CN114644683B - Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof - Google Patents
Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof Download PDFInfo
- Publication number
- CN114644683B CN114644683B CN202210357404.0A CN202210357404A CN114644683B CN 114644683 B CN114644683 B CN 114644683B CN 202210357404 A CN202210357404 A CN 202210357404A CN 114644683 B CN114644683 B CN 114644683B
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- apoptosis
- liver
- application
- hepatocyte
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/067—Hepatocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The application relates to a polypeptide and application thereof, in particular to a polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof. The amino acid sequence of the polypeptide for promoting the proliferation of the liver cells and/or inhibiting the apoptosis of the liver cells is at least one of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5 and SEQ ID NO. 6. The polypeptide has the activity of promoting the proliferation of liver cells and/or inhibiting the apoptosis of liver cells, which is equivalent to or better than HIP/PAP, and has the advantages of small molecular weight, easy synthesis, low immunogenicity and the like, so that the polypeptide has wide application prospect.
Description
Filing date of the original divisional application: 2018, 09, 18;
application number of the original divisional application: 2021107606690;
title of the original divisional application: a polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and use thereof;
the original divisional application is the divisional application of the parent application:
filing date of the parent application: 2018, 09, 18;
application number of the parent application: 2018110919805;
title of the parent application: a polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and use thereof; the present application is re-filed application of the applicant to the original filed application according to the examination opinion of the examiner.
Technical Field
The application relates to a polypeptide and application thereof, in particular to a polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof.
Background
The liver is the largest internal organ in the human body (approximately 2.5% of the total mass of the human body) and is also the central metabolic organ. The main cells that perform liver function are parenchymal cells, which account for 80% of the total liver cells. Hepatocytes exert a range of effects including plasma production, carrier protein synthesis, detoxification of digestive products, conjugation, secretion of hormones, regulation of blood lipid and amino acid synthesis and metabolism, and the like.
Apoptosis (apoptosis) is the active suicide process of cells in a specific environment. Apoptosis is two distinct patterns of apoptosis and death observed in Kerr et al 1972 when studying liver ischemia. Apoptosis is characterized by shrinkage of cells, cellular membrane as a cell-like protrusion, formation of apoptotic bodies, degradation of nuclear fragments and nuclear DNA, and other abnormal phenomena. Apoptosis is a major feature of many clinical pathological changes, especially in liver diseases, and liver apoptosis is an important factor causing liver damage. Apoptosis plays an important role in the pathogenesis of liver disease, and disorders of the death receptor pathway are thought to be one of the important causes of triggering the occurrence of acute/chronic liver injury. Recent studies have shown that apoptosis of liver cells is widely involved in the pathological processes of various liver diseases including liver failure, viral hepatitis, liver fibrosis, cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, and the like.
Liver Failure (LF) is a serious liver injury caused by various factors such as viruses, medicines, alcohol and the like, so that serious disorder or decompensation occurs to functions such as detoxification, excretion, synthesis and the like, a group of clinical syndrome mainly represented by coagulation dysfunction, severe jaundice, ascites, hepatic encephalopathy, even gastrointestinal hemorrhage and the like occurs, and the disease mortality is extremely high, so that the liver failure is one of critical symptoms common in clinical practice in hepatology. Liver failure is classified into acute liver failure (acute liver failure, ALF), subacute liver failure (subacute liver failure, SALF), chronic acute (subacute) liver failure (acute-on-chronic liver failure, ACLF) and chronic liver failure (chronic liver failure, CLF) according to the pathological features and disease progression of 2012 edition of the guidelines for liver failure. Liver failure is a critical clinical symptom, and has no definite specific medicine for treating the acute symptom, so that the liver failure becomes one of the worldwide refractory diseases, and although artificial liver and liver transplantation are effective treatment methods, the treatment methods cannot be widely popularized and used in China due to the expensive cost, shortage of liver sources, rejection and the like.
The human HIP/PAP protein, also known as the neogenin 3 alpha (Regenerating islet-derived protein III-alpha), is a protein consisting of 165 amino acids secreted by the pancreas. Research shows that HIP/PAP protein can protect liver cells from tumor necrosis factor mediated programmed death, and is also one mitogen capable of promoting mitosis of liver cells and thus promoting liver cell regeneration. Currently, human HIP/PAP proteins are generally expressed by recombinant expression systems (e.g., E.coli), and the purification methods are complex and the preparation costs are high.
Polypeptides are compounds formed from multiple amino acids by the dehydration condensation of the amino group of one amino acid with the carboxyl group of another amino acid, which may also be derived from proteolytic intermediates. Polypeptides generally refer to compounds formed by the dehydration condensation of less than 50 amino acids, while polypeptides of more than 50 amino acids are commonly referred to as proteins. The polypeptide medicine has the characteristics of small molecular weight, easy synthesis, small side effect, strong specificity and the like, and rarely causes serious immune response.
Disclosure of Invention
The application aims to overcome the defects of the prior art and provide a polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof.
In order to achieve the above purpose, the technical scheme adopted by the application is as follows: the polypeptide for promoting the proliferation of liver cells and/or inhibiting the apoptosis of liver cells has an amino acid sequence selected from at least one of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5 and SEQ ID NO. 6.
The polypeptide for promoting the proliferation of liver cells and/or inhibiting the apoptosis of liver cells can be any polypeptide shown in any one amino acid sequence of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5 and SEQ ID NO. 6, or can be a combination of any two or more (including two) polypeptides in the 6 polypeptides.
The polypeptides shown in SEQ ID NO. 1-SEQ ID NO. 6 are derived from human HIP/PAP proteins. The inventors found in a large number of studies that most polypeptide fragments derived from human HIP/PAP proteins are not biologically active, but unexpectedly found that the polypeptides shown in SEQ ID No. 1-SEQ ID No. 6 have activities that are equivalent or superior to HIP/PAP in promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis.
As a preferred embodiment of the polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis, the amino acid sequence of the polypeptide is shown in SEQ ID NO. 4. Studies show that in the polypeptides shown as SEQ ID NO. 1-SEQ ID NO. 6 and HIP/PAP, the polypeptide shown as SEQ ID NO. 4 has the strongest effect of promoting liver cell proliferation and inhibiting liver cell apoptosis, and the activity of the polypeptide is obviously higher than that of HIP/PAP.
In addition, the application also provides application of the polypeptide in preparing a product for promoting liver cell proliferation or treating diseases caused by liver cell apoptosis.
As a preferred embodiment of the use according to the application, the product is a medicament.
As a preferred embodiment of the use according to the application, the medicament is in a liquid dosage form.
As a preferred embodiment of the use according to the present application, the promotion of hepatocyte proliferation is in vivo promotion of liver regeneration or in vitro promotion of hepatocyte growth.
As a preferred embodiment of the use according to the present application, the disease caused by apoptosis of liver cells is liver failure, viral hepatitis, liver fibrosis, cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease or autoimmune liver disease. More preferably, the liver failure is acute liver failure.
The in vitro cell experiments prove that the polypeptide shown in SEQ ID NO. 1-SEQ ID NO. 6 has the activity of promoting the proliferation of liver cells and inhibiting the apoptosis of liver cells, so that the polypeptide can be used for promoting the proliferation of liver cells or treating diseases caused by the apoptosis of liver cells. Studies have shown that diseases of hepatocyte apoptosis include liver failure, viral hepatitis, cholestatic liver injury, alcoholic liver injury, nonalcoholic steatohepatitis, cirrhosis, and toxin-or drug-mediated liver injury, etc., and the polypeptides of the present application can be used for treating the above diseases because they have an activity of inhibiting hepatocyte apoptosis. The polypeptide of the application shows good treatment effect on acute liver failure in an animal model of acute liver failure, and further proves that the polypeptide can be used for treating liver cell apoptosis related diseases.
Finally, the application also provides a medicament for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis, wherein the medicament contains the polypeptide.
As a preferred embodiment of the medicament for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis according to the application, the medicament further comprises a pharmaceutically acceptable carrier. Those skilled in the art can routinely select pharmaceutically acceptable carriers depending on the dosage form of the drug and the like. Dosage forms of the medicament include, but are not limited to, liquid dosage forms, gaseous dosage forms, solid dosage forms, etc., and as a preferred embodiment of the medicament for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis according to the application, the medicament is in liquid dosage form. The medicament of the present application may be administered by intravenous injection or subcutaneous injection.
As a preferred embodiment of the medicament for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis according to the application, the promotion of hepatocyte proliferation is in vivo promotion of liver regeneration or in vitro promotion of hepatocyte growth.
Compared with the prior art, the application has the beneficial effects that: the application provides polypeptides for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis, which have the length of 9 to 27 amino acids, and the length of HIP/PAP protein is 165 amino acids, the length of the polypeptide is obviously shorter than that of the HIP/PAP protein, but has the activity of promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis, which is equivalent to or better than that of the HIP/PAP, and the polypeptide has the advantages of small molecular weight, easy synthesis, low immunogenicity and the like, so the polypeptide has wide application prospect.
Drawings
FIG. 1 is a graph showing the comparison of the activity of the polypeptide of the present application with HIP/PAP in promoting hepatocyte proliferation;
FIG. 2 is a graph showing the comparison of the survival rate of the polypeptide of the present application with that of HIP/PAP treated mice with acute liver failure.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present application, the present application will be further described with reference to the accompanying drawings and specific examples.
Example 1 polypeptide
An example of a polypeptide of the present application that promotes hepatocyte proliferation and/or inhibits hepatocyte apoptosis is shown in table 1.
TABLE 1
The polypeptide of the embodiment is synthesized by Shenzhen Hongzhen Co., ltd. By adopting a solid phase synthesis process, the purity is more than 98%, and the synthesized purity is 50mg.
Example 2 detection of in vitro Activity to promote hepatocyte proliferation
In this example, human hepatocyte line HL-7702 was purchased from ATCC.
The method for detecting the activity of 6 polypeptides and HIP/PAP in vitro for promoting hepatocyte proliferation described in example 1 comprises the following steps:
and taking out frozen HL-7702 cells, and thawing and recovering the frozen HL-7702 cells in a water bath kettle at the temperature of 37 ℃. Centrifuging at 800rpm on a low speed centrifuge for 5 minutes; the supernatant was aspirated and the cells were resuspended in 1ml of medium.
The resuspended cells are transferred to a new culture flask, and a proper amount of MEM is added for cultureNourishing Medium, CO 2 Incubator culture (culture conditions 5% CO) 2 Saturated humidity, 37 ℃).
After the cells grow to 80%, the cells are blown up and counted after the cells are digested, and the cell concentration is adjusted to be 1 multiplied by 10 5 Mu.l/ml, added to 96-well plates, per well, i.e.1X 10 cells per well 4 And each.
After cell attachment, different drugs were added, IGL9, PTQ9, LHD9, SLS27, AYG, VSV19, HIP/PAP, at two concentrations (1. Mu.g/ml, 10. Mu.g/ml) for each drug, and PBS was used as a negative control.
After 0, 2, 3, 4 and 5 days of drug treatment, cell proliferation assay reagents (Promega, cat. No. G3582) were added in a 1/10 ratio. That is, 100. Mu.l of the culture medium was added with 10. Mu.l of the detection solution.
After 4 hours incubation, plates were read with an microplate reader and OD490 data was measured.
As a result, as shown in FIG. 1, it is apparent from FIG. 1 that HIP/PAP and the polypeptide of the present application have effects of promoting hepatocyte proliferation, and the dose-effect relationship is remarkable, and the activities of the 6 polypeptides of the present application are equivalent to or better than HIP/PAP, wherein SLS27 has the strongest effect of promoting hepatocyte proliferation.
Example 3 detection of in vitro Activity to inhibit apoptosis of hepatocytes
The method for detecting the activity of the 6 polypeptides in example 1 and HIP/PAP in vitro to inhibit hepatocyte apoptosis in this example comprises the following steps:
human liver cell HL-7702 is spread into 96-well plate with cell concentration of 1×10 5 100 μl/well, i.e. 1×10 cells/well 4 And each.
An apoptosis model was established by adding 20ng/mL Act D2 to each well for 30min and 80ng/mL TNF-. Alpha.for 48 h.
Corresponding drug treatments, IGL9, PTQ9, LHD9, SLS27, AYG, VSV19, HIP/PAP, were added in 10. Mu.l volumes, two concentrations of each drug (final concentration 1. Mu.g/ml, 10. Mu.g/ml, respectively) were added in 10. Mu.l volumes, and the same volume of PBS was used as negative control.
After 24h of drug treatment, 100. Mu.l of Caspase-Glo cube reagent (Caspase-Glo cube 3/7 Assay promega Co., ltd.; cat. No. G8090) was added to each well, and the contents of each well were gently mixed on a plate shaker at a speed of 300-500rpm for about 30 seconds. Incubation was carried out at room temperature (18-22 ℃) for 30 minutes to 3 hours.
The fluorescence value of each sample was measured on a fluorescence Luminometer (Promega, gloMax bioluminescence detector).
As a result, HIP/PAP and the polypeptides of the application have the effect of inhibiting the apoptosis of liver cells, and the quantity and effect relationship is obvious, and the activity of the 6 polypeptides of the application is equivalent to or better than HIP/PAP, wherein the effect of SLS27 on inhibiting the apoptosis of liver cells is strongest.
Example 4 detection of the Effect of treating acute liver failure in animal models
The method for detecting the effect of the 6 polypeptides in the embodiment 1 and HIP/PAP on treating acute liver failure comprises the following steps:
the highest activity polypeptide SLS27 in examples 2 and 3 was selected for in vivo activity studies to examine the therapeutic effect on the mouse acute liver failure model.
80 male BALB/C mice at 8 weeks of age were randomly divided into four groups, which were normal control group, negative control group, SLS 27-treated group and HIP/PAP-treated group, and physiological saline, SLS27 polypeptide (2.5 mg/kg) and HIP/PAP (2.5 mg/kg) were administered by tail vein injection in an injection volume of 100. Mu.l. After 2. 2D, 5% of D-galactosamine (D-Gal, sigma) is administered to establish an acute liver failure model, and normal control group is administered with the same amount of physiological saline at a dose of 1.0 g/kg.
After the mice are injected with D-Gal for 6 hours, the mice in the negative control group begin to have the phenomena of activity reduction and diet reduction, and the normal control group and SLS27 and HIP/PAP treatment groups have no obvious change; 48 After h, the mice in the negative control group had significantly reduced activity and started to die, with a mortality rate of 100% within 96 h. After 168h (7 days) treatment, the normal control mice survived 100%, the SLS27 treated mice survived 60% and the HIP/PAP treated mice survived 40% respectively, and the negative control mice survived 0. The animal survival rate of the SLS27 treated group was significantly higher (P < 0.01) compared to the negative control group and was superior to the HIP/PAP group, indicating that the activity of the SLS27 polypeptide was higher than HIP/PAP (see fig. 2).
Finally, it should be noted that the above embodiments are only for illustrating the technical solution of the present application and not for limiting the scope of the present application, and although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present application may be modified or substituted equally without departing from the spirit and scope of the technical solution of the present application.
SEQUENCE LISTING
<110> Guangzhou Zhencheng medical science and technology Co., ltd
<120> polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and use thereof
<160> 6
<170> PatentIn version 3.3
<210> 1
<211> 9
<212> PRT
<213> Synthesis
<400> 1
Ile Gly Leu His Asp Pro Thr Gln Gly
1 5
<210> 2
<211> 9
<212> PRT
<213> Synthesis
<400> 2
Pro Thr Gln Gly Thr Glu Pro Asn Gly
1 5
<210> 3
<211> 9
<212> PRT
<213> Synthesis
<400> 3
Leu His Asp Pro Thr Gln Gly Thr Glu
1 5
<210> 4
<211> 27
<212> PRT
<213> Synthesis
<400> 4
Ser Leu Ser Arg Ser Thr Ala Phe Leu Arg Trp Lys Asp Tyr Asn Cys
1 5 10 15
Asn Val Arg Leu Pro Tyr Val Cys Lys Phe Thr
20 25
<210> 5
<211> 25
<212> PRT
<213> Synthesis
<400> 5
Ala Tyr Gly Ser His Cys Tyr Ala Leu Phe Leu Ser Pro Lys Ser Trp
1 5 10 15
Thr Asp Ala Asp Leu Ala Cys Gln Lys
20 25
<210> 6
<211> 19
<212> PRT
<213> Synthesis
<400> 6
Val Ser Val Leu Ser Gly Ala Glu Gly Ser Phe Val Ser Ser Leu Val
1 5 10 15
Lys Ser Ile
Claims (4)
1. The polypeptide for promoting hepatocyte proliferation is characterized in that the amino acid sequence of the polypeptide is SEQ ID NO. 1.
2. A medicament for promoting hepatocyte proliferation, comprising the polypeptide of claim 1.
3. The drug for promoting hepatocyte proliferation of claim 2, wherein the drug is in a liquid dosage form.
4. The hepatocyte proliferation promoting agent of claim 2, wherein the promotion of hepatocyte proliferation is in vitro promotion of increased hepatocyte numbers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210357404.0A CN114644683B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210357404.0A CN114644683B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN201811091980.5A CN109439612B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811091980.5A Division CN109439612B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114644683A CN114644683A (en) | 2022-06-21 |
| CN114644683B true CN114644683B (en) | 2023-09-12 |
Family
ID=65532993
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210358219.3A Active CN114702551B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202110760669.0A Active CN113307845B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202210357404.0A Active CN114644683B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202210358220.6A Active CN114621324B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN201811091980.5A Active CN109439612B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202210357405.5A Active CN114702550B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210358219.3A Active CN114702551B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202110760669.0A Active CN113307845B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210358220.6A Active CN114621324B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN201811091980.5A Active CN109439612B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
| CN202210357405.5A Active CN114702550B (en) | 2018-09-18 | 2018-09-18 | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (6) | CN114702551B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110669126B (en) * | 2019-10-23 | 2022-08-16 | 广州领晟医疗科技有限公司 | Polypeptide GPR5 and application thereof in promoting hepatocyte proliferation and inhibiting hepatocyte apoptosis |
| CN110627866B (en) * | 2019-10-23 | 2022-10-18 | 广州领晟医疗科技有限公司 | Polypeptide RLY4 and application thereof in promoting liver regeneration and inhibiting hepatocyte apoptosis |
| CN110713521B (en) * | 2019-10-23 | 2022-08-16 | 广州领晟医疗科技有限公司 | Polypeptide CAK18N and application thereof in promoting liver regeneration and inhibiting hepatocyte apoptosis |
| CN110903381B (en) * | 2019-12-04 | 2022-08-16 | 广州领晟医疗科技有限公司 | Peptide KAI11 for promoting cartilage regeneration and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1835764A (en) * | 2003-06-18 | 2006-09-20 | 国立健康与医学研究所 | Hip/pap polypeptide composition for use in liver regeneration and for the prevention of liver failure |
| CN1896100A (en) * | 2005-06-01 | 2007-01-17 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Liver regenerated factor and its use |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014139182A1 (en) * | 2013-03-15 | 2014-09-18 | Shenzhen Hightide Biopharmaceutical, Ltd. | Compositions and methods of using islet neogenesis peptides and analogs thereof |
| CN104650212A (en) * | 2013-03-15 | 2015-05-27 | 深圳君圣泰生物技术有限公司 | Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives |
| CN104045698B (en) * | 2013-03-15 | 2019-04-16 | 深圳君圣泰生物技术有限公司 | A kind of polypeptide, polypeptide derivative, the officinal salt of polypeptide and pharmaceutical composition |
| CN104592380A (en) * | 2013-03-15 | 2015-05-06 | 深圳君圣泰生物技术有限公司 | Polypeptide, derivative of polypeptide, pharmaceutical salt of polypeptide, pharmaceutical composition and application of polypeptide or derivative of polypeptide |
| CN104650211A (en) * | 2013-03-15 | 2015-05-27 | 深圳君圣泰生物技术有限公司 | Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives |
| CN106749606B (en) * | 2016-12-29 | 2018-06-22 | 广州领晟医疗科技有限公司 | A kind of peptide for repairing cartilage and/or treating osteoarthritis |
| CN107936111B (en) * | 2017-12-16 | 2021-09-07 | 广州安辰新药研究院有限公司 | Preparation method of HIP/PAP protein |
-
2018
- 2018-09-18 CN CN202210358219.3A patent/CN114702551B/en active Active
- 2018-09-18 CN CN202110760669.0A patent/CN113307845B/en active Active
- 2018-09-18 CN CN202210357404.0A patent/CN114644683B/en active Active
- 2018-09-18 CN CN202210358220.6A patent/CN114621324B/en active Active
- 2018-09-18 CN CN201811091980.5A patent/CN109439612B/en active Active
- 2018-09-18 CN CN202210357405.5A patent/CN114702550B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1835764A (en) * | 2003-06-18 | 2006-09-20 | 国立健康与医学研究所 | Hip/pap polypeptide composition for use in liver regeneration and for the prevention of liver failure |
| CN1896100A (en) * | 2005-06-01 | 2007-01-17 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Liver regenerated factor and its use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113307845A (en) | 2021-08-27 |
| CN114644683A (en) | 2022-06-21 |
| CN109439612B (en) | 2021-09-21 |
| CN114621324A (en) | 2022-06-14 |
| CN109439612A (en) | 2019-03-08 |
| CN113307845B (en) | 2022-05-24 |
| CN114702550A (en) | 2022-07-05 |
| CN114621324B (en) | 2023-09-12 |
| CN114702551B (en) | 2023-09-12 |
| CN114702550B (en) | 2023-09-12 |
| CN114702551A (en) | 2022-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114644683B (en) | Polypeptide for promoting hepatocyte proliferation and/or inhibiting hepatocyte apoptosis and application thereof | |
| JP2020007372A (en) | Peptide with anti-obesity and anti-diabetes activity and use thereof | |
| JPH11504036A (en) | Chemokine binding proteins and uses thereof | |
| CN110713521B (en) | Polypeptide CAK18N and application thereof in promoting liver regeneration and inhibiting hepatocyte apoptosis | |
| CN113499426B (en) | Application of milk-derived polypeptide in preparation of medicines, health products or food additives for preventing and treating alcoholic fatty liver disease | |
| CN111135311B (en) | Use of ECM1 for the prevention and/or treatment of liver fibrosis related diseases | |
| CN110669126B (en) | Polypeptide GPR5 and application thereof in promoting hepatocyte proliferation and inhibiting hepatocyte apoptosis | |
| US20240041988A1 (en) | Use of elapidae postsynaptic neurotoxin in the treatment of over expression of inflammatory cytokines related diseases | |
| CN113508126B (en) | Novel peptides and uses thereof | |
| CN103848914B (en) | A kind of the Bufrudin polypeptide and preparation method thereof and purposes of tool anticoagulating active | |
| CN110627866B (en) | Polypeptide RLY4 and application thereof in promoting liver regeneration and inhibiting hepatocyte apoptosis | |
| WO1998024467A1 (en) | Remedies for fulminant hepatitis | |
| JP5549912B2 (en) | Drugs for polycythemia vera or essential thrombocythemia | |
| CN111249446B (en) | New use of polypeptide and its salt | |
| CN112675292B (en) | Use of probiotic-containing formulations for the treatment of diseases | |
| CN116478243B (en) | Application of schistosome-derived peptide in preventing and treating metabolic diseases | |
| CN116836233B (en) | Anti-inflammatory active polypeptide and application thereof | |
| RU2783776C1 (en) | New peptide and application thereof | |
| JPH05178756A (en) | Preventing and treating agent for hepatopathy | |
| JPH06219963A (en) | Pharmaceutical containing reg protein as active component | |
| CN116836296A (en) | Fusion protein of alpha melanocyte stimulating hormone, preparation method and application thereof | |
| CN101041066B (en) | The application of r-sHSA for treating chronic liver disease | |
| CN117720664A (en) | Artificial peptidomimetic dimer, preparation method thereof and application thereof in preparation of anti-gouty arthritis drugs | |
| CN116535484A (en) | Keratin BD-7, its preparation method, its pharmaceutical composition and use | |
| CN116036235A (en) | Application of transcription factor ETS2 in preparation of drugs for treating liver failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |