CN110448679A - Application of the THBS1 cell factor in preparation treatment liver failure medicament - Google Patents
Application of the THBS1 cell factor in preparation treatment liver failure medicament Download PDFInfo
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- CN110448679A CN110448679A CN201910603549.2A CN201910603549A CN110448679A CN 110448679 A CN110448679 A CN 110448679A CN 201910603549 A CN201910603549 A CN 201910603549A CN 110448679 A CN110448679 A CN 110448679A
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- thbs1
- 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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- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- General Chemical & Material Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses a kind of application of THBS1 cell factor in preparation treatment liver failure medicament, the transport of the medicament of the cell factor of the present invention containing THBS1 and storage temperature are 2 DEG C -8 DEG C, humidity is 45%-75%, THBS1 is one of ABCA superfamily member, and major function is the transmembrane transport for mediating lipid.THBS1 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, it is significant to extend the time-to-live, improve survival rate.
Description
Technical field
The invention belongs to clinical medicine, molecular medicine and fields of biomedicine, are a kind of THBS1 cell factor medicine series
The new technology of liver failure is treated, specifically, being a kind of THBS1 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.Thrombus conglutnin is multi-functional by the secreting type that thrombus conglutnin 1-5 is formed
Protein family.Thrombus conglutnin 1 (THBS1) is first member of the family, is the homologous trimerization glycoprotein of 450kDa, has
Multiple functional domains (1-5).THBS1 is a kind of stroma cell glycoprotein, can be secreted by various kinds of cell type.The ammonia of TBHS1
It works in base terminal domains (NTD) and Heparin-binding, adjusts removal, intake, adherency and the chemotaxis of THBS1.THBS1
Final area be carboxy-terminal domains.The structural domain is in cell adherence, migration, platelet aggregation and adjusting nitric oxide letter
Number conduction in work.By the way that in conjunction with extracellular protein and/or cell surface receptor, THBS1 adjusts various kinds of cell function.
THBS1 plays a significant role in a variety of bioprocess, including angiogenesis, Apoptosis, and potential TGF-β is activated and is immunized
It adjusts.THBS1 further relates to adjust the function of many organs.THBS1 may play a role in a variety of chronic liver diseases, mainly include
Nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma.
THBS1 cell factor has a variety of different hypotypes, the different subtype of THBS1 molecule and in the art reasonable
Deformation, belongs to technical solution of the present invention scope of protection.
Summary of the invention
Exactly in view of the defects existing in the prior art, the new application-THBS1 for providing THBS1 cell factor is thin by the present invention
Application of the intracellular cytokine in preparation treatment liver failure medicament, the present invention is achieved through the following technical solutions:
The invention discloses a kind of application of THBS1 cell factor in the medicament of preparation treatment liver failure.
As further improving, medicament of the present invention includes the pharmaceutically acceptable tax of THBS1 cell factor
Shape 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 THBS1 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 THBS1 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 THBS1 is thin
Intracellular cytokine can be applied in effective preparation treatment liver failure drug, THBS1 cell factor can be cooperated different solvents and
The drug of stabilizer production different dosage forms dosage.In use process selectable administration mode have intravenous injection and intramuscular injection,
Subcutaneous injection takes orally.
In the liver failure course of disease, there are the obstacles of serious metabolic disorder, especially lipid-metabolism.THBS1 cell because
Son can overcome this problem.THBS1 is one of ABCA superfamily member, and major function is the transmembrane transport for mediating lipid.It adjusts
Save the metabolic disorders such as the hepatic cell fattydegeneration during hepatic failure.In addition, it is bad to will appear severe hepatocellular during hepatic failure
Dead and apoptosis, in liver repair process, the mescenchymal stem cell of derived from bone marrow has played important function.THBS1 and mesenchyma
The function of stem cell is related, has therapeutic effect to promotion liver reparation.THBS1 cell factor is in preparation treatment liver failure
In the application of medicament, the biochemical indicator of patient can be significantly improved, reduces bilirubin level, reduces transaminase, improves coagulation function,
Albumin level is improved, hepatocyte death is inhibited, promotes liver cell and bile duct cell regeneration, prevents lethal complication from as above disappearing
Change the big bleeding in road, the generation of serious hepatic encephalopathy and hepatorenal syndrome is significant to extend the time-to-live, improves 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
The invention discloses a kind of application of THBS1 cell factor in the medicament of preparation treatment liver failure, wherein
Medicine type various kinds, technical solution of the present invention is further described below by specific embodiment:
One, the injection of the cell factor containing THBS1
1, the NaCl sterile water solution 1L of configuration 0.9%.(1L specification)
2,0.009mg Tween-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 THBS1 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 THBS1 injection of preparation is dispensed and is saved.
Two, the freeze drying powder injection of the cell factor containing THBS1
1, enough aqua sterilisas are prepared.
2, THBS1 cell factor and proppant (mannitol, sorbierite, dextran etc.) 1:5 ratio are dissolved completely in and go out
Bacterium 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 THBS1 freeze-dried powder of preparation is dispensed and is saved.
Three, the suspension of cell factor containing THBS1 (1000ml)
1,100 grams of THBS1 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 THBS1 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 THBS1 in treatment liver
Failure can substantially reduced hepatic disease degree, improve biochemical indicator, extend the time-to-live, improve survival rate.Therefore, will contain
Medicament of the medicament of THBS1 cell factor for the clinical treatment of liver failure has wide development prospect, becomes treatment
The new method of major Liver disease.
Embodiment 1: big animal (piglet) model of the injection for treating hepatic failure of the cell factor containing THBS1
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-gal 1.5g/kg, causes liver failure model.
Test group: the set time point after D-gal injection is repeatedly injected intravenously THBS1 injection respectively, dosage:
10ml/kg, twice a day.
Control group: injection equivalent is free of the physiological saline of THBS1.
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 87% of piglet of the cell factor containing THBS1,7 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 THBS1, 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 THBS1
Animal model: 100 male rats (200-250 grams) are randomly divided into two groups, every group 50.Every rat abdominal cavity note
D-gal 1.5g/kg is penetrated, liver failure model is made.THBS1 freeze-dried powder and water for injection are configured to suspension.
Test group: THBS1 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 THBS1.
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 90% of the rat of THBS1 treatment group, and 3 days survival rates 65% of control group.By chart
It is bright, compared to the control group, it can significantly extend the life span of rat using the pharmaceutical treatment hepatic failure of the cell factor containing THBS1, mention
High survival rate.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 THBS1
Animal model: 40 bull rabbit (2000-2500 grams) are randomly divided into two groups, every group 20.Every rabbit
Intramuscular injection D-gal 1.5g/kg, is made liver failure model.
Test group: the set time point after D-gal injection gives intramuscular injection THBS1 suspension 20ml respectively, and one day
Twice.
Control group: injection equivalent is free of the physiological saline of THBS1.
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 THBS1 treatment group, 7 days survival rates 80%, and control group 7 days deposit
Motility rate 10%.It is bright by chart, compared to the control group, it can significantly extend house using the pharmaceutical treatment hepatic failure of the cell factor containing THBS1
The life span of rabbit improves survival rate.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 THBS1
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 THBS1 suspension 1ml, and one day two
It is secondary.
Control group: injection equivalent is free of the physiological saline of THBS1.
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 82% of the mouse of THBS1 treatment group, 7 days survival rates 80%, 14 days survival rates
80%, and control group was in 14 days survival rates 16%.It is bright by chart, compared to the control group, controlled using the medicament of the cell factor containing THBS1
The life span of mouse can significantly be extended by treating hepatic failure, improve survival rate.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.THBS1 cell factor in the medicament of preparation treatment liver failure.
- 2. application of the THBS1 cell factor according to claim 1 in the medicament of preparation treatment liver failure, special Sign is that the medicament includes THBS1 cell factor pharmaceutically acceptable excipient, antioxidant and carrier.
- 3. application of the THBS1 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. THBS1 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 THBS1 and storage temperature, humidity is 45%-75%.
- 5. THBS1 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 THBS1 is 15 DEG C -30 DEG C, and humidity is 45%- 75%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910603549.2A CN110448679A (en) | 2019-07-05 | 2019-07-05 | Application of the THBS1 cell factor in preparation treatment liver failure medicament |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910603549.2A CN110448679A (en) | 2019-07-05 | 2019-07-05 | Application of the THBS1 cell factor in preparation treatment liver failure medicament |
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| CN110448679A true CN110448679A (en) | 2019-11-15 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112206313A (en) * | 2020-09-14 | 2021-01-12 | 广州市第一人民医院（广州消化疾病中心、广州医科大学附属市一人民医院、华南理工大学附属第二医院） | Application of LAMA3 or THBS1 in preparation of medicine for promoting liver regeneration |
-
2019
- 2019-07-05 CN CN201910603549.2A patent/CN110448679A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112206313A (en) * | 2020-09-14 | 2021-01-12 | 广州市第一人民医院（广州消化疾病中心、广州医科大学附属市一人民医院、华南理工大学附属第二医院） | Application of LAMA3 or THBS1 in preparation of medicine for promoting liver regeneration |
| CN112206313B (en) * | 2020-09-14 | 2022-02-22 | 广州市第一人民医院（广州消化疾病中心、广州医科大学附属市一人民医院、华南理工大学附属第二医院） | Application of LAMA3 or THBS1 in preparation of medicine for promoting liver regeneration |
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Application publication date: 20191115 |