78 results about "Fibroblast growth factor 23" patented technology

The present invention provides Fibroblast Growth Factor-23 (FGF-23) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing FGF-23 polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and / or prevention of diseases, disorders, and conditions associated with FGF-23 polypeptides.

The present invention relates to an isolated chimeric protein. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule. The present invention also relates to a pharmaceutical composition including an isolated chimeric protein and a pharmaceutically acceptable carrier. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule, and a pharmaceutically-acceptable carrier. Yet another aspect of the present invention relates to a method for treating a subject suffering from a disorder. This method includes selecting a subject suffering from the disorder and administering to the subject a therapeutically effective amount of a chimeric protein according to the present invention.

The present invention relates generally to methods of in vitro diagnostics, in particular the use of a compound selected from the group consisting of fibroblast growth factor 23 (FGF23), inorganic phosphorus (P), the product of inorganic phosphorus and total calcium (P×tCa), osteopontin (OPN) and parathyroid hormone (PTH) as biomarker. Said biomarkers can be used to monitor the modulation of fibroblast growth factor receptor (FGFR) kinase activity, in particular its inhibition, and / or the occurrence of secondary effects of FGFR inhibition. The invention further provides methods and kits relating to these uses.

The present invention relates to the identification of new proteins comprising fibroblast growth factor 21 (FGF21) and other metabolic regulators, including variants thereof, known to improve metabolic profiles in subjects to whom they are administered. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

The present invention relates to mutants of Fibroblast Growth Factor (FGF), particularly FGF-20 and FGF-21, which contain newly introduced N-linked or O-linked glycosylation site(s). The polynucleotide coding sequences for the mutants, expression cassettes comprising the coding sequences, cells expressing the mutants, and methods for producing the mutants are also disclosed. Further disclosed are pharmaceutical compositions comprising the mutants and method for using the mutants.

The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and / or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

The present invention relates to an isolated chimeric protein. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule. The present invention also relates to a pharmaceutical composition including an isolated chimeric protein and a pharmaceutically acceptable carrier. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule, and a pharmaceutically-acceptable carrier. Yet another aspect of the present invention relates to a method for treating a subject suffering from a disorder. This method includes selecting a subject suffering from the disorder and administering to the subject a therapeutically effective amount of a chimeric protein according to the present invention.

The present invention relates to the identification of new proteins comprising fibroblast growth factor 21 (FGF21) and other metabolic regulators, including variants thereof, known to improve metabolic profiles in subjects to whom they are administered. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

The invention discloses a mutant fibroblast growth factor (FGF-21) and use of the mutant fibroblast growth factor in treating endocrine diseases. The amino acid sequence of the fibroblast growth factor-21 disclosed by the invention is shown as SEQ ID NO: 2, and the sequence of a gene for encoding the mutant fibroblast growth factor is shown as SEQ ID NO: 1. According to the invention, a wild typeFGF-21 is used as a template, two arginine (Arg) residues are introduced through a downstream primer, and a mutant is obtained through polymerase chain reaction (PCR). The strong basicity and positive charges in the physiological condition of Arg are mainly utilized so that the isoelectric point of FGF-21 is up-regulated, and FGF-21 binding to the surfaces of cell membranes is facilitated. The results of an animal experiment show that the mutant FGF-21 disclosed by the invention can more effectively reduce the blood glucose level in an animal, and furthermore, the mutant disclosed by the invention has the advantages of fast onset of drug action, lasting drug effect and the like in reducing the blood glucose level. The mutant GF-21 disclosed by the invention can be used as a medicine to treat endocrine diseases such as diabetes, metabolic syndrome, lipid metabolism disorder and the like.

The invention discloses a recombinant protein of a human fibroblast growth factor 21 as well as a preparation method and application thereof. The preparation method comprises the following steps: linking a nucleotide sequence of a coding gene of the human fibroblast growth factor 21 recombinant protein with an expression vector to obtain a recombinant expression vector; transforming the recombinant expression vector into host cells, screening high-expression positive host cells, culturing the cells, inducing the cells to express the human fibroblast growth factor 21 recombinant protein, collecting thalli, breaking, and carrying out centrifuging, clarification and purification, so as to obtain the target product, namely the human fibroblast growth factor 21 recombinant protein. The invention further discloses application of the human fibroblast growth factor 21 recombinant protein in the preparation of drugs for treating metabolic diseases. Compared with a wild hFGF21 protein, the human fibroblast growth factor 21 recombinant protein (mFGF21) has the advantages that the activity is remarkably improved, and the blood glucose level in a diabetic mouse can be relatively effectively reduced.

The invention discloses a preparation method of chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors. The preparation method of chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors is characterized by taking chitosan quaternary ammonium salt and sodium hyaluronate as raw materials and synthesizing a target product through a two-step process of ionic cross-linking and polymer condensation. The preparation method comprises the following steps: firstly mixing a chitosan quaternary ammonium salt solution with a basic fibroblast growth factor solution, and then dropwise adding a sodium tripolyphosphate solution into the mixed solution to prepare an ionic cross-linked mixed solution; and finally dropping sodium hyaluronate into the ionic cross-linked mixed solution for carrying out polymer condensation to prepare chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors. The average particle diameter of the nanogel is 150-230nm; the Zeta potential is -28.6 to -36.7mV. The nanogel can be used for treating dental ulcer and has good research, development and utilization prospects.

The invention discloses a basic fibroblast growth factor composition, which comprises the following components by mass percentage: 0.01-0.05% of a basic fibroblast growth factor, 1.2-3% of mannitol, 0.05-0.2% of hyaluronic acid, 0.01-0.2% of tea polyphenol and the balance of first purifying water. The invention also provides a preparation method of the basic fibroblast growth factor composition. The invention also provides a hair regenerator, and two preparation methods of the hair regenerator. The invention also provides an application method of the hair regenerator. The basic fibroblast growth factor in the composition can stimulate and promote the differentiation of hair follicle stem cells, prevents the hair follicle cell atrophia-degeneration, has restoration function of the hair follicle cells with atrophia-degeneration, gradually improves the microenvironment of hair root growth, and promotes the full nutrition supply for the root of hair and normal growth of the hair root.

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

A discovery process beginning with an in vivo screening of proteins, peptides, natural products, classical medicinal compound or other substances. The administration of compounds to the animal can be either direct or indirect, such as by the administration and expression of cDNA-containing plasmids. Since the discovery process of the invention is based on a non-preconceived hypothesis and whole organism multi-organ analysis, a compound can be selected for testing in the absence of any biological selection criteria. The resulting organism-wide pattern of the gene expression changes in the transcriptome provides an overview of the activities at the molecular and organism-wide levels. The discovery process of the invention then integrates in vivo profiling and internal and external genomic databases to elucidate the function of unknown proteins, typically within few months. The invention further relates to medical uses of fibroblast growth factor 23 (FGF-23), FGF-23 fragments, FGF-23 C-terminal polypeptides, FGF-23 homologs and / or FGF-23 variants.

The invention discloses a human stem cell factor skin repairing solution and a preparation method thereof. The solution is prepared from the following components by content: 50-75ug / l of epidermal growth factor, 15-20ug / l of acidic fibroblast growth factor, 15-20ug / l of basic fibroblast growth factor and 4-6ug / l of vascular endothelial growth factor. A series of cell factors against quick proliferation of germinal cells, and the effects of quickly repairing damaged skin and repairing skin quality can be achieved according to reasonable environment which accords with human cell growth and accelerating growth.

The invention discloses gel for promoting wound healing and repairing cervical mucosa. The gel is prepared from the following components in percentage by mass: 1 to 3 percent of carbomer, 0.1 to 0.5 percent of triclosan, 0.05 to 0.1 percent of hyaluronic acid, 0.000001 to 0.00005 percent of a basic fibroblast growth factor, 0.000001 to 0.00005 percent of a transforming growth factor beta, 0.05 to 0.1 percent of sodium hydroxide and the balance of pure water. According to the product, wound healing can be promoted; the product also has efficient antibacterial and bactericidal performance, is biologically safe and nontoxic and stable in performance, has treatment effects on gynecological diseases such as vaginitis (bacterial vaginosis, monilial vaginitis, mixed vaginitis and vulvitis) and cervical erosion, and also has the effects of cleaning and caring the private parts of females, stopping bleeding, relieving pain, diminishing inflammations, resisting bacteria and promoting wound healing.

Immunoassays, assay methods, antibodies and methods of producing antibodies for the detection of fibroblast growth factor-23 (FGF-23). The immunoassay and assay method preferably comprise a non-competitive, sandwich-type assay utilizing a first bound antibody having affinity to a first site of the FGF-23 molecule, and a second, labeled antibody having an affinity for a second site present upon the FGF-23 molecule. The antibodies and methods of generating the same include administering antigenic peptide fragments of the FGF-23 molecule, monitoring the antibody titre produced thereby, extracting and selecting antibodies from the antisera having a specificity for the desired antigenic region of FGF-23, and purifying same. The antibodies may be incorporated into the immunoassay of the present invention or utilized for a variety of assay-type purposes for the detection of FGF-23.

The purpose of the present invention is to provide an antibody against fibroblast growth factor 23. The antibody is obtained by immunizing an animal with a polypeptide which comprises an amino acid sequence represented by SEQ ID NO: 1, or an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO: 1 by deletion, substitution, or addition of 1 or several amino acids, and has fibroblast growth factor-23 activity and activity to control phosphate metabolism or vitamin D metabolism, and is shown by the following (a), (b), or (c): (a) an antibody, which recognizes an amino acid sequence between the 180 and the 194, or the 237 and the 251<st> amino acid residues represented by SEQ ID NO: 1; (b) an antibody, which is produced by a hybridoma whose accession number is FERM BP-7838, FERM BP-7839, FERM BP-7840, or FERM BP-8268; or (c) an antibody, which is competitive with the antibody produced by the hybridoma whose accession number is FERM BP-7838, FERM BP-7839, FERM BP-7840, or FERM BP-8268 upon binding with the polypeptide comprising the amino acid sequence represented by SEQ ID NO: 1. <IMAGE>

The invention relates to a production method for recombinant human fibroblast growth factor-18 protein. The production method comprises the following steps: 1, expressing the fibroblast growth factor-18 protein in insect cells by using an insect baculovirus vector expression system, specifically comprising 1) obtaining recombinant baculovirus Bacmid-FGF18 (fibroblast growth factor-18), wherein the FGF18 gene is a fibroblast growth factor-18 gene and has a base sequence as shown in SEQ ID NO: 1, and 2) infecting the insect cells with the Bacmid-FGF18 recombinant baculovirus with MOI (Multiplicity of Infection) of 1 to 32, and then culturing the infected insect cells for 12 to 96 hours at the temperature of 25 to 29 DEG C to harvest cell fluid; and 2, purifying the cell fluid harvested in the step 1 to obtain the human fibroblast growth factor-18 protein. The invention also discloses application of the human fibroblast growth factor-18 protein in treating bone diseases and alopecia.

The invention discloses application of FGF (fibroblast growth factor) 9 in preparation of osteoarthritis cartilage repair promotion medicines, researches find the FGF9 can play the role of retardation of abnormal differentiation of articular cartilage cells in the articular cartilage cells in the inflammatory environment, the FGF9 can alleviate the articular cartilage degradation in an osteoarthritis model in mice, can inhibit key enzyme MMP-13 of articular cartilage degradation, can slow down the hypertrophy process of articular cartilage, can be use for preparation of the osteoarthritis cartilage repair promotion medicines, and has good potential application prospect in the osteoarthritis treating field.

The present invention relates to the use of a plasmid encoding a fibroblast growth factor as therapeutic agent for the prevention and treatment of hypercholesterolemia or diabetes associated myocardial or skeletal angiogenic defects. The present invention also relates to a method for enhancing formation of both collateral blood vessels and arterioles in myocardial or skeletal ischemic tissues in a mammalian subject suffering from hypercholesterolemia or diabetes. The present invention further relates to a method of promoting collateral blood vessels in ischemic myocardial or skeletal tissues without inducing VEGF-A factor expression and causing edema in the treated muscles.

The invention relates to a culture medium and a method for inducing human amniotic epithelial stem cells to be differentiated into melanocytes. Endothelin 3, dexamethasone, stem cell factors, basic fibroblast growth factors, insulin-iron-selenium transducin and fetal bovine serum are added into an alpha-MEM basic culture medium. The method comprises the following steps: preparing human amniotic membranes into a human amniotic epithelial stem cell suspension solution; adding cells into the alpha-MEM basic culture medium added with the endothelin 3, the dexamethasone, the stem cell factors, thebasic fibroblast growth factors, the insulin-iron-selenium transducin and the fetal bovine serum; culturing in an incubator with the temperature of 37 DEG C and 5 percent of CO2 to obtain an amnioticepithelial stem cell adherent single layer; gradually inducing to be differentiated into the melanocytes of melanocyte marker gene tyrosinase-associated proteins 1 (trp 1) and 2 (trp 2), a microphthalmia-associated transcription factor (mitf) and positive tyrosinase (dtc). The culture medium and the method, provided by the invention, have the characteristics of abundant cell sources, low immunogenicity, no ethical limitation and simple induction method.

The present invention provides a collagen sustained release hydrogel containing human fibroblast growth factor 10, the collagen sustained release hydrogel comprises the human fibroblast growth factor10 (FGF10P) and excipients, wherein the excipients include collagen, poloxamer 407, glycerol and trehalose.

The invention discloses an acne-removing mark-removing transparent emulsion containing a basic fibroblast growth factor and a preparation method thereof. The emulsion comprises following components: the basic fibroblast growth factor, tea tree essential oil, azelaic acid, vitamin, an emollient, a humectant, a surfactant, a phosphoric acid buffer and deionized water. The basic fibroblast growth factor in the emulsion is capable of effectively renewing growth of subcutaneous connective tissue, improving microcirculation and removing acne marks. The tea tree essential oil and the azelaic acid both have bacteriostatic and antiphlogistic functions, and synergistic effects can effectively diminish inflammation and remove acne. The emulsion is good in moistening property and is free of irritation to skin.

The present invention relates to a method for assessing whether a subject shall be subjected to an imaging based diagnostic assessment. The method is based on the determination of the amount(s) of a cardiac Troponin and / or Fibroblast Growth Factor 23 (FGF-23) in a sample from the subject, and on the comparison of the, thus, determined amount(s) with a reference amount (reference amounts). The present invention also relates to a system for performing an assessment whether a subject shall be subjected to an imaging based diagnostic assessment and to reagents and kits used in performing the methods disclosed herein. Moreover, the present invention is directed to a method for predicting the risk of mortality and / or of a cardiovascular event. Also encompassed is a method for diagnosing an early stage of LVH in a subject having a preserved left ventricular ejection.

The invention discloses a human umbilical cord mesenchymal stem cell culture solution. The culture solution comprises a concentrated lysate, an Iscove's modified medium and an insulin transferrin selenite supplement liquid according to a volume ratio of (4-6):100:(0.8-1.2), and also comprises 4-6 ng / mL of a trypsin inhibitor, 12-18 ng / mL of a recombinant human epidermal growth factor and 12-18 ng / mL of a basic fibroblast growth factor. The culture solution is adopted to carry out adherent culture on umbilical cord tissues; a TrypLE digestion juice is adopted to carry out digestion; and subculturing is carried out. Human umbilical cord mesenchymal stem cells obtained in the invention have high purity, and can be directly used in clinic researches; and a culture method has a high amplification efficiency, is convenient for material drawing, and avoids moral dispute. A culture system of the human umbilical cord mesenchymal stem cells contains no human serum or animal-derived protein components, greatly reduces adverse effects caused by introduction of exogenous proteins in clinic treatment, and can be directly applied to the clinic researches.

The invention discloses a biological agent for repairing skin injury and a preparation method of the biological agent, and belongs to the technical field of biology. The biological agent for repairingthe skin injury is prepared from, by weight, 8-12 g of adipose-derived stem cell active matter, 4-6 g of amnion, 0.05-0.1 g of epidermal growth factors, 0.05-0.1 g of fibroblast growth factors, 4-8 gof fibroblasts, 0.005-0.01 g of fibronectin and 40-60 ml of deionized water. The biological agent for repairing the skin injury has the advantages that the injured skin can be repaired, and the healing efficiency of the skin is improved.

The invention belongs to the technical field of medicine, and specifically relates to applications of basic fibroblast growth factor (bFGF) in preparation of drugs for treatment of spinal cord injuries, wherein the spinal cord injuries comprise spinal cord primary injuries and spinal cord secondary injuries caused by various factors. According to the applications of the bFGF in preparation of the drugs for treatment of spinal cord injuries, the form of the drugs can comprise a powder injection, a water agent, a liposome, and the like. With the bFGF, endoplasmic reticulum stress can be inhibited, and spinal cord neuron apoptosis caused by endoplasmic reticulum can be reduced so as to provide a treatment effect for spinal cord injuries.

The present invention discloses fibroblast growth factor liposome lyophilized powder for preventing and treating alopecia, wherein the raw material components comprise fibroblast growth factor, silk fibroin, phospholipid, cholesterol and a transdermal absorption accelerator. According to the present invention, by adding the transdermal absorption accelerator into the liposome lyophilized powder, the transdermal absorption of the fibroblast growth factor is effectively improved so as to increase the drug distribution in the hair follicles, such that the fibroblast growth factor liposome lyophilized powder can be used for preventing and treating alopecia; and the preparation can be directly dispersed by physiological saline and then is sprayed at the scalp, can further be added to the gel matrix to prepare the lipid gel for being coated on the scalp, and has the alopecia prevention and treatment effect.