68results about How to "Good cell membrane permeability" patented technology

The present invention provides compounds that inhibit Factor XIa and methods of preventing or treating undesired thrombosis by administering a compound of the invention to a mammal. The invention also provides three-dimensional structures of Factor XIa and methods for designing or selecting additional Factor XIa inhibitors using these structures.

Pesticidal concentrate and spray compositions are described which exhibit enhanced efficacy due to the addition thereto of a compound which increases cell membrane permeability, suppresses oxidative burst, or increases expression of hydroxyproline-rich glycoproteins.

The invention provides a fluorescence dye using fluorescein as matrix, and a preparation method and application thereof. The fluorescence dye using fluorescein as maternal has the structure in general formula I. The fluorescence dye is used for biological dyeing, and simultaneously one of the dyes is applied to external and internal detections of cysteine, and meanwhile is applied to in vivo detection and other fields. The compound has a certain level of water-solubility, and simultaneously has good cell membrane permeability. The compound of the present invention simultaneously has novel spectrum characteristics, and the fluorescein derivative dyes with good properties are applied to the aspect of the fluorescence imaging.

The invention provides a fluorescence-labeled O6-benzyl guanine. A 1,3,5,7-tetramethyl-8-butyryl-BODIPY fluorescent group is introduced into a para-position or a meta-position of benzyl of O6-benzyl guanine through ether coupling chains of different lengths. The invention provides a small molecular fluorescent probe for marking functional MGMT (O6-Methylguanine-DNA Methyltransferase) proteins in living cells. Probe molecules are covalent inhibitors designed according to the catalyzing mechanism of MGMT, have high cell membrane permeability, can be used for inhibiting MGMT in cells and performing fluorescence labeling on the MGMT, and can be applied to preparation of probe molecules for marking living MGMT in living cells. A structural general formula is shown in the specifications.

The invention relates to a near infrared fluorescence probe adopting nile blue as a parent, a preparation method thereof and applications thereof. The fluorescence probe has a structure shown as the general formula I as the attached drawing 1. The fluorescence probe can effectively improve deficiencies of tumor labeling fluorescence probes at present, can sensitively and accurately response to target cells COX-2 expression amount of which is abnormal, and is suitable for effective specific near infrared fluorescence probes labeling living tumor cells. The fluorescence probe provided by the invention is simple in synthesis and products are easy to obtain. The fluorescence probe provided by the invention has a very low fluorescence background in non-tumor cells and high fluorescence signals in tumor cells, and has strong specific labeling function for tumor cells. In addition, compounds of the type have good cell membrane permeability, low biotoxicity, low phototoxicity and low photobleaching capability and can locate a special organelle of a certain kind tumor cell.

The invention discloses a benzothiazole lysosome-targeted pH fluorescent probe and preparation and application thereof. A preparation method of the probe comprises the steps that quinoline-4-formaldehyde, 2-methyl-benzothiazole and trimethylchlorosilane (TMSCl, serving as a catalyst) are dissolved into dimethylformamide according to the mole ratio of 1:1:10 in a sealed tube, the solution is heated to 100 DEG C, a reaction is conducted for 16 hours, and precipitates are filtered out; the precipitates are dissolved with dichloromethane, the pH value is regulated to be 8.0 with a NaCO3 solution, extraction is conducted with dichloromethane, drying and recrystallizing are conducted, and the pure product is obtained. The probe has the large Stokes displacement (110 nm) and has the high sensitivity and selectivity on H<+> changes. The pKa value is 3.52, and the pH linear range is 3.0-3.8. A laser co-focus experiment shows that the probe can be positioned to a lysosome in a targeted mode and makes a response for pH changes of the lysosome in a weak acid environment. In addition, the probe can detect pH changes in escherichia coli in a highly acidic environment (the pH value is smaller than 4) in a highly sensitive mode.

The invention discloses a Pu'er tea yeast fermentation technology. The technology comprises the following steps: (1) cleaning, (2) fermentation, (3) tea overturning, (4) stacking, (5) natural drying and (6) refining. According to the invention, Pu'er tea leaves are fermented in a fermentation room with the assistance of yeast, so that the cell membrane permeability of the Pu'er tea is increased, the enzymatic oxidation of polyphenols substances is promoted, the quality of the Pu'er tea is enhanced and the contents of water extracts, tea pigment, amino-acid and the like of the Pu'er tea are increased; as the Pu'er tea is produced through the adoption of the yeast fermentation technology, the fermentation time is distinctly shortened and the production efficiency is improved. The Pu'er tea, produced by adopting the yeast fermentation technology, is bright in color, full in shape, attractive in appearance, rich and strong in scent and rich in nutrition; the Pu'er tea water has a sweet and faint fragrance and is palatable; color, fragrance, taste, shape and nutrition of the original tea leaves are kept.

The invention discloses recombinant escherichia coli of a temperature-control coexpression exogenous gene, which is named as Escherichia coli DT26 (pBVNsS) CCTCC NO:M 209018. The genotype of the recombinant escherichia coli is delta nagE::FRT; and the recombinant escherichia coli contain a temperature-control coexpression carrier pBVNsS. Simultaneously, the invention also discloses the application of the recombinant escherichia coli used as a catalyst for the complete cell catalytic preparation of N-acetylneuraminic acid. In the process of the large-scale catalytic production of the N-acetylneuraminic acid, the recombinant escherichia coli of the temperature-control coexpression exogenous gene has the characteristics of safe and convenient preparation of the catalyst, simple operation of the catalytic process, cheap price, higher efficiency, easy extraction and the like.

The invention discloses an application of naphthyl derivatives used as targeted pH fluorescent probes for mitochondria, and specifically discloses targeted marking of 1- methyl-4-[2-(6-hydroxyl-2-naphthalene)- vinyl]-pyridium (HNEP<+>) in the mitochondria of living cells, and an application thereof in pH detection. The derivatives are excited at a wavelength of 390nm, and achieve maximum fluorescence emission at a wavelength of 586nm. The fluorescence intensity at a wavelength of 586nm is gradually weakened with the rising of the pH value from 5.00 to 11.50 in a phosphate buffer system. The pKa value is 8.8, and the linear range of the pH value is 7.8-10.0 and suitable for detection for the mitochondria in an alkaline environment (with a pH value of 8.0). In addition, the probes have an ultra-large Stokes displacement (196nm), and are high in selectivity and water solubility, low in toxicity and beneficial to fluorescence imaging study in the cells. A colocalization experiment in the cells and a pH adjustment experiment for the mitochondria prove that the probes are capable of realizing specific targeted marking for the mitochondria, and capable of detecting the change of the pH value in the mitochondria with high sensitivity.

The invention discloses a dinuclear ruthenium (II) complex as well as a preparation method and an application thereof as a living cell fluorescent dye. The dinuclear ruthenium (II) complex is characterized in that the cation part of the dinuclear ruthenium (II) complex is [(phen)2Ru(L)Ru(phen)2]<4+> and the structural formula is shown as the formula I in the specification; and the anion part of the dinuclear ruthenium (II) complex is (ClO4)<1-> or Cl<1->. The dinuclear ruthenium (II) complex has excellent fluorescent characteristics and good cell membrane permeability, is a good living cell imaging reagent, simultaneously has bigger two-photon absorption interface, can color cytoplasm in the living cells without cell pretreatment and has good resistance to bleaching and a simple and stable structure. Cell viability experiment results show that the complex has lower cytotoxicity, causes slight cellular damage, has high coloring sensitivity and strong cell permeability and has great application potentials as a long-time single / two-photon cell imaging dye and a biological probe.

The invention discloses a carbazole ratio-dependent pH fluorescence probe, a preparation method of the probe and application of the probe to testing the change of extreme acidic pH in living cells and escherichia coli. The preparation method comprises the following steps: under the protection of inert gas, dissolving N-ethyl carbazole-3-formaldehyde (or a derivative thereof) and a 1,1-dialkyl-2-methyl-1H-benzo-indole-[e] derivative into absolute ethyl alcohol, performing a heating reflux reaction to prepare a crude product by taking piperidine as a catalyst; and concentrating the crude product, and performing silica gel column separation to obtain a pure product. The probe shows a ratio emission fluorescence characteristic under extreme acidic conditions and meanwhile has the advantages of high sensitivity and favorable selectivity for H+, large Strokes displacement and the like. Besides, the probe can penetrate a cytomembrane to mark a cell and is suitable for testing the change of extreme acidic pH in cells and escherichia coli.

The invention discloses a fluorescent dye, a synthesis method and application thereof. The structure of the fluorescent dye is shown as formula (1). The invention provides a novel PH stable membrane permeable xanthene dye with biologically relevant application potentials. The fluorescent dye has high synthesis yield, can keep fluorescence open in an aqueous phase with PH of 4-10, and has very good photophysical and chemical properties, and the hydroxyl position of xanthene and the carboxyl position of spiro lactone can easily be modified to generate biologically related tracers. After modification of the carboxyl position of spiro lactone by hydrazine, a derivative (i.e. compound 5) can achieve significant selective recognition on mercury (shown as the attached figure), thus being able to serve as a very good mercury detection fluorescent probe. In addition, benefiting from a very wide range of PH application and good film permeability, the dye can be applied to lysosomes and other acidic organelles to serve as a detection and recognition gene, thus having important application value. (formula 1).

Specific binder-drug conjugates (ADCs) of kinesin spindle protein inhibitors, effective metabolites of these ADCs, processes for preparing these ADCs, the use of these ADCs for the treatment and / or prevention of diseases and to the use of these ADCs for preparing medicaments for treatment and / or prevention of diseases, in particular hyperproliferative and / or angiogenic disorders such as, for example, cancer diseases, are described.

The invention discloses a preparation method of a pyracantha fortuneana fruit extract. The preparation method comprises the following steps of: (1) enzymolysis: taking pyracantha fortuneana fruits, and adding a compound enzyme for enzymolysis to obtain an enzymolysis mixture; (2) alcohol extraction: adding ethanol into the enzymolysis mixture for carrying out extraction, and carrying out filtering and concentrating to obtain an ethanol extract; (3) macroporous adsorption resin purification: loading the ethanol extract on macroporous adsorption resin for purification, and collecting a desorption solution; and (4) drying: concentrating and drying a decomposition and precipitation solution to obtain the product. The preparation method has the advantages that flavone in the pyracantha fortuneana fruit can be effectively extracted, industrial production can be easily realized, and the pyracantha fortuneana fruit extract with the effects of resisting oxidation, brightening and whitening is obtained.

The invention relates to the field of disinfectants, in particular to a botanical disinfection composition. The botanical disinfection composition comprises the following raw materials in parts by weight: 0.5-1.0 part of tea tree essential oil, 0.5-1.0 part of niaouli essential oil, 0.5-1.0 part of palmarosa essential oil, 0.5-1.0 part of lemon mint essential oil, and 0.3-0.8 part of lemon myrtle essential oil and / or litsea cubeba essential oil. The invention further provides a method for preparing the botanical disinfection composition, comprising uniformly mixing tea tree essential oil, niaouli essential oil, palmarosa essential oil, lemon mint essential oil, and lemon myrtle essential oil and / or litsea cubeba essential oil according to predetermined parts by weight. The botanical disinfection composition provided by the invention is low in usage amount of ethanol, small in toxic and side effects, good in sterilization effect and short in action time.

The invention discloses a 4-N substituted anthracene pyridone fluorescent dye and a preparation method and application thereof. The compound has the structural general formula I, wherein in the general formula I, n is an integer from 1-10; and R is selected from hydrogen atom, methyl, hydroxyl, amino group, dimethylamino group, trimethyl ammonium halide group and guanidine hydrochloride group. The 4-N substituted anthracene pyridone fluorescent dye disclosed by the invention is simple to synthesize, and has good light stability, relatively long emission wavelength and good cellular membrane permeability. Therefore, the invention also aims to provide application of the 4-N substituted anthracene pyridone fluorescent dye in biological dyeing, and the 4-N substituted anthracene pyridone fluorescent dye can be used for dyeing fixed cells, living cells and biological tissues.

The invention discloses membrane permeability dye with a large two-photon fluorescence active cross section. The dye adopts triphenylamine heterocyclic chemical compounds, and the chemical structure of the dye is shown in the formula (I). The invention further discloses an application of the dye in displaying two-photon imaging of cytoplasm in a living cell. Experiments show that the dye has characteristics of larger two-photon fluorescence active absorption cross section, excellent cell membrane permeability, low toxicity and the like, also has the characteristics of wide application range, low price and good bio-compatibility with known probe DAPI (4',6-diamidino-2-phenylindole) and has wide application prospect in the field of laser excitation fluorescence biomarkers.

An object of the invention is to provide a peptide having a stabilized secondary structure.The present invention provides a peptide having a secondary structure stabilized by a crosslinked structure and containing at least one combination of a special amino acid of the formula (I):(wherein, (A) represents a single bond or a linking group having, in the main chain thereof, from 1 to 10 atoms; (B) represents a group containing at least one π bond; (C) represents a hydrogen atom or an alkyl group which may be substituted with a substituent; and X represents a group substitutable by a substitution reaction with a sulfanyl group) and an amino acid having, in the side chain thereof, a sulfanyl group; and having the crosslinked structure formed through a thioether bond between the side chain of the special amino acid residue and the sulfanyl group.

The invention discloses a pseuoginsenoside F11 phospholipid complex as well as a preparation method and application of the pseuoginsenoside F11 phospholipid complex and belongs to the field of pharmaceutic preparations. The preparation method of the pseuoginsenoside F11 phospholipid complex comprises the following steps of: dispersing phospholipid in a hydrophilic carrier solution with a certain concentration, then adding pseuoginsenoside F11 to obtain a mixture, and then grinding the mixture into a suspension solution with the particle size being smaller than 1000nm, wherein the medicine, namely the pseuoginsenoside F11 and the phospholipid mutually act to form a phospholipid compound. The pharmaceutic liposolubility of the prepared phospholipid compound is increased, the permeability of the prepared phospholipid compound on cell membranes is increased, and therefore the bioavailability of the pseuoginsenoside F11 is greatly improved; the phospholipid compound can be prepared into quick-release pellets; and the activity of the prepared pseuoginsenoside F11 quick-release pellets is remarkably improved. No organic solvent is used in the preparation process, so that the environmental pollution is avoided and the production safety is improved.

The invention provides a composite nanomaterial of organic naphthalene and inorganic phosphate, and the composite nanomaterial has the structure of general formula I shown in the description. The composite nanomaterial can perform identification, adsorption, clearance and transport of the heavy metal in the living cell, and can show obvious different identification signals in the adsorption process of the heavy metal in the living cell. The material has a certain level of water solubility, has good membrane permeability, and has low biotoxicity, phototoxicity, and photobleaching property. The spectral region of the material has enough large difference with the spectral region of the biological sample.

The present inventors have found that when screening for cyclic peptide compounds that can specifically bind to a target molecule, the use of a library including cyclic peptide compounds having a long side chain in the cyclic portion can improve the hit rate for cyclic peptide compounds that can specifically bind to the target molecule. Meanwhile, the present inventors have found that tryptophan and tyrosine residues, which have conventionally been used in oral low molecular-weight pharmaceuticals and are amino acid residues having an indole skeleton or a hydroxyphenyl group, are not suitable for peptides intended to attain high membrane permeability.

The invention discloses a novel near-infrared fluorescent compound for specific detection of hydrazine, wherein the near-infrared fluorescent compound is (E)-2-(2-(3-(dicyanomethylene)-5,5-dimethylcyclohexyl-1-ene-1-yl)vinyl)-5-(diethylamino)phenyl 4-bromobutyric acid and is capable of specifically detecting hydrazine in an organism. The near-infrared fluorescent compound is simple in preparationprocess, readily available in raw materials, low in cost and stable in structure, has relatively good cell membrane permeability and relatively low cytotoxicity, can enter living cells and animal tissues and react with exogenous hydrazine to generate strong red fluorescence which can be distinguished by naked eyes; ultraviolet absorption and fluorescence spectrophotometry analysis shows that the near-infrared fluorescent compound has excellent selectivity to hydrazine under various interferents and has quite strong anti-interference capability to common biomolecules; the novel near-infrared fluorescent compound not only can selectively recognize exogenous hydrazine, but also can quantitatively detect hydrazine with high sensitivity in the growth environment of various living cells, and issuccessfully applied to imaging of living cells and zebra fishes.

The invention discloses plant mask and a preparation technology thereof. The plant mask is prepared from the following components in parts by weight: 24 to 30 parts of plant extract, 8 to 10 parts ofphytosterol, 15 to 25 parts of plant modified SOD (Superoxide Dismutase), 5 to 6 parts of vitamin C ethyl ether, 13 to 15 parts of butylene glycol, 4 to 5 parts of sarcosine, 3 to 7 parts of inositol,0.8 to 1.6 parts of niacinamide, 16 to 22 parts of sodium pyrrolidonecarboxylate, 4 to 8 parts of xanthan gum, 6 to 8 parts of hyaluronic acid, 3 to 5 parts of coenzyme Q, 4 to 6 parts of ceramide, 0.6 to 1.4 parts of dipotassium glycyrrhizinate, 6 to 10 parts of cross-linked silk fibroin fibers and 50 to 70 parts of de-ionized water, wherein the cross-linked silk fibroin fibers are of a base material of the plant mask and is a coupled product of cocoon fiber silk fibroin fibers and glycerin triglycidyl ether. The plant mask disclosed by the invention takes natural plant components, vitamin or skin matrix components as the raw materials, is healthy and has no pollution; any allergic or irritating effect is not generated so that the plant mask is suitable for people with various skin typesand has relatively strong moisturizing, repairing, whitening and anti-oxidization functions.

A method of treating a patient having an inflammation, infection from bacteria or molds or fungi or virus or cancerous cells by destroying bacteria or molds or fungi or virus or cancerous cells is disclosed. The method comprising the step of directing one or more sound wave treatments into the patient targeting the inflammation, infection, mold, virus, bacteria or fungi to cause a body to identify these as foreign objects and trigger the body's own natural healing mechanisms to destroy the foreign objects.

The invention belongs to the field of treatment by targeting drugs, and discloses a prodrug with tumor targeting and a preparation method and application of the prodrug. The structural formula of theprodrug is GEM-FA, GEM is gemcitabine, FA is folic acid or an analogue of the folic acid, and the GEM and the FA are coupled through an amido bond; the inhibiting effect of the prodrug on multiple kinds of tumor cells is 3-5 times better than that of the original drug, the toxicity of the prodrug to a normal liver cell LO2 is lowered by about three times, and the in-vitro cell transport of the prodrug does not depend on expression of nucleic acid transport carrier protein, which is beneficial for reducing drug resistance of the gemcitabine. Compared with the original drug, the prodrug GEM-FA after intravenous injection can maintain higher concentration, higher AUC content and longer half-life period of the gemcitabine medicine in a body. The prodrug has the characteristic of folate receptor-mediated tumor cell targeting, can solve the problems that the gemcitabine is low in anticancer targeting, and the phenomena of deamination and passivating and drug resistance easily occur, and hasan effect of removing cancer cells through metabolism of targeting antagonistic tumor cells and the like.

The invention belongs to the field of targeted drug therapy, and discloses a gemcitabine prodrug with tumor targeting properties and a preparation method and application thereof. The structural formula of the prodrug is GEM-B, wherein GEM represents gemcitabine, B represents biotin, and NH2 of GEM is coupled with COOH of B through an amide bond; the prodrug has better inhibiting effects on varioustumor cell strains, the IC50 value of the prodrug is 5-7 times lower than that of GEM, but the toxicity of the prodrug on normal hepatocytes is 3-4 times or more lower, in-vitro cell transport of theprodrug does not rely on expression of nucleic acid transport carrier proteins, and thus drug resistance of GEM can be reduced. Compared with the drug prototype, the prodrug can maintain higher in-vivo gemcitabine concentration, larger AUC and longer half-life after being injected. The prodrug has the advantage of tumor targeting mediated by biotin receptors, and the defects can be overcome thatgemcitabine is low in targeting and easy to deaminize and passivate and easily causes drug resistance; and effects of eliminating tumor cells by targeting metabolic pathways antagonistic to the tumorcells are achieved.

The invention relates to the field of medicinal chemistry and in particular relates to garcinia triazole derivatives (9), a preparation method of the derivatives and medical application of the derivatives in pharmacy. R1, R2 and n are defined as the specification. The derivatives are structural analogues of a garcinia natural product, namely gambogic acid, have the antitumor effects and can be used for preparing antitumor medicines. The structural formula is as shown in the specification.

The invention discloses a polypeptide for carrying out targeting on mitochondria, and a preparation method and application of the polypeptide. The polypeptide is briefly recorded as MTPs. The polypeptide, which is prepared by the scheme of the invention, for carrying out the targeting on the mitochondria has a simple in synthesis method, and the obtained polypeptide can specifically carry out targeting on the cell mitochondria, is almost non-toxic to cells, has good cell membrane penetration characteristics, can be conveniently subjected to further multifunctional derivative modification, and provides a potential delivery tool for preparation of mitochondrial targeting drugs.