104results about How to "Prolonged plasma half-life" patented technology

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

To address the issue of degradation by enzymatic reactions to proteins and peptides, polyethylene glycol (PEGylation) of the proteins and peptides has been established. PEGylated proteins and peptides have increased plasma half-lives and reduced immunogenicity. To further improve and extend the plasma half-life of desired protein or peptide therapeutics, a novel branched molecule of PEG possessing three PEGs with a single point of attachment is designed in this invention disclosure.

The invention discloses a fusion protein of a novel coronavirus envelope protein and an application of the fusion protein. The fusion protein (SARS2-RBD-Fc) is obtained by fusing an RBD structural domain of a novel coronavirus envelope protein S with an antibody Fc fragment; and as a subunit vaccine, the fusion protein can induce an organism to generate an efficient neutralizing antibody through nasal drip immunization and intramuscular injection. It indicates that the SARS2-RBD-Fc can be used as a candidate vaccine for preventing and treating new coronavirus infection.

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Thrombolytic therapy in the treatment of a cardiovascular event such as myocardial infarction (MI) carries with it a chance of suffering a hemorrhagic incident leading to severe disability and often death. Methods for the evaluation of proper therapy for a specific patient who has suffered a cardiovascular event employ a variety of bio-markers including cellular fibronectin (c-Fn) assembled as a panel for evaluation. Methods are disclosed for selecting markers and correlating their combined levels with a clinical outcome of interest. In various aspects the methods permit early detection of potential bleeding events, determination of the prognosis of a patient presenting cardiovascular damage, and identification of a patient at risk for hemorrhage when given thrombolytic therapy. The disclosed methods provide rapid, sensitive and specific assays to greatly reduce the risk of bleeding or the number of patients that can receive the most beneficial treatment for their cardiovascular event, and to reduce the human and economic costs associated with bleeding following such treatments.

The present invention relates to antidotes of anticoagulants targeting factor Xa which antidotes are used in combination with blood coagulating agents or other heparin antidotes to prevent or reduce bleeding in a subject. The antidotes described herein have reduced or no intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is or will be undergoing anticoagulant therapy with a factor Xa inhibitor.

The present invention relates to antidotes of anticoagulants targeting factor Xa which antidotes are used in combination with blood coagulating agents or other heparin antidotes to prevent or reduce bleeding in a subject. The antidotes described herein have reduced or no intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is or will be undergoing anticoagulant therapy with a factor Xa inhibitor.

A nucleic acid delivery complex is provided which comprises a condensed polypeptide / nucleic acid complex and a cationic lipid wherein the complex comprises (a) a nucleic acid sequence of interest (NOI); and (b) one or more viral nucleic acid packaging polypeptides, or derivatives thereof, said polypeptides or derivatives thereof being (i) capable of binding to the NOI; and (ii) capable of condensing the NOI; and wherein the NOI is heterologous to the polypeptide. Also provided is a method of introducing an NOI into a cell using the delivery vector.

The invention discloses a method for preparing enoxaparin sodium, comprising the steps of salinizing, drying, esterfying, alcohol precipitating, oxidizing, alcohol precipitating, fine filtering and freeze drying. In the method provided by the invention, a hydrophilic liquid phase reaction, a hydrophobic liquid phase reaction and a solid phase reaction are adopted, so that macromolecule sodium heparin is degraded into micromolecule sodium heparin with a specific structure, and the molecular weights of products and molecular weight distribution ranges are controlled, thus anti-FIIa activity resulting in bleeding risk is greatly reduced, the anti-FXa activity is relatively improved, and the product effectiveness and safety advantages are obvious. The enoxaparin sodium can be used for effectively preventing venous thromboembolism and pulmonary embolism, can be used for thrombosis before and after operations of orthopedic surgery and neurosurgery, and can be used for greatly reducing apoplexy risk, more effectively reducing death, cardiac failure and recurrent angina of patients suffering from unstable coronary artery syndromes, reducing hypertriglyceridemia and effectively eliminating the side effects of haemorrhage, osteoporosis and induced thrombocytopenia after long-term use of common unfractionated heparin sodium and derivates of common unfractionated heparin sodium.

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

The invention relates to long-acting glucagon-like peptide 1 (GLP-1) analogues and a synthesis method thereof. GLP-1 analogues with longer pharmacological action time are obtained through adding a modified 37th amino acid to natural GLP-1, the synthesis of target polypeptides is quickly realized through a microwave-promoted solid-phase synthesis method, and crude products are purified and freeze-dried to obtain the GLP-1 analogues.

Cytokine derivatives capable of homing the tumoral vessels and the antigen presenting cells and the use thereof as antitumoral agents.

The invention relates to the use of a Factor VIIa for the manufacture of a medicament for treatment of a condition affectable by Factor VIIa, said medicament being for subcutaneous, intramuscular or intradermal administration, and to the use of a Factor VIIa for the manufacture of a medicament for treatment of a condition affectable by Factor VIIa, wherein said medicament, when administered subcutaneously, intradermally or intramuscularly, shows a prolonged biological half-life.

The invention relates to a long-acting Exendin-4 analogue and a synthesis method thereof. Exendin-4 is transformed to obtain the Exendin-4 analogue having longer pharmacological action time, synthesis of a target polypeptide is rapidly achieved by a microwave-promoted solid phase synthesis method, and a crude product is purified and freeze-dried to obtain the Exendin-4 analogue.

The invention discloses a novel anti-tumor nano-drug carrier and a preparation method and application thereof. The method comprises the following steps: carrying out an amidation reaction on chitosan and deoxycholic acid to form a copolymer chitosan-deoxycholic acid, forming an intermediate of the chitosan-deoxycholic acid and formaldehyde, carrying out a reaction on the intermediate and polyethylene glycol, carrying out an amidation reaction on the obtained chitosan-deoxycholic acid-polyethylene glycol so as to prepare the novel anti-tumor nano-drug carrier. The characteristics that a folate receptor on the surface of the tumor cells has high expression and the folate receptor hardly has excessive expression in normal tissues are utilized, the novel anti-tumor nano-drug carrier connected with folate and the tumor cells have high affinity, and the defect that the common nanoparticle function is single is overcome. The prepared novel anti-tumor nano-drug carrier can well avoid cytophagy of phagocyte, the carrier circulates in vivo for a long time and is not eliminated, the active targeting modification can be better combined with tumor cell specificity, and the harm of the drug to normal human cells is reduced.

The invention relates to glucagon-like peptide 1 (GLP-1) analogues with a long-acting effect and a synthesis method thereof. GLP-1 analogues with longer pharmacological action time are obtained through replacing / modifying 17th, 26th, 34th and 37th amino acids of natural GLP-1, the synthesis of target polypeptides is quickly realized through a microwave-promoted solid-phase synthesis method, and crude products are purified and freeze-dried to obtain the GLP-1 analogues.

The invention relates to a type of Glucagon-likepeptide1 and the use thereof. The structure of the Glucagon-likepeptide1 derivatives is presented in the following formula. The invention also provides a medical salt, a solvolyte, a chelate or a non-covalent complex formed by the compounds shown by the structure, a prodrug based on the compound, or any mix of the above form. The chemical property of the compounds provided in the invention is stable, unlikely to be degraded by IV (DPP-IV) in body. When used for decreasing blood glucose concentration in body, the compound or the drug adopting the compound as an active ingredient have relatively long plasma half-life (above 30 hours) and an significant effect in decreasing blood glucose concentration. X, in the formula, is selected from glycin or glycinamide.

The invention discloses a method for preparing enoxaparin sodium, comprising the steps of salinizing, drying, esterfying, alcohol precipitating, oxidizing, alcohol precipitating, fine filtering and freeze drying. In the method provided by the invention, a hydrophilic liquid phase reaction, a hydrophobic liquid phase reaction and a solid phase reaction are adopted, so that macromolecule sodium heparin is degraded into micromolecule sodium heparin with a specific structure, and the molecular weights of products and molecular weight distribution ranges are controlled, thus anti-FIIa activity resulting in bleeding risk is greatly reduced, the anti-FXa activity is relatively improved, and the product effectiveness and safety advantages are obvious. The enoxaparin sodium can be used for effectively preventing venous thromboembolism and pulmonary embolism, can be used for thrombosis before and after operations of orthopedic surgery and neurosurgery, and can be used for greatly reducing apoplexy risk, more effectively reducing death, cardiac failure and recurrent angina of patients suffering from unstable coronary artery syndromes, reducing hypertriglyceridemia and effectively eliminatingthe side effects of haemorrhage, osteoporosis and induced thrombocytopenia after long-term use of common unfractionated heparin sodium and derivates of common unfractionated heparin sodium.

The invention relates to a folic acid-mediated (polyethylene glycol) PEG-graphene oxide doxorubicine-loaded nanoparticle and a preparation method thereof. The preparation method includes carrying out functional modification on graphene oxide with folic acid and PEG, and loading a model drug doxorubicine. According to the invention, the drug loading capacity of the nanoparticle is increased, drug targeting property is improved, and the half-life of plasma and mean residence time are remarkably prolonged, so as to improve the curative effect of doxorubicine. The invention can reduce the toxic and side effects of doxorubicine, and prolong the drug resistance time and improve drug targeting property, so as to enhance the antitumor effect of doxorubicine. The invention has important clinical significance for some medicaments with wide antitumor spectrum but severe adverse effect and high toxicity.

The invention relates to an albumin bounding type 5-fluorouracil prodrug, and applications thereof in anti-tumor drug transfer. The prodrug is a compound formed by bridging 4-maleimidobutyric acid, 6-maleimidocaproic acid or 8-maleimido octanoic acid and N1-hydroxymethyl-5-fluorouracil through an ester bond, wherein the maleimido group is adopted as a bonding target of free sulfydryl of 34-site cysteine of albumin. The prodrug compound can be rapidly specifically bonded with albumin in blood to form an albumin prodrug composite, and therefore the drug metabolism speed is reduced, drug half life is significantly prolonged, and a long circulation function is achieved. In addition, under EPR effects and albumin acceptor mediation, tumor targeting is achieved and antitumor effects are improved. The 5-fluorouracil prodrug is used for intravenous injection and has a wide market application prospect.

The following invention is directed to macromolecules having controlled stoichiometry and topology, processes for their production, and applications for their use. The macromolecules have a controlled functional moiety stoichiometry and include at least one dendritic motif having a surface layer formed from at least one surface building unit and at least one subsurface layer formed from at least one building unit, the surface building unit and building units having a hydrocarbon backbone bearing a carbonyl group and at least one amine group; and at least two different functional moieties on the building unit and / or surface building unit; where functional moiety stoichiometry refers to the number and type of functional moieties.

The compositions disclosed herein are of use for the treatment of a wide variety of diseases. In particular, the compositions provide oxytocin and oxytocin analogs in sustained release formulations. In particular embodiments, the disclosed compositions concern oxytocin and oxytocin analogs, each of which may be associated with a biodegradable polymer and / or attached to a hydrophilic polymer. The methods include treatment of a wide variety of diseases and conditions. In particular, the methods include treatment of sexual dysfunction and disorders associated with repetitive behaviors, such as autism. The usefulness of the present invention is that the oxytocin, oxytocin analogs and mixtures thereof can be administered in a pharmaceutical formulation that increases their half-life and also provides for sustained release.

Methods for treating sepsis of acetaminophen-induced liver damage in a subject sing a haptoglobin derivative are provided. Compositions containing a haptoglobin derivative for treating sepsis of acetaminophen-induced liver damage are provided.

The invention relates to novel long-acting glucagon-like peptide 1 (GLP-1) analogues and a synthesis method thereof. GLP-1 analogues with longer pharmacological action time are obtained through replacing / modifying 17th, 26th, 34th and 37th amino acids of natural GLP-1, the synthesis of target polypeptides is quickly realized through a microwave-promoted solid-phase synthesis method, and crude products are purified and freeze-dried to the GLP-1 analogues.

The invention discloses a gamboges acid nanometer particle preparation and is prepared by the components of raw material gamboges acid 0.05 to 1.5 percent, polylactic acid 0.05 to 1.5 percent, surfactant 0.1 to 1.5 percent, organic solvent 33 to 50 percent and the allowance of water with the following steps: dissolving the polylactic acid into the organic solvent and dispersing the gamboges acid in the mixed solution of the polylactic acid and the organic solvent; the preparation is obtained by adding the mixed solution with the gamboges acid into water phase with the surfactant, stirring magnetically for 4 hours, vacuum distillation and filtering with a 0.22Mum micro-porous filtering film after the organic solvent and part of water are distillated. The drug with a clear system, the particle size between 10 to 100nm and good dispersion and stability can significantly solubilize drugs, has a targeting effect for reticuloendothelial cells and concentrate at lesion sites, thus improving the curing effect of the drug and reduces the side effect of the drug. Additionally, the drug has a slowly releasing effect, can maintain constant plasma concentration or pharmacologic effect for a long time and improve drug bioavailability.

The invention provides a nanocrystal composition of a slightly-soluble antitumor drug, i.e., camptothecin and derivatives thereof, and a preparation method thereof. According to the invention, an optimized alkali-dissolution acid-precipitation high-pressure-homogenization process is employed; drug powder is subjected to alkali dissolution and then acid is added at a gradient speed to allow a nanocrystal to be precipitated; acid precipitation is carried out in two steps, and a produced salt is removed through a centrifugation step; and high-pressure homogenization is carried out to further decease a particle size. Preferably, the camptothecin nanocrystal has an average particle size of 100 to 150 m and is uniformly distributed; the camptothecin nanocrystal can be preserved for a long time in the form of freeze-drying powder only by adding a minute quantity of poloxamer 188 as a freeze-drying protection agent; and in use of the camptothecin nanocrystal, a glucose solution with a concentration of 5% is added and shaken out, so the camptothecin nanocrystal directly recovers to a state before freeze-drying. The method is simple, good in repeatability and suitable for large-scale production. The prepared nanocrystal has good slow release effect; and compared with commercially available injections, the nanocrystal has prolonged circulation time in blood plasma, improves distribution of the drug in human tissue and has beeter antineoplastic effect and good development prospects.