention includes CTSG cell factor pharmaceutically acceptable figuration
Agent, antioxidant and carrier.
As a further improvement, the form of medicament of the present invention is injection or freeze drying powder injection or suspension.
As a further improvement, the transport of the medicament of the cell factor of the present invention containing CTSG and storage temperature are 2
DEG C -8 DEG C, humidity is 45%-75%.
As a further improvement, the application temperature of the medicament of the cell factor of the present invention containing CTSG is 15 DEG C -30
DEG C, humidity is 45%-75%.
Compared with prior art, beneficial effects of the present invention are as follows:
The present invention is based on multicenter, perspective big cohort crowd and samples, using transcript profile sequencing, multiple groups association point
The multiple technologies method such as verifying in analysis, qRT-PCR and zoopery body, carries out cross validation from different perspectives, and discovery CTSG is thin
Intracellular cytokine can be applied in effective preparation treatment liver failure drug, and CTSG cell factor can be cooperated to different solvents and steady
Determine the drug of agent production different dosage forms dosage.Selectable administration mode has intravenous injection and intramuscular injection, skin in use process
Lower injection takes orally.
In the liver failure course of disease, it is largely dead that there are liver cells, and CTSG cell factor can overcome this problem.CTSG
N terminal kinase (JNK) is one of family member of MAPK, and JNK access can inhibit liver thin by the expression of regulation CTSG
The apoptosis of born of the same parents.In addition, will appear serious liver metabolism dysfunction during hepatic failure, liver and other devices is further aggravated
Official's damage.CTSG has played key effect in lipid-metabolism, and some researches show that, CTSG shortage type newborn mices after birth not
Occurs serious lipodystrophy long.CTSG cell factor, can in the application of the medicament of preparation treatment liver failure
The biochemical indicator of patient is significantly improved, bilirubin level is reduced, reduces transaminase, improves coagulation function, improves albumin level,
Inhibit hepatocyte death, promotes liver cell and bile duct cell regeneration, prevent lethal complication such as massive bleeding from upper digestive tract, seriously
The generation of hepatic encephalopathy and hepatorenal syndrome, significantly extension patient survival, improve survival rate.
Detailed description of the invention
Fig. 1 is experimental group and control group piglet time-survivor curve schematic diagram；
Fig. 2 is experimental group and control rats time-survivor curve schematic diagram；
Fig. 3 is experimental group and control group rabbit time-survivor curve schematic diagram；
Fig. 4 is experimental group and control group mice time-survivor curve schematic diagram.
Specific embodiment
It is therein the invention discloses a kind of application of CTSG cell factor in the medicament of preparation treatment liver failure
Medicine type various kinds is further described technical solution of the present invention below by specific embodiment:
One, the injection of the cell factor containing CTSG
1, the NaCl sterile water solution 1L of configuration 0.9%.(1L specification)
2,0.009mgTween-80 is added in 0.9% NaCl sterile water solution of 50% full dose volume.
3, the amber acid gelatin of 80ml is added in the solution that 2 steps are configured.
4, the CTSG cell factor of prescribed dose is added in the solution that 3 steps are configured.
5, pH value is adjusted between 5.0-7.0 with the HCl of 0.1mol/L.
6,0.9% NaCl sterile water solution is settled to full dose.
7, the CTSG injection of preparation is dispensed and is saved.
Two, the freeze drying powder injection of the cell factor containing CTSG
1, enough aqua sterilisas are prepared.
2, CTSG cell factor and proppant (mannitol, sorbierite, dextran etc.) 1:5 ratio are dissolved completely in sterilizing
Water.
3, the HCl of 0.1mol/L adjusts 2 step solution ph between 5.0-7.0.
4,3 step solution are put into freeze dryer, freeze-drying.- 40 DEG C freeze 6 hours, and -40-0 DEG C of vacuum freeze dryings 24 are small
When, freeze-dried powder is made in 2 hours in 20 DEG C of dryings.
5, the CTSG freeze-dried powder of preparation is dispensed and is saved.
Three, the suspension of cell factor containing CTSG (1000ml)
1,100 grams of CTSG cell factors are ground into the particle of 5-10 microns of sizes.
2,30g PVP K-30 (PvP) is dissolved in 1000ml aqua sterilisa, prepares solution.
3, the CTSG cell factor particle that 100g is crushed is added in solution prepared by step 2.
4, it is adjusted between pH value 6.0-7.0 using dilute hydrochloric acid solution and diluted sodium hydroxide solution.
5, it is mixed 1 hour in liquid flash mixer with 3500 revs/min.
6, the suspension prepared is dispensed and is saved.
Technical solution of the present invention is further described by specific embodiment and comparative example below according to attached drawing:
The present invention is proved by a variety of different animals model tests, using the medicament of the cell factor containing CTSG in treatment liver failure
Exhaust can substantially reduced hepatic disease degree, improve biochemical indicator, extend the time-to-live, improve survival rate.Therefore, will to contain CTSG thin
Medicament of the medicament of intracellular cytokine for the clinical treatment of liver failure has wide development prospect, becomes treatment major Liver
The new method of disease.
Embodiment 1: big animal (piglet) model of the injection for treating hepatic failure of the cell factor containing CTSG
Animal model: 30 male Chinese experimentals are randomly divided into two groups, every group 15 with piglet (8-10 kilograms).Every children
Pig jugular vein injects D-gal1.5g/kg, causes liver failure model.
Test group: the set time point after D-gal injection is repeatedly injected intravenously CTSG injection respectively, dosage: 10ml/
Kg, twice a day.
Control group: injection equivalent is free of the physiological saline of CTSG.
Control group and experimental group do not receive other drugs and control.
Fig. 1 is experimental group and control group piglet time-survivor curve schematic diagram, illustrates experimental group and control group piglet
Survival rate.The results show that pharmaceutical treatment group 3 days survival rates 93% of piglet of the cell factor containing CTSG, 7 days survival rates 80%, 14
Its survival rate 80% simultaneously reaches survival steady in a long-term.And control group is in all dead in 2 weeks.It can be seen that compared to the control group, benefit
The life span of piglet can significantly be extended with the pharmaceutical treatment hepatic failure of the cell factor containing CTSG, improve survival rate.Illustrate this hair
It is bright to have a clear superiority.
Embodiment 2: toy (rat) model of the freeze drying powder injection treatment hepatic failure of the cell factor containing CTSG
Animal model: 100 male rats (200-250 grams) are randomly divided into two groups, every group 50.Every rat abdominal cavity note
D-gal1.5g/kg is penetrated, liver failure model is made.CTSG freeze-dried powder and water for injection are configured to suspension.
Test group: CTSG freeze-dried powder suspension 4ml is injected intraperitoneally in the set time point after D-gal injection respectively,
Twice a day.
Control group: injection equivalent is free of the physiological saline of CTSG.
Control group and experimental group do not receive other drugs treatment.
Fig. 2 is that experimental group and control rats time-survivor curve schematic diagram, Fig. 2 illustrate experimental group and control rats
Survival rate: the results show that 3 days survival rates 96% of the rat of CTSG treatment group, 7 days survival rates 94%, 14 days survival rates 94%,
And control group was in 14 days survival rates 24%.It is bright by chart, compared to the control group, utilize the pharmaceutical treatment liver failure of the cell factor containing CTSG
The life span that can significantly extend rat is exhausted, survival rate is improved.Illustrate that the present invention has a clear superiority.
Embodiment 3: the Rabbit Model of the suspension treatment liver failure of the cell factor containing CTSG
Animal model: 40 bull rabbit (2000-2500 grams) are randomly divided into two groups, every group 20.Every rabbit
Liver failure model is made in intramuscular injection D-gal1.5g/kg.
Test group: the set time point after D-gal injection gives intramuscular injection CTSG suspension 20ml respectively, and one day two
It is secondary.
Control group: injection equivalent is free of the physiological saline of CTSG.
Control group and experimental group do not receive other drugs treatment.
Fig. 3 is that experimental group and control group rabbit time-survivor curve schematic diagram, Fig. 3 illustrate experimental group and control group rabbit
Survival rate: the results show that 1 day survival rate 90% of the rabbit of CTSG treatment group, 7 days survival rates 90%, 14 days survival rates 90%,
And control group was in 14 days survival rates 20%.It is bright by chart, compared to the control group, utilize the pharmaceutical treatment liver failure of the cell factor containing CTSG
The life span that can significantly extend rabbit is exhausted, survival rate is improved.Illustrate that the present invention has a clear superiority.
Embodiment 4: the mouse model of the suspension treatment liver failure of the cell factor containing CTSG
Animal model: 100 adult male mices (20-25 grams) are randomly divided into two groups, every group 50.Every mouse muscle
Inject CCl4, liver failure model is made.
Test group: respectively in CCl4Set time point after injection is injected intraperitoneally CTSG suspension 1ml, and one day two
It is secondary.
Control group: injection equivalent is free of the physiological saline of CTSG.
Control group and experimental group do not receive other drugs treatment.
Fig. 4 is that experimental group and control group mice time-survivor curve schematic diagram, Fig. 4 illustrate experimental group and control group mice
Survival rate: the results show that 3 days survival rates 86% of the mouse of CTSG treatment group, 7 days survival rates 86%, 14 days survival rates 86%,
And control group was in 14 days survival rates 24%.It is bright by chart, compared to the control group, utilize the pharmaceutical treatment liver failure of the cell factor containing CTSG
The life span that can significantly extend mouse is exhausted, survival rate is improved.Illustrate that the present invention has a clear superiority.
Exemplified as above is only the preferred embodiment of the present invention, and the present invention is not limited to above embodiments, this field skills
The oher improvements and changes that art personnel directly export or associate without departing from the spirit and concept in the present invention, should all
Think to be included within the scope of the present invention.
Claims (5)
- Application of the 1.CTSG cell factor in the medicament of preparation treatment liver failure.
- 2. application of the CTSG cell factor according to claim 1 in the medicament of preparation treatment liver failure, special Sign is that the medicament includes CTSG cell factor pharmaceutically acceptable excipient, antioxidant and carrier.
- 3. application of the CTSG cell factor according to claim 2 in the medicament of preparation treatment liver failure, special Sign is that the form of the medicament is injection or freeze drying powder injection or suspension.
- 4. CTSG cell factor according to claim 1 or 2 or 3 answering in the medicament of preparation treatment liver failure It is 2 DEG C -8 DEG C with, which is characterized in that the transport of the medicament of the cell factor containing CTSG and storage temperature, humidity is 45%- 75%.
- 5. CTSG cell factor according to claim 1 or 2 or 3 answering in the medicament of preparation treatment liver failure With, which is characterized in that the application temperature of the medicament of the cell factor containing CTSG is 15 DEG C -30 DEG C, and humidity is 45%- 75%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910605534.XA CN110201149A (en) | 2019-07-05 | 2019-07-05 | Application of the CTSG cell factor in preparation treatment liver failure medicament |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910605534.XA CN110201149A (en) | 2019-07-05 | 2019-07-05 | Application of the CTSG cell factor in preparation treatment liver failure medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110201149A true CN110201149A (en) | 2019-09-06 |
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ID=67796483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910605534.XA Withdrawn CN110201149A (en) | 2019-07-05 | 2019-07-05 | Application of the CTSG cell factor in preparation treatment liver failure medicament |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110201149A (en) |
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2019
- 2019-07-05 CN CN201910605534.XA patent/CN110201149A/en not_active Withdrawn
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Application publication date: 20190906 |
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