54 results about "Morpholino" patented technology

The invention discloses a preserving fluid for stably preserving sample DNA at normal temperature and a preparation method thereof, and belongs to the technical field of biological sample preservation. The preserving fluid comprises a lysis system, a nucleic acid protection system and a buffering and stabilizing system, the cracking system comprises a composite surfactant and an enzymolysis auxiliary agent; the composite surface active agent is prepared from polyether polyol fatty acid ester and cocamidopropyl hydroxy sulfobetaine; the enzymolysis auxiliary agent comprises lysozyme Lyso-V and protease K; the nucleic acid protection system comprises a nitrogen heterocyclic polyamine-carboxylic acid derivative and dextran sulfate; the nitrogen heterocyclic polyamine-carboxylic acid derivative comprises 1, 4, 7, 10-tetraazacyclododecane-N, N ', N' ', N ''tetraacetic acid, 1, 4, 7-triazacyclononane-N, N', N''-triacetic acid, disodium ethylene diamine tetraacetate-nitrogen heterocyclic derivative, and diethylenetriamine pentaacetic acid-piperazine derivative, and the nitrogen heterocyclic polyamine-carboxylic acid derivative comprises 1, 4, 7, 10-tetraazacyclododecane-N, N ', N '', N'' tetraacetic acid, 1, 4, 7-triazacyclononane-N, N', N ''-triacetic acid. The buffering and stabilizing system comprises an amphoteric buffering agent and a polymer stabilizer; the amphoteric buffering agent comprises 2-(N-morpholino) ethanesulfonic acid and N-tri (hydroxymethyl) methylglycine.

This invention discloses a phosphorylated diamine morpholino oligonucleotide drug that regulates PAPOLA expression and its application, belonging to the field of biomedical technology. The nucleotide sequence of the drug is shown in SEQ ID NO:1, targeting the coding region of human PAPOLA mRNA. The formulation is a lyophilized powder for injection, with excipients including mannitol and phosphate buffer. This invention also discloses the application of this drug in the preparation of a treatment for gastric cancer, specifically advanced gastric cancer with high PAPOLA expression. The drug is administered intravenously at a dose of 8-12 mg / kg every 3 days. Its mechanism of action is to block PAPOLA protein translation, inhibit the G1 / S phase transition of gastric cancer cells, and induce apoptosis. In vitro and in vivo experiments have confirmed that this drug can specifically inhibit the proliferation and growth of gastric cancer cells, providing a new treatment option for advanced gastric cancer.

To provide a technique capable of recovering a normal Fukutin protein.SOLUTION: An antisense nucleic acid is a morpholino oligomer in which a range of position 2044 to position 2068 of a base sequence shown by sequence number 1 is used as a target sequence, any consists of one base sequence of the following (a) to (c): (a) a base sequence expressed by sequence number 2 or sequence number 3; (b) a base sequence having 90% or higher identity with the base sequence expressed by sequence number 2 or sequence number 3; and (c) a base sequence in which one or several bases are deleted, substituted or added in the base sequence expressed by sequence number 2 or sequence number 3.SELECTED DRAWING: Figure 14

The present invention relates to crystalline forms of (s)-1-(1-(3-chlorphenyl)-2-(dimethylamino) ethyl)-4-(5-morpholino-1h-pyrrolo [2, 3-b] pyridin-3-yl) pyridin-2 (1h)-one of the following formula (I): (I)

Described is small molecule N-(l-isopropylpiperidin-4-yl)-6-methoxy-2-morpholino-7- (3-(pyrrolidin-l-yl)propoxy)quinolin-4-amine)) (MS 1262) that inhibits methyltransferases G9a / GLP. This inhibitor can be used for the treatment of patients with G9a / GLP related diseases such as Alzheimer's Disease and Prader-Willi Syndrome.

Targeting Metabolic Pathways with MNK Inhibitors The invention belongs to the field of medicine and concerns the treatment of diseases related to aberrant upregulated de novo lipid biosynthesis using a MAPK interacting kinase (MNK) inhibitor, especially for the prophylaxis or treatment of breast cancers, prostate cancers, obesity, atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, and neurological disorders. An aspect of the invention relates to the use of an MNK inhibitor designated (4-(3-((2- (dimethylamino)pyridin-4-yl)ethynyl)pyrazolo[1,5-a]pyrimidin-5-yl)phenyl)(morpholino) methanone, for the prophylaxis or treatment of triple-negative breast cancer and brain metastases therefrom.

Novel antisense oligonucleotide conjugates that cause exon skipping in the human dystrophin gene and their use in methods of treating Duchenne muscular dystrophy (DMD) in patients suffering from the disease are described.

Provided herein are methods of using 2-(2,6-dioxopiperidin-3yl)-4-(2-fluoro-4-(3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiometer, a mixture of enantiomers, a tautomer, an isotopolog, or a pharmaceutically acceptable salt thereof, alone or in combination with obinutuzumab, for treating, preventing or managing chronic lymphocytic leukemia / small lymphocytic lymphoma.

This invention discloses a direct bilirubin assay kit and its usage method. The kit includes reagent A, reagent B, and reagent C. Reagent A contains sulfuric acid; reagent B contains 2,5-diethoxy-4-(4-morpholino)diazobenzene sulfate and sulfuric acid; and reagent C contains N,N-diisopropylethylamine and n-hexane. Using this kit, the upper limit of linearity reaches 500 μmol / L, making it suitable for the determination of higher concentrations of direct bilirubin. When measuring high-concentration samples, sample dilution is not required, reducing operational steps and minimizing the influence of human factors on the results. This kit shows no significant interference in DBIL determination when hemoglobin concentration is ≤4.5 g / L, and no significant interference in DBIL determination when triglyceride concentration is ≤40 mmol / L (P>0.05). This indicates that the kit is more suitable for the detection of lipemia and hemolyzed samples.

The invention discloses application of a quinoline compound to prevention and treatment of ralstonia solanacearum, and belongs to the technical field of prevention and treatment of plant bacterial wilt. The quinoline compound is 1-ethyl-6-fluoro-7-morpholinyl-3-(3-(p-tolyl)-1, 2, 4-oxadiazole-5-yl) quinoline-4 (1H)-ketone, and it is found for the first time that the 1-ethyl-6-fluoro-7-morpholinyl-3-(3-(p-tolyl)-1, 2, 4-oxadiazole-5-yl) quinoline-4 (1H)-ketone has very strong inhibitory activity on Ralstonia solanacearum, and the quinoline compound can be used for preparing a compound for inhibiting Ralstonia solanacearum. Experiments show that the MIC of the 1-ethyl-6-fluoro-7-morpholinyl-3-(3-(p-tolyl)-1, 2, 4-oxadiazole-5-yl) quinoline-4 (1H)-ketone to ralstonia solanacearum is 5 [mu] g / mL within 24 h, which is equivalent to that of benziothiazolinone, so that the 1-ethyl-6-fluoro-7-morpholinyl-3-(3-(p-tolyl)-1, 2, 4-oxadiazole-5-yl) quinoline-4 (1H)-ketone can be used for preventing and treating plant bacterial wilt, and a new candidate compound is provided for development of ralstonia solanacearum bactericides.

The invention relates to a nitric oxide donor based on heparin sodium and a preparation method and application thereof, the method comprises the following steps: (1) dissolving heparin sodium in a 2-(N-morpholino) ethanesulfonic acid buffer solution, adding an activator, and carrying out a reaction to obtain a reaction solution A; (2) adding beta-mercaptoethylamine into the reaction solution A, and continuously reacting to obtain a reaction solution B; (3) dialyzing the reaction solution B to obtain a solution C; and (4) adding tert-butyl nitrite into the solution C, and reacting to obtain the heparin sodium-based nitric oxide donor. Wherein in the step (1), the activating agent is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide or hydrochloride of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. According to the prepared heparin sodium-based nitric oxide donor, the nitric oxide release time is prolonged, and the problem that the half-life period of nitric oxide is short is solved.

To provide virus-like particle drug conjugate formulations and use of the conjugates for treating ocular tumors or lesions.SOLUTION: The present disclosure provides, in some aspects, ophthalmic compositions comprising a virus-like particle (VLP) drug conjugate comprising photosensitive molecules conjugated to capsid proteins of a VLP and 2-(N-morpholino)ethanesulfonic acid (MES) or a pharmaceutically acceptable salt thereof. Surprisingly, the particular MES-based formulations provided herein eliminate visible aggregation and precipitation of the VLP drug conjugate, relative to other formulations tested, in some embodiments, without at a low salt concentration and / or with a pH that is suitable for ophthalmic administration (e.g., less than 7, such 6.5).SELECTED DRAWING: None

The present application relates to a kind of heparin sodium-based nitric oxide donor and its preparation method and application, the method includes the following steps: (1) heparin sodium is dissolved in 2-(N-morpholino) ethanesulfonic acid buffer solution, adding activating agent, reaction is carried out, and reaction liquid A is obtained;(2) to reaction liquid A, continue to react to obtain reaction liquid B by adding β-mercaptoethylamine;(3) reaction liquid B is dialyzed, and solution C is obtained;(4) to solution C, nitrous acid tert-butyl ester is added, and the heparin sodium-based nitric oxide donor is obtained by reaction;Wherein, in step (1), the activating agent is 1-ethyl-3-(3-dimethylaminopropyl) carbonyl diimide or its hydrochloride salt.The heparin sodium-based nitric oxide donor prepared in the present application prolongs the release time of nitric oxide, and solves the problem of short half-life of nitric oxide.

Provided are a liquefying agent and the use thereof, and a nucleic acid detection system. The liquefying agent comprises a strong base, acetylcysteine, and 2-(N-morpholino)ethanesulfonic acid. In the liquefying agent, the concentration of the strong base is 0.2-1 mol / L; the concentration of the acetylcysteine is 3-300 mmol / L; and the concentration of the 2-(N-morpholino)ethanesulfonic acid is 2-5 mmol / L. By means of the synergistic effect of the strong base, acetylcysteine and 2-(N-morpholino)ethanesulfonic acid, the liquefaction time can be significantly shortened, thereby improving the efficiency and speed of treating viscous biological samples. Furthermore, the viscous biological samples treated with the liquefying agent can be directly used for nucleic acid amplification and have a long storage period. Long-term stability ensures the accuracy and reliability of nucleic acid detection, thereby enhancing the credibility of detection results.

The present invention relates to antisense oligonucleotides (ASO) for use in treating, preventing, or ameliorating the progression of conditions such as type 2 diabetes mellitus (T2DM) and insulin resistance, leptin resistance, and obesity, Rater Syndrome, and cancer. Specifically, a thiomorpholino-containing ASO targets a protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene transcript and induces exon skipping (including exon 2) of the transcript during RNA processing, thereby inhibiting expression of the protein tyrosine phosphatase-1B (PTP1B) protein.

This invention discloses a preservation solution for preserving sample DNA at room temperature and its preparation method, belonging to the field of biological sample preservation technology. The preservation solution comprises: a lysis system, a nucleic acid protection system, and a buffering and stabilizing system; the lysis system comprises a complex surfactant and an enzymatic hydrolysis aid; the complex surfactant comprises: polyether polyol fatty acid ester and cocamidopropyl hydroxysulfonate betaine; the enzymatic hydrolysis aid comprises lysozyme Lyso-V and proteinase K; the nucleic acid protection system comprises: nitrogen-heterocyclic polyamine-carboxylic acid derivatives and dextran sulfate; the nitrogen-heterocyclic polyamine-carboxylic acid derivatives comprise: 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''tetraacetic acid, 1,4,7-triazacyclononane-N,N',N''-triacetic acid, disodium ethylenediaminetetraacetate-nitrocyclic derivative, and diethylenetriaminepentaacetic acid-piperazine derivative; the buffering and stabilizing system comprises: an amphoteric buffer and a polymeric stabilizer; the amphoteric buffer comprises: 2-(N-morpholino)ethanesulfonic acid and N-tris(hydroxymethyl)methylglycine.

A perfusion stock composition, for preserving a donor organ for transplantation, comprising: a source of 60 to 100 mM Na+; a source of 10 to 20 mM K+; a source of 5 to 10 mM Mg2+; a source of 0.25 to 0.75 mM Ca2+; 10 to 40 mM Tris(hydroxymethyl)aminomethane hydrochloride (Tris or THAM), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 3-(N-morpholino)propanesulfonic acid (MOPS), 2-(N-morpholino)ethanesulfonic acid (IviES), N,N-bis-(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), or N / -tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES); a source of 10 to 30 mM HCO3; 1 to 30 mM glucose; 1 to 20 U / L insulin; 1 to 10 mM fructose diphosphate or a salt thereof, 1 to 40 mM aspartate or glutamate; 1 to 10 mM adenosine, cAMP or cGMP; 1 to 10 mM reduced glutathione; and 30 to 100 mM lactobionate or mannitol; and, optionally, a diluent. The present disclosure also provides a perfusion composition, a kit, a method, and a perfusion apparatus, each related to the perfusion stock composition.

The present invention relates to the technical field of organic synthesis, and specifically relates to a synthesis process of sodium 3-(N-morpholino)-2-hydroxypropanesulfonate, which includes Step 1: Dissolve MOPSO in process water to form a mixed solution, and heat it up to obtain a reaction solution; Step 2: Under an inert gas, dropwise add a sodium ion lye to the reaction solution, and then keep the temperature for reaction; Step 3: Control the pH value of the reaction system and continue to keep the temperature for reaction; Step 4: After filtration, cool down and centrifuge to obtain a crude product of MOPSO-Na; Step 5: Keep the temperature for decolorization to obtain a decolorized solution; Step 6: After filtering the decolorized solution, add a solvent, cool down to crystallize, centrifuge and dry to obtain the MOPSO-Na product; Step 7: After centrifugal concentration, cool down to crystallize; both the distilled solvent and the precipitated crystals can be recycled. The preparation process disclosed by the present invention is simple, can avoid the discharge of impurities and by-products caused by externally added auxiliaries, and is easy to realize the recycling of MOPSO.

The present invention relates to a solid state form of N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide, and to a method for preparing the same. Specifically, the invention discloses a solid state form of N-(2-(4-cyano thiazolidine-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide, and a preparation method of the solid state form. A corresponding pharmaceutical composition; their use in the treatment or prevention of prolyl endopeptidase fibroblast activation protein (FAP) mediated conditions; a kit; and a preparation method thereof.

A double-stranded nucleic acid complex is provided having first and second nucleic acid strands. The first nucleic acid strand includes an artificial nucleic acid and is capable of hybridizing to at least part of a target gene or a transcription product thereof and can induce exon skipping, exon inclusion and / or steric blocking to the target gene or transcription product thereof. The second nucleic acid strand includes a base sequence complementary to at least part of the first nucleic acid strand and includes at least one blocking region which is resistant to a nuclease which is present in a body fluid, and at least one cleavage region which undergoes degradation by a nuclease which is present intracellularly. The cleavage region includes two or more consecutive sugar-unmodified nucleosides.

The application provides a phosphoramidate morpholino antisense oligonucleotide for antiviral, which comprises a base sequence shown as SEQ ID NO. 1, the antisense oligonucleotide is a phosphoramidate morpholino antisense oligonucleotide, the structural formula of the phosphoramidate morpholino nucleotide monomer in the antisense oligonucleotide is shown in the following formula, Base is a base; R is N, N-dimethylamine or piperazine. The antisense oligonucleotide can be combined with a specific region in the fifth segment of viral RNA of an influenza virus, block the transcription of the viral RNA through steric hindrance, play an antiviral role, and use a PMO structure which is good in nuclease stability, high in antisense efficiency and good in water solubility, and at the same time, by introducing a piperazine group which is positively charged under physiological conditions, the PMO compound can enter the cell across the membrane, and the biological activity of the compound can be effectively enhanced.

The present invention relates to a process for the synthesis of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine in two hydrated crystalline forms and in one anhydrous crystalline form. The present invention further relates to methyl (Z)-4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)-N-cyanopiperidine-1-carbimidothioate which is an intermediate in this process.

The invention relates to the technical field of membrane transfer buffer solutions, and discloses an ice-bath-free protein membrane transfer buffer solution which comprises the following effective components: a complexing agent with the concentration of 1-3 mM, sodium hydrogen sulfite with the concentration of 0.5-1.5 mM, lauryl sodium sulfate with the mass percent of 0.1-0.2% and absolute ethyl alcohol with the volume percent of 10-30%, according to the membrane transfer buffer solution disclosed by the invention, a buffer group consisting of trihydroxymethyl aminomethane, beta-aminoethanesulfonic acid and 3-(N-morpholine) propanesulfonic acid is used, so that the buffer capacity of the electrophoresis buffer solution is remarkably improved, the membrane transfer time is shortened, and meanwhile, the relatively low heating efficiency can be maintained under the condition of relatively high current (voltage); ice bags, crushed ice and the like are not needed for cooling, so that the experiment efficiency is greatly improved.

The invention provides a myxocyprinus asiaticus individual genetic resurgence method which comprises the following steps: S1, taking a myxocyprinus asiaticus gonad tissue, cleaning, cutting into pieces, adding an L-15 culture medium containing double antibodies and a DPBS buffer solution, and centrifuging to obtain the gonad tissue; s2, performing water bath on the gonad tissues to obtain resuscitated gonad tissues; s3, digesting, filtering and centrifugally purifying the resuscitated gonad tissues to obtain germline stem cells; s4, injecting morpholino to obtain gobiocypris rarus without primordial germ cells; and S5, transplanting the germline stem cells into gobiocypris rarus juvenile fish bodies, and culturing to obtain the myxocyprinus asiaticus gametes. S6, the generated myxocyprinus asiaticus gametes are fertilized, and myxocyprinus asiaticus individuals are obtained. According to the method, the sperms of the myxocyprinus asiaticus are successfully obtained by utilizing a gonad cryopreservation and abdomen borrowing reproduction technology, and a feasible way is provided for individual genetic resurgence of rare and endangered fishes.

The present invention provides polymorphs of Bruton's tyrosine kinase inhibitors, their preparation methods, and uses. Specifically, two crystalline forms of (R)-6-((1-acryloylpiperidin-3-yl)amino)-7-fluoro-4-((2-fluoro-4-morpholinophenyl)amino)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one, their preparation methods, and uses are provided. The two crystalline forms provided by the present invention have good stability, are not hygroscopic, have improved solubility and pharmacokinetic characteristics, and the preparation method is stable and capable of large-scale production.

The present invention relates to analogs of nemorubicin bearing a series of substituents on the morpholino ring other than 2 "-OMe, as well as PNU-159, 682, which have a beneficial effect on the toxicity of toxins compared to molecules bearing the 2"-OMe group. In addition, it was found that PNU variants having a modified 2 ''-O-alkyl chain exhibit enhanced tolerance in vivo. Consequently, by modifying the 2 ''-O-alkyl group, ADC with elaborately tailored potency and tolerance can be produced, thereby increasing the administration dose of a patient, therefore the present invention relates to compounds according to Structure (1) and conjugates thereof, and pharmaceutical compositions and methods for targeting tumor cells and treating cancer.

The purpose of the present invention is to provide a novel means for delivering a phosphorodiamidate morpholino oligonucleotide (PMO). Provided is a phosphorodiamidate morpholino oligonucleotide (PMO) complex which comprises a PMO and a polyanion.

A perfusion stock composition, for preserving a donor organ for transplantation, comprising: a source of 60 to 100 mM Na+; a source of 10 to 20 mM K+; a source of 5 to 10 mM Mg2+; a source of 0.25 to 0.75 mM Ca2+; 10 to 40 mM Tris(hydroxymethyl)aminomethane hydrochloride (Tris or THAM), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 3-(N-morpholino)propanesulfonic acid (MOPS), 2-(N-morpholino)ethanesulfonic acid (IviES), N,N-bis-(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), or N / -tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES); a source of 10 to 30 mM HCO3; 1 to 30 mM glucose; 1 to 20 U / L insulin; 1 to 10 mM fructose diphosphate or a salt thereof; 1 to 40 mM aspartate or glutamate; 1 to 10 mM adenosine, cAMP or cGMP; 1 to 10 mM reduced glutathione; and 30 to 100 mM lactobionate or mannitol; and, optionally, a diluent. The present disclosure also provides a perfusion composition, a kit, a method, and a perfusion apparatus, each related to the perfusion stock composition.

The invention provides an immunosensor which takes Eu-TCPB-MOF as an energy donor and is used for NSE detection. Eu-TCPB-MOF is used as an energy donor, GO-PEI / Au is used as an energy receptor, energy can be effectively transferred due to spectrum overlapping between an ECL emission spectrum of the Eu-TCPB-MOF and an ultraviolet-visible absorption spectrum of GO-PEI / Au, so that the ECL signal intensity of the Eu-TCPB-MOF is inhibited under the RET effect, and after carboxyl is activated by 2-(N-morpholinyl) ethanesulfonic acid, the Eu-TCPB-MOF can be converted into the Eu-TCPB-MOF in the Eu-TCPB-MOF in the Eu-TCPB-MOF. Eu-TCPB-MOF is modified to the surface of a glassy carbon electrode to serve as a signal substrate, and the amount of NSE is calculated through ECL signal intensity change.

The invention relates to an oligonucleotide comprising one of the sequences selected from: (i) 5'- +T C A +G T C +T G A +T A +A G +C +T -3' (formula I); or (ii) 5'- +T C +A G T +C T G +A +T A +A G C +T -3' (formula II); wherein A, T, G and C are deoxyribonucleotide building blocks, or C is 5-methyl-2'-deoxycytidine; and wherein +T, +A, +G, and +C are bridged nucleotide building blocks and / or morpholino building blocks. Also provided are oligonucleotides and compositions comprising the same for therapeutic use.