23 results about "Thrombopoiesis" patented technology

The invention relates to the field of biological medicine, and provides an application of a dihydroorotate dehydrogenase inhibitor in preparation of megakaryocytes, and the dihydroorotate dehydrogenase inhibitor is a compound shown as a formula I, a formula II or a formula III, or a pharmaceutically acceptable salt of the compound. According to the technical scheme, the dihydroorotate dehydrogenase inhibitor can promote hematopoietic stem / progenitor cells to differentiate into megakaryocytes and platelets, the platelet generation amount is increased by about 2 times, and a promising strategy is provided for in-vivo and in-vitro megakaryocyte and platelet generation.

The present disclosure relates to the field of biological medicine, and provides a use of a dihydroorotate dehydrogenase inhibitor in the preparation of megakaryocytes, wherein the dihydroorotate dehydrogenase inhibitor is a compound represented by formula I, formula II or formula III, or a pharmaceutically acceptable salt of the compound. The dihydroorotate dehydrogenase inhibitor in the technical solution of the present disclosure can promote the differentiation of hematopoietic stem / progenitor cells into megakaryocytes and platelets, and increase the platelet production by about 2 times, thereby providing a promising strategy for the production of megakaryocytes and platelets in vivo and in vitro.

Described are various embodiments of anti-cancer polypeptides, nucleic acid constructs. and methods of using same, particularly for the expression of protein comprising three thrombospondin-1 type 1 repeats (3TSR), as well as pharmaceutical compositions comprising any of the disclosed polypeptides or nucleic acid constructs for the treatment of solid tumor cancers such as ovarian cancer or pancreatic cancer.

A hematopoietic stem cell (HSC) proliferation medium includes a basal medium, 0.1 ng / mL to 200.0 ng / mL of thrombopoietin (TPO), 0.1 ng / mL to 200.0 ng / mL of stem cell factor (SCF), 0.1 ng / mL to 20.0 ng / mL of interleukin-3 (IL-3), 0.1 ng / mL to 100.0 ng / mL of interleukin-6 (IL-6), 0.1 ng / mL to 200.0 ng / mL of Flt-3 ligand (FL), 0.1 μg / mL to 20.0 μg / mL of insulin, 0.1 μg / mL to 120.0 μg / mL of transferrin, 0.1 g / L to 3.0 g / L of human serum albumin (HSA), 0.1 μM to 4.0 μM of pyrimido-indole derivative UM729, and 0.1 μM to 2.0 μM of aryl hydrocarbon receptor (AhR) antagonist StemRegenin 1 (SR1). Methods for in vitro proliferation of hematopoietic stem cells (HSCs) and in vitro production of hematopoietic progenitor cells (HPCs) using the HSC proliferation medium are also provided.

The invention discloses a freeze-dried preparation of a pegylated thrombopoietic peptide as well as a preparation method and application of the freeze-dried preparation. The freeze-dried preparation comprises the pegylated thrombopoietic peptide, histidine, glycine, mannitol and cane sugar. The preparation method of the pegylated thrombopoietic peptide comprises the following steps: carrying out coupling treatment on the thrombopoietic peptide and polyethylene glycol to obtain the pegylated thrombopoietic peptide, the thrombopoiesis promoting peptide is prepared from fusion protein; the amino acid sequence of the fusion protein is shown as Xm-(Y-Z) n, X is an insulin glargine mutant, Y is a restriction enzyme cutting site, Z is a thrombopoiesis promoting peptide, m is 1 or 2, and n is 1 or 2. The fusion protein is efficiently expressed in a thallus in the form of an inclusion body, the expressed fusion protein is cut by adopting specific protease, the thrombopoiesis promoting peptide is released, the integrity of the thrombopoiesis promoting peptide can be ensured, and the cutting efficiency is high. The pegylated thrombopoiesis promoting peptide and the preparation thereof can effectively treat and prevent tumor drug related thrombocytopenia, primary immune thrombocytopenia, chronic liver disease related thrombocytopenia and acute radiation syndrome hematopoietic syndrome.

Provided herein are polypeptides, compositions, and methods for treating a cancer in an individual using a polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain. Also provided herein are nucleic acids encoding such polypeptides, expression vectors and cells comprising such nucleic acids, and methods of producing the polypeptides comprising a thrombopoietin domain and a Flt3 ligand domain. The administration of a fusion polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain to a subject may treat and reduce the symptoms of hematopoietic failure, including thrombopenia, and / or acute radiation syndrome.

Provided is a novel recombinant human thrombopoietin composition. More specifically, provided is a composition, the composition comprising thrombopoietin (TPO), one or more protein protecting agents, a filler, a surfactant and a pH adjusting agent, and the composition being free of human serum albumin. Provided are a method for preparing a lyophilized powder for injection and a lyophilized powder for injection prepared by the method. The method comprises performing pre-freezing at about −50°C or below or about −45°C or below , performing primary drying at about −40°C to about 0°C, and performing secondary drying at about 0°C to about 30°C.

The invention provides application of a small molecule compound CD0035 in preparation of a medicine for treating thrombocytopenia, and relates to the technical field of pharmaceutical preparations. According to the application, through a large number of experimental exploration, the small molecule CD0035 has no influence on the cytotoxicity and cell viability of megakaryocytes in vitro, and has certain activity of promoting differentiation and maturation and prothrombopoiesis on the megakaryocytes in vitro; meanwhile, research finds that the CD0035 has a promoting effect on thrombocytopenia in vivo, can recover the platelet level of a mouse with the thrombocytopenia caused by irradiation, and promotes differentiation and maturation of megakaryocytes in bone marrow and spleen of main hematopoietic tissues and generation of polyploids, so that the small molecule compound CD0035 has a certain effect on treating the thrombocytopenia, and can be used for preparing medicines for treating the thrombocytopenia. And a theoretical basis is provided for treatment and development of thrombocytopenia.

The invention provides application of thrombopoietin in preparation of CAR-T (Chimeric Antigen Receptor-T) cells and a preparation method of the CAR-T cells. The preparation method of the CAR-T can effectively shorten the production cycle, is simple and convenient to operate, and has a wide industrial application prospect.

One aspect relates to: olsalkene; a preparation method therefor; a composition for preventing or treating thrombocytopenia, comprising same; and use thereof. According to one aspect, it has been identified that olsalkene is not cleaved by azoreductase (AzoR) and binds to biliverdin reductase (BLVRB) in the body, thereby inhibiting the reduction of biliverdin (BV) to bilirubin (BR). In addition, it has been identified that platelet production is promoted through the inhibition of biliverdin reductase B activity. Therefore, the olsalkene can be effectively used as a therapeutic agent for thrombocytopenia or as a health functional food through the role of promoting platelet production by inhibiting the activity of biliverdin reductase B.

The invention discloses a pharmaceutical composition for preventing and treating acute radiation sickness and application thereof. Animal experiments prove that the combined use of the estrogen anti-release drug and the thrombopoiesis promoting drug can obviously improve the survival rate of animals irradiated by lethal and even super lethal dose, can obviously increase the proportion and absolute quantity of hematopoietic stem cells and progenitor cells in bone marrow of the irradiated animals, and enhances the extramedullary hematopoietic activity of the spleen at the same time; and the recovery of hematopoietic functions of leukocytes, platelets and erythrocytes is promoted. According to the invention, the treatment effect on acute radiation sickness is remarkably improved by combining the estrogen drugs and the thrombopoiesis promoting drugs, and a new treatment scheme is provided for prevention and treatment of acute radiation sickness.

Provided are a lyophilized preparation of a PEGylated thrombopoietic peptide, a preparation method therefor and a use thereof. The lyophilized preparation comprises a PEGylated thrombopoietic peptide, histidine, glycine, mannitol, and sucrose; the preparation method for the PEGylated thrombopoietic peptide comprises: conjugating a thrombopoietic peptide with polyethylene glycol to obtain a PEGylated thrombopoietic peptide, wherein the thrombopoietic peptide is prepared by using a fusion protein, an amino acid sequence of the fusion protein is as shown in Xm-(Y-Z)n, X is an insulin glargine mutant, Y is a protease cleavage site, Z is the thrombopoietic peptide, m is 1 or 2, and n is 1 or 2. The described fusion protein is efficiently expressed in the form of inclusion bodies in bacteria. The expressed fusion protein is cleaved by means of a specific protease to release a thrombopoietic peptide, which ensures the integrity of the thrombopoietic peptide and high cleavage efficiency. The provided PEGylated thrombopoietic peptide and the preparation thereof can effectively treat and prevent cancer treatment-induced thrombocytopenia, primary immune thrombocytopenia, chronic liver disease-associated thrombocytopenia, and hematopoietic acute radiation syndrome.

The invention discloses a pharmaceutical composition for treating and curing acute radiation sickness, which comprises idebegrasbine alpha and a thrombopoiesis promoting drug (ropursbine or rhTPO), according to the application disclosed by the invention, for the first time, the fact that the combination of the idebesisterone alpha and the thrombopoiesis promoting drug (ropsisterone or rhTPO) has a remarkable synergistic effect on the treatment of the acute radiation sickness is found, and an effective drug combination strategy is provided for the treatment of the acute radiation sickness; the compound has a wide application prospect in the technical field of development of acute radiation sickness prevention and treatment medicines.

The invention discloses application of combination of dimethyl sulfoxide and thrombopoiesis promoting drugs in treatment of acute radiation sickness. It is found for the first time that a combined scheme of DMSO and thrombopoiesis promoting drugs can significantly improve the survival rate of animals irradiated by lethal and even super lethal dose, animal weight reduction caused by radiation is reversed, and a significant synergistic effect is shown. The invention provides a safe and reliable radiation prevention and treatment measure for patients suffering from acute high-dose radiation exposure, and has a wide clinical application scene.

The invention discloses an adeno-associated virus AAV vector. The adeno-associated virus AAV vector comprises a cytokine gene, the cell factor is selected from any one or more than two of the following components: human interleukin 2 (IL2), human interleukin 3 (IL3), human interleukin 6 (IL6), human interleukin 15 (IL15), human thrombopoietin (THPO), human stem cell factor (SCF) and human granulocyte-macrophage colony stimulating factor (GM-CSF). The invention also discloses an AAV vector combination comprising any two or more than three AAV vectors mentioned above. The invention also discloses an application of the AAV vector and a combination of the AAV vector in construction of immune system humanized non-human animals. The invention further discloses a method for constructing the immune system humanized non-human animal.

This invention relates to a novel recombinant human thrombopoietin composition. More specifically, this invention relates to a composition comprising thrombopoietin (TPO), one or more protein protectants, fillers, surfactants, and pH adjusters, and the composition is free of human serum albumin. This invention also relates to a method for preparing a lyophilized powder for injection and the lyophilized powder for injection prepared by this method, the method comprising pre-freezing at a temperature below about -50°C or about -45°C, a first drying at a temperature from about -40°C to about 0°C, and a second drying at a temperature from about 0°C to about 30°C.

The invention belongs to the technical field of biological genetic engineering, and particularly relates to a canine TPO recombinant protein, a mutant, a fusion protein and application thereof. A recombinant protein is obtained by screening a high-expression signal peptide and replacing a natural signal peptide in canine TPO, protein expression can be efficiently induced, mutant protein with higher expression quantity and biological activity is obtained by performing amino acid site mutation on a mature peptide cTPO in canine TPO, and the canine TPO recombinant protein and a mutant thereof are fused with truncated CTP, so that the canine TPO recombinant protein is obtained. The expression quantity and activity of the fusion protein are remarkably improved, an amino acid sequence of the fusion protein is subjected to codon optimization modification and then is expressed by using an efficient CHO expression system, and the problems that in the prior art, dog-derived thrombopoietin is short in half-life period and insufficient in stability, and heterologous protein has immunogenicity worry are solved. The canine TPO fusion protein can be effectively applied to preparation of drugs for treating canine primary or secondary thrombocytopenia.

Provided are a nucleic acid encoding thrombopoietin or a precursor thereof, and a composition and kit comprising same. Further provided is a use of the nucleic acid, the composition and the kit in treatment of thrombocytopenia.

Provided herein are methods, compounds, and compositions for safely reducing thrombopoietin in a cell or an individual. Such methods, compounds, and compositions maintain platelet count within a safe hemostatic range. Such methods, compounds, and compositions are useful to safely treat, prevent, or ameliorate a disease that can benefit from platelet count reduction in an individual. Such methods, compounds, and compositions are useful for treating or preventing diseases in which thrombopoietin contributes to the presence or activation of platelets contributes to and promotes disease initiation or progression, and / or adversely affects disease outcome.

A method for diagnosing a patient's breast cancer (BC) health state, or change in BC health state, or for diagnosing risk of BC or the presence of BC in a patient, comprises detecting, in a plasma sample from the patient, one or more biomarker values that correspond to thrombospondin- 1 (THBS1) or a THB SI -containing complex structure by performing a capillary electrophoresis under non-reducing conditions, and assigning the patient as having or not having BC, or having or not having a change in BC health state, or having or not having a risk of BC based on the biomarker values.

The invention provides application of adipose-derived stem cell artificial nano-vesicles in preparation of drugs for promoting platelet generation. The invention also provides an adipose-derived stem cell artificial nano-vesicle loaded with a sanguisorba monomer DMAG, and the adipose-derived stem cell artificial nano-vesicle is prepared by extracting a cell membrane of adipose-derived stem cells and entrapping DMAG by using a natural phospholipid bilayer structure of the cell membrane so as to form a nano-sized vesicle structure. The artificial nano-vesicle inherits good biocompatibility of adipose-derived stem cells, can effectively reduce immunological rejection of an organism, and protects DMAG from degradation effects such as in-vivo enzymolysis and the like; and a protective delivery system can be formed in vivo, so that rapid metabolism and elimination of DMAG in vivo are reduced, and the effective release time of DMAG in vivo is prolonged. The artificial nano-vesicles significantly increase the number of peripheral blood platelets, shorten the bleeding time and reduce the immunogenicity at the same time.

The present disclosure discloses a composition, method and application thereof for improving the quality of in vitro maturation of oocytes and the pregnancy rate after in vitro produced embryos transfer. The present disclosure aims at the problems of low maturation rate and poor subsequent embryo development potential caused by metabolic disorders during in vitro maturation of oocytes, and provides a composition including two or more regulators in vitamin C, L-carnitine and thrombopoietin to regulate the metabolism of oocytes, thereby greatly improving the in vitro maturation rate of oocytes and the subsequent embryo development potential. The present disclosure not only improves the efficiency of in vitro embryo production of livestock, but also provides a reference for improving the efficiency of human assisted reproductive technology. The method is simple, safe and efficient, and has great application value and broad application prospects.

Provided herein are methods, compounds, and compositions for safely reducing thrombopoietin in a cell or an individual. Such methods, compounds, and compositions maintain platelet count within a safe hemostatic range. Such methods, compounds, and compositions are useful to safely treat, prevent, or ameliorate a disease that can benefit from platelet count reduction in an individual. Such methods, compounds, and compositions are useful for treating or preventing diseases in which thrombopoietin contributes to the presence or activation of platelets contributes to and promotes disease initiation or progression, and / or adversely affects disease outcome.