101 results about "Nephrotoxicity" patented technology

A method and kit for detecting the immediate or early onset of renal disease and injury, including renal tubular cell injury, utilizing NGAL as an immediate or early on-set biomarker in a sample of blood serum. NGAL is a small secreted polypeptide that is protease resistant and consequently readily detected in the blood serum following renal tubule cell injury. NGAL protein expression is detected predominantly in proximal tubule cells, in a punctuate cytoplasmic distribution reminiscent of a secreted protein. The appearance NGAL in the serum is related to the dose and duration of renal ischemia and nephrotoxemia, and is diagnostic of renal tubule cell injury and renal failure. NGAL detection is also a useful marker for monitoring the nephrotoxic side effects of drugs or other therapeutic agents.

An early-onset method and kit for detecting renal tubular cell injury, using NGAL as an early urinary biomarker. NGAL is a small secreted polypeptide that is protease resistant and thus readily detected in urine following tubular cell injury. NGAL protein expression was mainly detected in the proximal tubule cells, which resembled a secreted protein with a punctate distribution in the cytoplasm. Apparent NGAL in urine correlates with the amount and duration of renal ischemia and nephrotoxicemia and is a diagnostic feature of tubular cell injury and renal failure. NGAL detection is also a useful marker for monitoring nephrotoxic side effects of drugs or other therapeutic agents.

A method and kit for detecting the early onset of renal tubular cell injury, utilizing NGAL as an early urinary biomarker. NGAL is a small secreted polypeptide that is protease resistant and consequently readily detected in the urine following renal tubule cell injury. NGAL protein expression is detected predominantly in proximal tubule cells, in a punctate cytoplasmic distribution reminiscent of a secreted protein. The appearance NGAL in the urine is related to the dose and duration of renal ischemia and nephrotoxemia, and is diagnostic of renal tubule cell injury and renal failure. NGAL detection is also a useful marker for monitoring the nephrotoxic side effects of drugs or other therapeutic agents.

The disclosure relates to methods of ameliorating nephrotoxic side effects of immunosuppressive agents whose immunosuppressive activity is mediated via upregulation of TGF-β such as, for example, cyclosporine (CsA). The disclosure provides treatment modalities for use in patients that require immunosuppression, e.g., patients at risk of transplant rejection or having an autoimmune disease. In the methods of the invention, a TGF-β antagonist, e.g., an anti-TGF-β antibody, is administered to a patient treated with an immunosuppressive agent. Such a TGF-β antagonist is administered in a therapeutically effective amount sufficient to alleviate the nephrotoxic effects of the immunosuppressive agent without substantially interfering with immunosuppressive activity of the agent.

Use of cilastatin to reduce the nephrotoxicity of different compounds. The invention refers to use of cilastatin to prepare a medicinal product to reduce the nephrotoxicity of a nephrotoxic compound that enters the cells of the proximal tubule through cholesterol rafts. The invention is based on the discovery that a great number of nephrotoxic compounds, including drugs, enter the cells of the proximal tubule through the cholesterol rafts, and that cilastatin is able to interfere with this transport mechanism, decreasing the nephrotoxicity of such compounds to a variable extent. The nephroprotective effect is common to compounds of different chemical nature and solubility and is specific for the kidney, causing no interference with the effects of nephrotoxic drugs having their targets in other organs. Therefore, administration of cilastatin allows for decreasing the nephrotoxic effects of different drugs without reducing their therapeutic effects.

A conjugate compound comprising an acyclic nucleoside phosphonate covalently coupled to a lipid for the therapeutic and / or prophylactic treatment of viral infection in an immunodeficient subject is described, along with compositions and methods of using the same. A preferred conugate compound is CMX001, having formula (I) or a pharmaceutically acceptable salt thereof.

The invention provides compositions containing omega-3 oil and at least one anti-inflammatory agent and / or at least one gastrotoxic, nephrotoxic, or hepatotoxic pharmaceutical agent. The invention further provides kits containing these compositions and methods for decreasing pain or inflammation, decreasing the symptoms of an allergic condition, and / or the gastrotoxicity, nephrotoxicity, and hepatotoxicity of a pharmaceutical agent in a subject (e.g., a human) or companion animal requiring the administration of at least one composition containing omega-3 oil. The invention also provides methods for formulating an anti-inflammatory agent to increase its absorption rate requiring the mixing of omega-3 oil with the anti-inflammatory agent and methods of concentrating an omega-3 oil.

The present invention relates to new uses of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate, (amifostine) and other aminothiol compounds to treat and reverse toxicities caused by therapeutic agents, radiation treatment or diabetes. In particular, the invention provides a method for treating neurotoxicity and nephrotoxicity associated with the administration of chemotherapeutic agents.

The present invention relates to medical use of liposomes, more particular the first medical use of sPLA2 hydrolysable liposomes. Such liposomes may be used for targeted delivery of therapeutic agents to cancerous tissue and in such embodiments; the therapeutic agents are typically small molecule antitumor agents. Other aspects of the inventions relates to methods of reducing the side effects of therapeutic agents, e.g. reducing nephrotoxicity, neurotoxicity and gastrointestinal toxicity of a therapeutic agent. Yet another aspect of the present invention relate to methods of prolonging the therapeutic effect of a therapeutic agent.

The invention relates to application of a compound with a flavone skeleton structure as a Parkinsonism treating medicine. The compound with a flavone skeleton structure is an inhibitor for the catechol methylation transferase; and the compound specifically comprises radix scutellariae, scutellarein and structure derivatives of radix scutellariae and scutellarein, and can be used as a synergist of the Parkinsonism treating medicine levodopa. In-vitro activity test indicates that IC50 of the compound in inhibiting catechol methylation transferase can reach nanomole level, wherein the COMT(Catechol O Methyl Transferase) inhibition activity of scutellarein and the derivatives of scutellarein is superior to that of medicine tolcapone on the market. The rat overall pharmacokinetic study shows that by the joint application of scutellarein and levodopa, the blood concentration of levodopa can be obviously increased. Moreover, the compound does not generate active intermediate through metabolism activation or form toxic adduct together with biological macromolecules, thus the hepatotoxicity and nephrotoxicity caused by metabolism activation are avoided, and the compound has good prospect of patent medicine.

The present invention provides novel in vitro assays for determining the nephrotoxicity of a compound. These assays correlate well with in vivo nephrotoxicity and also provide high-throughput methods to screen multiple compounds for in vivo nephrotoxicity. In addition, the methods of the present invention may be adapted to screen for nephroprotectant compounds, including those that protect cells and animals from the nephrotoxic effects of aminoglycoside antibiotics.

A protein capable of transporting organic anions having amino acid sequences represented by SEQ ID NO: 1 or 2 or amino acid sequences derived therefrom by deletion, substitution or addition of one or more amino acid residues; and a gene coding for the protein. The protein and gene therefore are useful in vitro analysis of drug release and drug—drug interactions and development of method for screening drugs useful for preventing nephrotoxicity.

A conjugate compound comprising an acyclic nucleoside phosphonate covalently coupled to a lipid for the therapeutic and / or prophylactic treatment of viral infection in an immunodeficient subject is described, along with compositions and methods of using the same. A preferred conjugate compound is CMX001, having formula (I) or a pharmaceutically acceptable salt thereof.

Use of cilastatin to reduce the nephrotoxicity of different compounds. The invention refers to use of cilastatin to prepare a medicinal product to reduce the nephrotoxicity of a nephrotoxic compound that enters the cells of the proximal tubule through cholesterol rafts. The invention is based on the discovery that a great number of nephrotoxic compounds, including drugs, enter the cells of the proximal tubule through the cholesterol rafts, and that cilastatin is able to interfere with this transport mechanism, decreasing the nephrotoxicity of such compounds to a variable extent. The nephroprotective effect is common to compounds of different chemical nature and solubility and is specific for the kidney, causing no interference with the effects of nephrotoxic drugs having their targets in other organs. Therefore, administration of cilastatin allows for decreasing the nephrotoxic effects of different drugs without reducing their therapeutic effects.

The present invention relates to a polymyxin derivative wherein R1, R2 and R3 are optional and R1, R2, R3, R5, R8 and R9 are cationic or neutral amino acid residues selected so that the total number of positive charges at physiological pH is at least two but no more than three; and to a combination product comprising at least two such derivatives. The invention further relates to a method for treating, alleviating or ameliorating an infection in a subject, caused by a Gram-negative bacterium by administering a therapeutically effective amount of a derivative according to the present invention to said subject; to a method for sensitizing Gram-negative bacteria to an antibacterial agent by administering, simultaneously or sequentially in any order a therapeutically effective amount of said antibacterial agent and a derivative according to the present invention to said subject; to methods for developing novel antibiotics; for reducing the nephrotoxicity, for improving the pharmacokinetic properties of natural polymyxins and octapeptins; and for sensitizing clinically important bacteria to a host defence mechanism complement present in serum. Finally, the invention relates to a process for preparing such polymyxin derivatives.

Disclosed are a suppressant of toxicity such as hepatotoxicity and nephrotoxicity, induced by cancer chemotherapeutic agent, and a composition of cancer chemotherapeutic agent containing the suppressant. The suppressant of toxicity induced by a cancer chemotherapeutic agent contains xanthorrhizol as an active ingredient. Xanthorrhizol shows an excellent ability in suppressing ill effects generated by dosage of cancer chemotherapeutic agent, such as hepatotoxicity and nephrotoxicity.

The invention relates to a new pharmaceutical composition, a method of treatment of infection and also a process to prepare the composition. The infectious complications are important causes of morbidity and mortality. Hospital acquired pneumonia (HAP) remains the most severe nosocomial infection in intensive care units. Beta-lactams alone are always considered inadequate when P. aeruginosa and / or methicillin-resistant S. aureus are implicated as pathogens or copathognes. The present invention provides the desired empirical therapy for control of all bacterial infections. The invention provides antibiotic combination products for delivering at least two different antibiotics, through parenteral dosage form comprising protein-synthesis-inhibiting antibiotic which is amikacin or its sulphate salt and non-protein-synthesis-inhibiting antibiotic which is cefepime or its hydrochloride salt. The invention provides a total solution, against multiresistant P. aeruginosa, or Acinetobacter spp. and / or methicillin-resistant S. aureus, and are useful for intramuscular or intravenous administration as antibiotics for hospitalized patients with acute or serious infections. The pharmaceutical compositions described here normally have the least nephrotoxicity and have better efficacy and safety of cefepime plus amikacin combination.

The invention discloses a method for screening DOX (doxorubicin)-nephrotoxicity-resistant active substances through three-color fluorescence labeling. The method comprises the following steps: kidney cells are taken and added into to-be-screened substances for pre-protection; DOX is added for damage after the pre-protection is finished; a cell membrane integrity fluorescent probe, a mitochondrial membrane potential fluorescent probe and a cell nucleus fluorescent probe which have different excitation and emission wavelengths are added simultaneously into the damaged kidney cells for fluorescence labeling; fluorescence images of the cells are collected and analyzed after dying is finished, and the protection rates of the to-be-screened substances for cell membranes, mitochondria and cell nucleuses are calculated; and the active substances whose protection rates for the cell membranes, mitochondria and cell nucleuses are all higher than 15% are screened out from the to-be-screened substances. Three fluorescent probes are adopted to label the kidney cells simultaneously, the protection effects of the to-be-screened substances for the kidney cells are surveyed from different action mechanisms, the screening method has the characteristics of fastness, economy, high throughput and high content, and the screening result is more comprehensive and precise.

The present invention provides compositions and methods to reduce renal damage caused by nephrotoxic drugs. The invention provides compositions comprising an anionically substituted oligosaccharide, a nephrotoxic drug and a pharmaceutically acceptable carrier, where the oligosaccharide is present in an amount effective for substantially inhibiting the nephrotoxic effect of the drug.

A method of determining nephrotoxicity of pharmaceuticals by conducting a metabolite formation study in cells using PAH in a control group; measuring metabolite formation; exposing cells to pharmaceuticals in the treatment group; conducting the metabolite formation study using PAH; measuring the metabolite formation in the treatment group; comparing the metabolite formation in the control and treatment group, and making a determination as to the nephrotoxicity of pharmaceutical.

The invention relates to a method for determining the presence of renal damage in an individual and also to a method for detecting one or several proteins selected from the list comprising Reg3B, fetuin B, Ras-related GTP-binding protein A serine protease inhibitor A3L, subunit 1 of COP9, gamma subunit of ATP synthase, gelsolin, ribonuclease UK114, aminoacylase 1A, alpha-enolase, keratin 5, parvalbumin alpha, ribonuclease 4 or serine protease inhibitor A3K. The renal damage may be acute renal failure. Said renal pathologies may be caused by the administration of a nephrotoxic agent, wherein the nephrotoxic agent may be an aminoglycoside antibiotic such as gentamicin, or cisplatin. The invention also provides means to differentiate the renal damage or renal failure induced by gentamicin from that induced by cisplatin, through the biochemical analysis of the urinary level of Reg3B and / or gelsolin, or fragments thereof.

The present invention relates to a polymixin derivative, wherein R1, R2 and R3 are optional, but unessential, and R1, R2, R3, R5, R8 and R9 represent cationic or neutral amino acid residues specified so that total positive charge at physiological pH value makes at least two, but no more than three. The invention also refers to a method of treating, relieving or suppressing an infection in an individual caused by a gram-negative bacterium, by introducing a therapeutically effective amount of the derivative according to the present invention to the specified individual; to a method of sensitising the gram-negative bacteria to an antibacterial agent by introducing simultaneously or sequentially in any order the therapeutically effective amount of the specified antibacterial agent and the derivative according to the present invention to the specified individual. The invention also relates to a method for developing new antibiotics; reducing nephrotoxicity, improving pharmacokinetic properties of natural polymixins and octapeptines; and sensitising the clinically significant bacteria to the protective mechanism of a host complement found in serum, and also developing a method of producing such polymixin derivatives.

The present invention relates to a method for diagnosing contrast medium-induced nephrotoxicty in a subject based on comparing the amount of urotensin II and / or adiponectin in a sample of the subject obtained after administration of the contrast medium to the amount of urotensin II and / or adiponectin in a sample of the subject prior to administration of the contrast medium. Further encompassed by the present invention are a kit and a device for carrying out the method of the present invention.

Use of Fructus schisandrae in preparation of medicaments for preventing and reducing toxicity and side effects of antineoplastic agents. The toxicity and side effects of antineoplastic agents are cardiovascular toxicity, hepatotoxicity, nephrotoxicity, suppression of bone marrow, immunosuppression, or alopecia etc induced by antineoplastic agents. Fructus schisandrae and extracts thereof, especially ethanol extracts, schisandrin B, are effective in reducing antineoplastic agent's toxicity and side effects.

The present invention provides compositions and methods to reduce renal damage caused by nephrotoxic drugs. The invention provides compositions comprising a substituted cyclodextrin, a nephrotoxic drug and a pharmaceutically acceptable carrier, where the cyclodextrin is present in an amount effective for substantially inhibiting the nephrotoxic effect of the drug.

The disclosure relates to methods of ameliorating nephrotoxic side effects of immunosuppressive agents whose immunosuppressive activity is mediated via upregulation of TGF-β such as, for example, cyclosporine (CsA). The disclosure provides treatment modalities for use in patients that require immunosuppression, e.g., patients at risk of transplant rejection or having an autoimmune disease. In the methods of the invention, a TGF-β antagonist, e.g., an anti-TGF-β antibody, is administered to a patient treated with an immunosuppressive agent. Such a TGF-β antagonist is administered in a therapeutically effective amount sufficient to alleviate the nephrotoxic effects of the immunosuppressive agent without substantially interfering with immunosuppressive activity of the agent.

The present invention relates to the use of a compound for the preparation of a medicament for the prevention and / or treatment of induced cytotoxicity, such as nephrotoxicity and ototoxicity, in particular said cytotoxicity is induced as a result of drug treatment. In a preferred embodiment, the compound has at least two nitrogen atoms, more preferably at least two amino groups. The compound of the present invention can block the binding of cytotoxic compounds to megalin receptors, thereby inhibiting the uptake of the cytotoxic compounds into cells. The present invention also relates to novel compounds for use in said treatment, as well as methods of reducing the cytotoxicity of cytotoxic compounds, more particularly gentamicin.

The present invention provides a lipid membrane that contains a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, or 22. Use of the present invention enables screening for a chemical which regulates excretion of a chemical and / or a waste. Furthermore, use of the present invention enables an arbitrary chemical to be tested for nephrotoxicity and / or hepatotoxicity.