188 results about "Peptide drug" patented technology

Methods and apparatus for protein and drug design using multicapitate (“two or more headed”) neural networks, wherein one head, a sequence head, is trained to generate the sequence of a protein, and another head, a structure head, is trained to generate the structure of the protein; and wherein the neural network is configured to accept a representation of a specified condition as input, and output a representation of a protein's sequence and structure. The structure head and sequence head each have their own loss functions, and the weights of the neural network body are shared, and jointly updated during training. Non-limiting examples of specified input conditions include representations of associated proteins and / or sets of properties of the desired output protein. Some embodiments of the invention include for the design and synthesis of effective peptide drug ligands, synthetic biologic antibody drugs, antibody drug conjugates, and monoclonal antibody (mAb) drugs.

Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and / or proteins. The covalently modified peptides and / or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

The invention belongs to the field of biological medicines, particularly relates to an oral polypeptide composition system capable of being stably absorbed in gastrointestinal tracts, and particularly discloses an oral polypeptide composition which comprises polypeptide molecules (A), a surfactant (B) and an amino acid single-molecule or double-molecule combination (C), the molecular weight of the peptide medicine used as the medicine in the oral polypeptide composition is in the range of 0.1 kDa to 20 kDa. The acting part of the composition system is small intestine or large intestine; the stability and absorbability of the polypeptide composition in gastrointestinal tracts are obviously improved and enhanced.

Provided are a sustained-release microsphere for polypeptide drugs, a pharmaceutical formulation thereof, a method for preparing same, and use thereof. The method comprises the following steps: forming an inner aqueous phase; forming an oil phase; forming an outer aqueous phase; and dispersing the inner aqueous phase into the oil phase to give a primary emulsion, then re-dispersing the primary emulsion into the outer aqueous phase to give a pre-secondary emulsion, emulsifying the pre- secondary emulsion to form a secondary emulsion, and finally curing the secondary emulsion to give the sustained-release microsphere. The method features ease to operate, and the obtained sustained-release microsphere possesses ideal drug release behaviors (low early burst release, and stable mid- and later-stage releases) and safety and potency in reducing blood glucose, and is thus suitable for stable, long-term use with good patient compliance.

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a thrombopoietin peptidomimetic peptide diagram detection and analysis method which comprises the following steps: (1) performing buffer system replacement on thrombopoietin peptidomimetic through ultrafiltration centrifugation; (2) carrying out enzymolysis on the thrombopoietin peptidomimetic by adopting trypsin; and (3) detecting and analyzing the enzymolysis peptide fragment by using a reversed-phase high-performance liquid chromatography. The method disclosed by the invention has the beneficial effects that sample concentration and buffer solution replacement are performed through the ultrafiltration tube, and the sample subjected to enzymolysis is high in purity and can be directly detected by using reversed-phase high-performance liquid chromatography, so that the method for detecting and analyzing the peptide diagram of the thrombopoietin peptidomimetic is simple and convenient to operate, and the detection efficiency of thrombopoietin peptidomimetic drugs is improved; by controlling the chromatographic conditions, the accuracy and precision of high performance liquid chromatography detection are improved, and the quality analysis and control of thrombopoietin peptidomimetic drugs can be realized.

The invention belongs to the field of biological medicine, and particularly relates to a galactose modified liver targeting mesoporous silica material, a preparation method and application. Mesoporous silica is prepared through a hydrothermal synthesis method, modification is carried out through amino, disulfide bonds, graphene quantum dots and amino-terminated PEG chain galactose, a multifunctional drug carrier (PEG-Gal-MSNs-SS-GQDs) with the redox response release function is prepared, meanwhile, leech active peptide GFAGDDAPRA (GA-10) is loaded into a mesoporous channel, liver targeting release of drugs is achieved, and the liver targeting effect is achieved. The material loaded with the GA-10 has good redox response release characteristics and blood fat reducing activity. The PEG-Gal-MSN-SS-GQDs disclosed by the invention have a wide application prospect, and a new thought is provided for research on application of mesoporous silica in peptide drug loading and blood fat reduction.

The invention discloses an anti-aging compound polypeptide solid-in-oil nanosuspension for external use and a preparation method thereof, and belongs to the technical field of medicines. The compound polypeptide solid-in-oil nanosuspension comprises a water-soluble polypeptide drug, a surfactant and an oil phase matrix, the water-soluble polypeptide drug is wrapped by the surfactant, and is uniformly dispersed in the oil-phase matrix after being freeze-dried to form the compound polypeptide solid-in-oil nanosuspension; the water-soluble polypeptide drugs comprise snake venom-like tripeptide, acetyl hexapeptide-8, acetyl tetrapeptide-9, acetyl tetrapeptide-11 and palmitoyl pentapeptide-4, and the average particle size of the drugs in the compound polypeptide solid-in-oil nanosuspension is smaller than 300 nm. The compound polypeptide solid-in-oil nanosuspension has the advantages of being stable in anhydrous phase, good in permeability, high in encapsulation efficiency, good in activity and the like, and is suitable for percutaneous delivery of hydrophilic drugs; the prescription of the solid-in-oil nanosuspension does not contain water, so that the preparation of a stable polypeptide preparation is facilitated, and the solid-in-oil nanosuspension is convenient to store; the composition can be used for anti-aging cosmetics.

The invention discloses a polypeptide drug chimera and a preparation method thereof, and belongs to the technical field of polypeptide drug carriers. The polypeptide drug chimera is constructed by a recognition segment specifically combined with a target protein and a functional polypeptide carrier mediating the target protein to be transferred to lysosome; an antibody is combined with a lysosome signal amino acid sequence, and pathogenic antigen protein is transferred into a lysosome subcellular organelle for degradation through specific combination of the antibody and different antigens.

The invention belongs to the technical field of big data analysis, and particularly relates to a polypeptide drug pharmacokinetic data analysis platform based on artificial intelligence, which comprises a data collection module, a preprocessing module, a prediction analysis module, a joint verification module and a visual output module. Clinical data collected and processed by the data collection module and the preprocessing module are trained through the prediction analysis module, so that the established model has real data support, and the reliability of the artificial intelligence analysis model is ensured; meanwhile, the joint verification module compares the artificial intelligence analysis model obtained through training with an existing experimental data result and a model structure, and perfects the artificial intelligence analysis model through a model iteration mechanism; the accuracy and authenticity of the analysis result output by the artificial intelligence analysis model are further ensured through multi-dimensional verification, so that reliable technical support is provided for research and development of new drugs.

The present invention provides an ionizable lipid and a drug delivery system comprising the ionizable lipid. Specifically, the present invention provides an ionizable lipid having a structure of formula (I), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof. Lipid nanoparticles constructed by using the ionizable lipid can realize safe and efficient delivery of nucleic acid drugs, small molecule drugs, peptide drugs and protein drugs.

The invention discloses a scallop skirt ACE inhibitory peptide activity method and system based on deep learning, and relates to the technical field of bioengineering.The scallop skirt ACE inhibitory peptide activity method comprises the steps that a comprehensive data set is obtained based on simulated in-vivo test data and peptide level feature data of different peptides, key features are screened, and a training set and a test set are divided; initializing a random forest model, an SVM model and a logistic regression model, performing independent training by using the training set, and determining an optimal prediction model of the peptide antihypertensive activity based on a prediction result of the test set; extracting importance data of key features based on the optimal prediction model for the antihypertensive activity of the peptide, sorting the importance data, and visually analyzing the antihypertensive activity features, feature importance sorting and model performance of different peptides; and all key results in the analysis process are integrated and systematically stored. According to the method, normal form reference with prediction accuracy and mechanism depth can be provided for clinical transformation of marine bioactive peptides, and AI-driven novel peptide drug research and development are promoted to enter a new stage.

The invention belongs to the technical field of biological medicine, and relates to an oral peptide drug delivery system based on a soybean trypsin inhibitor and core-shell hydrogel, the oral peptide drug delivery system comprises therapeutic polypeptide, KTI and a core-shell structure gel matrix, and the problems that an existing oral peptide delivery system is passively protected and drug burst release is remarkable are solved. A chitosan / sodium tripolyphosphate ionic cross-linked network forms an inner core, a sodium alginate / calcium ion'egg box 'structure cross-linked network forms a shell, and therapeutic polypeptides such as liraglutide and KTI are jointly embedded. Through the pH response characteristic and sequential release design of the core-shell structure, KTI is preferentially and rapidly released in the intestinal environment to inhibit local protease activity, then therapeutic polypeptide is slowly released, and active protection and synergistic interaction are achieved. The invention further provides a specific preparation method and parameters. The polypeptide has the advantages of stable structure in a gastric acid environment, targeted release in intestinal tracts, high encapsulation efficiency, capability of avoiding burst release and the like, and provides a new strategy for efficient delivery of oral polypeptide drugs.

This invention provides an application of the peptide Nod-T3 in the preparation of drugs for treating lung diseases. The Nod-T3 peptide is derived from human protein and has a significant inhibitory effect on chronic lung inflammation and fibrosis caused by smoking. It can be used to treat COPD and other smoking-related lung diseases. It also has high biocompatibility and low toxicity, and has the potential and development value to become a new type of peptide drug.

A peptide sequence mimicking endogenous cofilin-1 incorporates transmembrane amino acid sequences to enhance cellular uptake of the peptide drug. When cofilin peptide drugs are introduced into cancer cells, they affect cancer cell migration and invasion abilities. Furthermore, the peptide sequence can be conjugated with a chelator for cancer diagnosis.

This invention discloses a GLP-1 peptide drug microneedle and its preparation method. The microneedle is composed of PVP, NVP, a photoinitiator, and a GLP-1 receptor agonist. The preparation method includes two steps: material preparation and peptide microneedle patch preparation. First, a certain amount of PVP is dissolved in NVP to prepare a solution with appropriate specific gravity and viscosity. Then, the photoinitiator and GLP-1 receptor agonist are added to the solution to form a liquid system that is as uniformly suspended as possible. Second, the suspension is filled into a microneedle mold, and NVP is polymerized into solid PVP by ultraviolet light irradiation. Under the constraint of the mold, the solid PVP forms the geometric shape of the microneedle. Subsequently, a small amount of NVP is spread evenly on the backing layer of the microneedle and covered with a plastic film. Ultraviolet light irradiation is applied again to crosslink the plastic film with the PVP microneedle, and the microneedle is then peeled out of the mold. The advantage of this application is that it uses PVP to prepare an NVP solution with suitable specific gravity and viscosity, so that the subsequently added drug is uniformly suspended in the solution, thereby improving the uniformity of drug loading on microneedles and increasing the drug loading capacity, which is beneficial to improving the efficacy and consistency of drug efficacy.

The invention discloses a method for detecting polypeptide sequence difference and post-translational modification thereof based on a nanopore system, the nanopore system is constructed in the method, and the nanopore system comprises an alpha-hemolysin nanopore and octa-amino modified gamma-cyclodextrin embedded in the nanopore; the amino acid sequence of the alpha-hemolysin nanopore comprises mutation sites M113R and T145R, and the alpha-hemolysin nanopore is characterized in that the alpha-hemolysin nanopore According to the detection method, polypeptide with negative charges enters a nanopore under the driving of external voltage, an ion current blocking signal is recorded, and the polypeptide sequence difference and post-translational modification are analyzed according to blocking amplitude, duration, noise characteristics and event frequency. The method can detect a peptide chain with the length of 2-10 amino acid residues, can distinguish the post-translational modification state in homopolypeptide composed of 4-10 amino acids and polypeptide by single amino acid resolution, and can be used for protein enzyme digestion product analysis, oligopeptide drug detection and rapid polypeptide identification under the condition of no mass spectrum.

This invention discloses a brush-like peptide drug delivery system, its preparation method, and its applications, belonging to the fields of polymer chemistry and biomedicine. The method includes modifying the amino acid residues of a peptide drug with active functional groups through click or cycloaddition reactions; reacting the modified peptide drug with a polydisulfide backbone through click or cycloaddition reactions to obtain a brush-like peptide drug; and performing charge shielding and bioactivity modification on the lysine residues in the brush-like peptide drug to obtain the brush-like peptide drug delivery system. The brush-like peptide drug delivery system of this invention reduces peptide toxicity, enhances peptide targeting, improves peptide pharmacokinetics, and solves the problem of poor water solubility of some peptide drugs. It can be used in the treatment of tumors, cardiovascular diseases, neurological diseases, pathogenic bacterial or viral infections, or in the development of vaccines.

Problem The purpose of the present invention is to provide a novel method for prevention and / or treatment of opioid tolerance or opioid dependence. Specifically, the purpose of the present invention is to develop peptide-based blockers to block MOR-DOR and KOR-DOR heterodimerization. In addition, the purpose of the present invention is to develop homodimer blockers for MOR, DOR, and KOR which modulate their downstream signaling without affecting their internalization. Solution The present invention is a prophylactic and / or therapeutic agent for the prevention and / or treatment of opioid tolerance or opioid dependence comprising the peptide which inhibits the dimer formation of the opioid receptor, wherein the above opioid receptor dimer is a heterodimer or a homodimer formed from one or two opioid receptors selected from the group consisting of the μ type (MOR), the κ type (KOR), and the δ type (DOR).

This invention discloses a selenylamide-based hydrogenation reaction of acetylacetamide compounds and its application in the modification of selenium-containing peptides and proteins, belonging to the fields of organic chemistry and chemical biology. The reaction involves the reaction of a selenium-containing compound with an acetylacetamide compound in a solvent with the addition of an additive. The applications of this reaction include: 1) selective modification and labeling of selenocysteine ​​in peptides and proteins; 2) cyclization reactions of selenium-containing peptides and selenoproteins; and 3) sequential modification of selenium-containing peptides in the presence of cysteine ​​by precise pH control combined with the hydrogen sulfide reaction of acetylacetamide. This reaction has advantages such as mild conditions, simple operation, fast reaction rate, high yield, good stability, and good selectivity. It provides a new and robust approach for the selective modification and labeling of selenium groups in bioconjugations, peptides, and / or proteins, and also provides a new method for the construction of cyclic peptides, offering a powerful tool for the development of selenium-containing peptide drugs.

The application discloses a polypeptide for targeted recognition of a neuroendocrine tumor marker INSM1 and products and applications thereof, and belongs to the fields of molecular imaging and protein polypeptide drug engineering. Specifically, the application relates to development of a polypeptide with high affinity and specificity to a neuroendocrine tumor marker insulinoma-associated protein 1 (INSM1). The application discloses an amino acid sequence of the polypeptide and related applications. The polypeptide is used for labeling and preparation of a polypeptide probe, can be specifically combined with the INSM1 protein, and can be used for in-vivo and in-vitro imaging of neuroendocrine tumors, so as to overcome a diagnosis difficulty caused by a hidden onset of the neuroendocrine tumor and realize early positioning and qualitative diagnosis.

The present application relates to an oral polypeptide composition system stably absorbed in the gastrointestinal tract, and specifically discloses an oral polypeptide composition. The composition comprises a polypeptide molecule (A), a surfactant (B), an amino acid monomolecular or a bimolecular combination (C). The molecular weight of a peptide drug used as a drug in the oral polypeptide composition is within a range of 0.1 kDa to 20 kDa. The action part of the composition system is small intestine or large intestine; and the polypeptide composition has obviously improved and increased stability and absorbability in the gastrointestinal tract.

Provided, as an anti-SARS-CoV-2 peptide drug, is an optimal salt form of a peptide that binds to a receptor-binding domain (RBD) in SARS-CoV-2.　A sodium or potassium salt of a peptide according to the present invention has, in a direction from an N-terminus to a C-terminus, a first region including a first helix and a second region including a second helix. The first region and the second region each include a site that binds to a receptor-binding domain (RBD) in SARS-CoV-2. A bond is formed between amino acid residues within five residues on the N-terminus side in the sequence of the site that binds to the receptor-binding domain (RBD) in SARS-CoV-2 in the first region and amino acid residues within five residues on the C-terminus side in the sequence of the site that binds to the receptor-binding domain (RBD) in SARS-CoV-2 in the second region, and the peptide binds to the receptor-binding domains (RBD) in SARS-CoV-2.

The invention discloses a method for determining whole-body biological distribution of protein polypeptide drugs, and belongs to the technical field of in-vivo tracking of drugs. Comprising the following steps: mixing a protein polypeptide drug and a fluorescent dye with an NHS group, adding a pH buffer agent without a free amino group, maintaining the pH value of the mixed solution at 7.5-8.5, incubating, and purifying to remove redundant dye so as to obtain a fluorescence labeled product; imaging after in-vivo administration of the fluorescence labeling product, and obtaining the whole-body biological distribution condition of the protein polypeptide drug according to the fluorescence intensity obtained by imaging; or after the fluorescence labeling product is administrated in vivo, blood samples are collected at multiple different time points, fluorescence scanning is carried out, the blood concentration of the protein polypeptide medicine is obtained through calculation, and the whole-body biological distribution condition of the protein polypeptide medicine is obtained. According to the method provided by the invention, the determination process does not need radioactive substances, pollution reagents are not generated or used, and the method is safe and environment-friendly.

Among hospital–acquired infections, Pseudomonas aeruginosa-associated urinary tract infections (UTIs) are mainly caused by indwelling urethral catheters (catheter-associated UTIs or CAUTIs) and are difficult to treat, resulting in high rates of morbidity among hospitalized patients. While antibiotics can successfully treat bacteria in the bladder lumen, they are inefficient at crossing stratified urothelium plasma membranes to kill persistent intracellular bacterial communities (IBCs). Herein, UTI IBCs are targeted by locally delivering the antibiotic gentamicin and / or the steroid hormone estradiol via polymeric nanogels conjugated with a cell-penetrating peptide Cys-Gly-Lys-Arg-Lys (CGKRK - SEQ ID NO:1). This approach delivered more intracellular gentamicin compared to drug delivered in solution in vitro and more estradiol compared to conventional methods. In an acute UTI murine model, the nanogel cell-penetrating peptide drug delivery system facilitated the transport of gentamicin into the urothelium and resulted in > 90% clearance of a uropathogenic P. aeruginosa clinical strain in vivo.

The application relates to the technical field of biological medicine, and particularly provides a pharmaceutical composition containing a peptide drug active molecule and an application thereof. The pharmaceutical composition comprises a peptide drug active molecule and a drug delivery molecule, and the weight ratio of the peptide drug active molecule to the drug delivery molecule is 1:(1-500); the drug delivery molecule is selected from a structure as shown in formula (I) or a pharmaceutically acceptable salt thereof. The application provides an application of the pharmaceutical composition in preparing an oral dosage form drug. The peptide drug active molecule is significantly improved in stability and permeability in a gastrointestinal fluid by being compounded with the drug delivery molecule, so that gastrointestinal absorption of the peptide drug active molecule is increased and oral bioavailability of the peptide drug active molecule is improved.

This invention relates to a non-natural methionine and its synthesis method, using inexpensive and readily available transition metals as catalysts. N Using arylglycine, styrene compounds, and disulfides as raw materials, a series of non-natural methionine compounds were obtained with high selectivity and high yield through a three-component reaction under mild conditions. The compounds prepared in this invention are multifunctional non-natural methionine derivatives, representing a novel class of natural methionine derivatives. They can be used in drug modification, biosensor fabrication, and other fields, possessing significant research and application value and providing new synthetic strategies for the preparation of novel peptide drugs.

The invention discloses an endogenous polypeptide medicine JM2 and application of a target spot of the endogenous polypeptide medicine JM2 in tumor treatment, and relates to the field of biological medicine. The polypeptide drug JM2 is small in molecular weight and easy to absorb, has no obvious toxicity in a cellular level experiment, and has good drug development value and clinical application prospect. The polypeptide medicine JM2 disclosed by the invention has good activity of inhibiting tumor cell proliferation, so that the polypeptide medicine JM2 is used as a tumor inhibitor to help to control growth and diffusion of tumors. The polypeptide medicine JM2 disclosed by the invention has an efficient macrophage phenotype repolarization function, and can generate a remarkable proinflammatory reaction and generate stronger anti-tumor activity, which is possibly crucial for improving the tumor recognition and removal capability of an immune system. The method can be further used for developing infectious diseases and has a wide application prospect.

The present invention relates to the field of target recognition technology, and specifically discloses a method and system for identifying polypeptide drug membrane filtration pollution using a convolutional neural network, wherein the method comprises the following steps: obtaining an image to be identified and a corresponding image sequence; generating a corrected image sequence including the corrected image to be identified; inputting the corrected image to be identified in the corrected image sequence to obtain a high-resolution feature map and a low-resolution feature map; analyzing local area characteristics of the corrected image to be identified to generate a weight parameter group; weightedly fusing the high-resolution feature map and the low-resolution feature map according to the weight parameter group to generate a fused feature map; performing target detection based on the fused feature map to generate a pollution identification result; the method effectively addresses the problems of slight shaking and detail loss under complex imaging conditions, thereby achieving accurate identification of slight pollution targets, having better robustness, being able to effectively identify slight pollution targets, and reducing false alarm and omission rates.

The disclosure provides peptide products comprising a peptide covalently attached to a surfactant moiety which have improved properties, including increased duration of action and bioavailability. The peptide products are useful for treating insulin resistance, diabetes, obesity, metabolic syndrome and cardiovascular diseases, and conditions associated therewith, such as NASH and PCOS.

A cationic lipid analogue, a composition and a use thereof. An aldehyde, an amine, a carboxylic acid and an isonitrile are adopted as raw materials to synthesize a cationic lipid analogue via the Ugi reaction. The synthesized cationic lipid analogue, together with a sterol, an auxiliary lipid and a polyethylene glycol lipid derivative, further forms a nanoparticle-like lipid composition, which can be used for drug delivery, including the delivery of small molecule drugs, nucleic acid drugs such as mRNA, DNA, siRNA, etc., protein / peptide drugs, and gene editing complexes such as mRNA / sgRNA, Cas9 / sgRNA, etc. The nanoparticle-like lipid composition achieves mRNA expressions in different organs of animals through different administration methods, and thus can meet the application requirements of mRNA nucleic acid therapies, nucleic acid vaccines, gene editing, etc.