26 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.

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)

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.

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.

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.

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 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 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 provides a method for purifying phosphoryl diamine morpholino oligonucleotide, and relates to the technical field of oligonucleotide purification. The purification method of the phosphoramide morpholino oligonucleotide comprises the following steps: carrying out ultrafiltration liquid change for the first time, carrying out ion pair reversed phase chromatography, carrying out ultrafiltration liquid change for the second time, and freeze-drying, so as to obtain the high-purity phosphoramide morpholino oligonucleotide. According to the invention, a purification process route of the phosphoric acid diamide morpholino oligonucleotide (PMO) is developed, the purity of the phosphoric acid diamide morpholino oligonucleotide (PMO) is effectively improved, the industrial requirements can be accurately met, and the development of the fields of scientific research and bioengineering is promoted.

Provided herein are methods of treating, preventing and / or managing cancers, which comprise administering to a patient 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.

The application discloses application of a quinoline compound in preventing and treating Ralstonia solanacearum, and belongs to the technical field of plant bacterial wilt prevention and treatment; the quinoline compound is 1-ethyl-6-fluoro-7-morpholino-3-(3-(p-tolyl)-1,2,4-oxadiazol-5-yl) quinolin-4(1H)-one; it is found for the first time that 1-ethyl-6-fluoro-7-morpholino-3-(3-(p-tolyl)-1,2,4-oxadiazol-5-yl) quinolin-4(1H)-one has strong inhibitory activity on Ralstonia solanacearum; experiments show that the MIC of 1-ethyl-6-fluoro-7-morpholino-3-(3-(p-tolyl)-1,2,4-oxadiazol-5-yl) quinolin-4(1H)-one on Ralstonia solanacearum is 5 mu g / mL at 24 h, which is equivalent to that of thiazolidine ketone, and the compound can be used for preventing and treating plant bacterial wilt and provides a new candidate compound for development of a bactericide for Ralstonia solanacearum.

The application provides a method for genetic reactivation of individual Procyprinus palpebrosus, comprising the following steps: S1, taking the gonadal tissue of Procyprinus palpebrosus, washing, cutting, adding L-15 culture medium containing double antibodies and DPBS buffer solution to centrifuge the gonadal tissue; S2, water-bathing the gonadal tissue to obtain recovered gonadal tissue; S3, digesting the recovered gonadal tissue, filtering, centrifuging and purifying to obtain germ stem cells; S4, injecting morpholino to obtain rare gobi-ocypris rarus with deleted primordial germ cells; S5, transplanting the germ stem cells into the body of the rare gobi-ocypris rarus juvenile to culture, and obtaining the gametes of Procyprinus palpebrosus; and S6, fertilizing the generated gametes of Procyprinus palpebrosus to obtain the individual Procyprinus palpebrosus. The application successfully obtains the sperm of Procyprinus palpebrosus by using the cryopreserved gonadal tissue and the technology of parthenogenesis, and provides a feasible way for the individual genetic reactivation of rare and endangered fish species.

This invention belongs to the field of pharmaceutical science and provides pharmaceutically acceptable salts of the compound (S)-7-(4-(1-(methylsulfonyl)-piperidin-4-yl)phenyl)-N-(morpholino-2-ylmethyl)pyrido[3,4-b]pyrazine-5-amine, their crystal forms, solvates and crystal forms, pharmaceutical compositions thereof, their preparation methods and applications.

The present invention relates to crystalline forms of MRTX0902 ((R)-2-methyl-3-(1-((4-methyl-7-morpholinopyridino [3, 4-d] pyridazin-1-yl) amino) ethyl) benzonitrile), pharmaceutical compositions comprising the crystalline forms, methods of making the crystalline forms, and methods of use thereof.

The present invention relates to pharmaceutically acceptable salts 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) wherein said salts are selected from the group consisting of hydrochloride salts, maleate salts, ethanesulfonate salts, ketoglutarate salts, malonate salts and oxalate salts. (I)

Compositions and methods for modulating Kit biological activity are provided. In some embodiments, the presently disclosed subject matter provides an antisense oligomer having 10-50 linked nucleotides, wherein the antisense oligomer targets a region of a pre-mRNA encoding Kit, and further wherein the targeted region comprises a sequence involved in splicing of the pre-mRNA encoding Kit. Also provided are expression vectors encoding the antisense oligomers disclosed herein, morpholino oligomer derivatives of the antisense oligomers of the disclosure, pharmaceutical compositions comprising the antisense oligomers, expression vectors, and / or morpholino oligomers of the disclosure, and methods for modulating splicing of Kit pre-RNA in a cell and / or tissue, inducing mast cell apoptosis, and treating diseases, disorders, and / or conditions associated with Kit expression.

This invention belongs to the field of organic chemical synthesis technology, specifically relating to an N-aminohydrazone derivative and its preparation method. The N-aminohydrazone derivative has the general structural formulas I and II, where Formula I is [formula missing], and Formula II is [formula missing], wherein Ar- is phenyl, substituted phenyl, aryl, or heteroaryl; in Formula I, the two R'; together constitute morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; in Formula II, R'; is morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; R" is ethyl, isopropyl, tert-butyl, or benzyl; and R';';'; is H or phenyl. Formula I is prepared using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, employing a "one-pot two-step" method. Using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, a photocatalyst and a metal catalyst are added to the reaction system to prepare Formula II. The N-aminohydrazone derivative provided by this invention has a novel structure, good functional group compatibility, mild preparation conditions, and simple operation.

Provided herein are salts of and solid forms comprising free base or salts of (S)- or racemic 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. Pharmaceutical compositions comprising such salts and solid forms and methods of use of such salts and solid forms for treating, preventing, and managing various disorders are also provided herein.

The present application provides solid forms of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridine-2-yl)-N-benzylacetamide, and methods of preparing and using the same.