197results about How to "Good membrane permeability" patented technology

This invention provides methods of loading preformed liposomes by transmembrane permeation induced by alcohols. Solutes loaded into liposomes by this ethanol mediated process include both small nonpolar molecules and larger species, such as proteins and carbohydrates.

The invention belongs to the technical field of medicines and discloses cytarabine 5'-O-amino-acid ester, pharmaceutically acceptable salts thereof and a preparation method thereof. The preparation method comprises the following steps of: slowly dropping carbobenzoxy chloride into a solution formed by cytarabine, sodium bicarbonate and N,N-dimethylacetylamide, and obtaining a compound A after reacting at room temperature; using the compound A and N-butyloxy formoxyl-amino acid as raw materials; adding a reagent to the solution to carry out an esterification reaction to obtain the cytarabine 5'-O-amino-acid ester; and then adding acid to obtain a finished product. The pharmaceutically acceptable salts comprise hydrochlorides, sulfates, formates, acetates, mesylates, propionates, butyrates, p-toluene sulphonates, phosphates, bisulfates, maleates, lactates, carbonates, bicarbonates, malonates, and salts formed with acidic amino acids, and the like. The invention can obviously improve the membrane permeability of the cytarabine so as to improve the bioavailability of the cytarabine.

The invention discloses a group of tenofovir disoproxil compounds with activity for inhibiting HIV-1/HBV virus replication and pharmaceutically acceptable salts thereof, and a preparation method and pharmaceutical applications thereof. The group of the compounds have a general formula I, wherein X=H, Y=H, R1=-CH2(CH2)mCH2O(CH2)nCH3, m=0-4, n=10-20, and R2, R3 and R4 are respectively described in the specification. The invention also discloses a pharmaceutical composition containing the group of the compounds. Experiments show that one of the compounds has the advantages that an activity for inhibiting HIV-1 virus replication is 20 times that of a positive control medicine zidovudine (AZT), 1,000 times that of TDF that is the best medicine for treating Aids and about 9 times that of CMX157 in a clinical stage, and lipid solubility is about 2 times that of CMX157. Experiments also show that the compounds provided by the invention have the activity for inhibiting HBV virus replication, and can be used for development of drugs for treating the Aids and hepatitis B.

A uniform microfluidized nanoemulsion is disclosed containing an anti-cancer agent, such as dacarbazine. The microfluidized nanoemulsion improves the combination's cell membrane permeability by at least four-fold over conventional nanoemulsion compositions, which significantly increases the intracellular concentration of anti-cancer agents. As a nanoemulsion, dacarbazine has a greater anti-cancer efficacy than when applied as a free solution.

The invention belongs to the field of micro-molecular fluorescence probe, and especially relates to a near-infrared fluorescence probe used for detecting zinc ions in a water phase, a preparation method thereof, and an application thereof in biological living cell detections. The structural formula of the near-infrared fluorescence probe used for detecting zinc ions in the water phase is represented by the following, wherein X is halogen, perchlorate, nitrate, or bisulfate. When the fluorescence probe provided by the invention is subject to a reaction in a water phase with zinc ions, the fluorescence emission intensity is enhanced. Therefore, the probe is advantaged in good selectivity, high sensitivity, and the like. The emission peak of the fluorescence spectrum is in the near-infrared zone, such that the probe is advantaged in low cytotoxicity and good cell membrane permeability. The fluorescence probe provided by the invention can be used in intracellular zinc ion detection and fluorescence imaging.

The invention relates to a lysosome targeted fluorescent probe as shown in a structural formula and used for lactam ring leuco body regulation and control. The fluorescent probe responds to weakly acidic environment (with pH of 4-6) in a highly sensitive and highly selective manner in a complex buffer solution through lactam ring OFF-ON allosterism. Fluorescent confocal imaging experiments of the probe show that the probe can recognize lysosomes in tumor cells in a targeted manner and has certain promising application prospect in the diagnosing of diseases such as cancers.

The invention discloses a rhodamine B targeted lysosome pH fluorescent probe with a cysteine ethyl ester structure, wherein the rhodamine B targeted lysosome pH fluorescent probe has the structure as shown in a formula (I). Meanwhile, the invention discloses an application of the probe as a living cell lysosome pH fluorescent probe. Experiments show that the probe provided by the invention does not generate fluorescence under the neutral and alkaline conditions, the fluorescence intensity is rapidly enhanced along with the reduction of the pH value of the solution, is up to the maximum value when the pH value is about 4.0 and is enhanced by about 150 times when the pH value ranges from 7.51 to 3.53, and the probe has favorable antijamming capability and reversibility in the presence of various metal ions. An intracellular colocalization experiment and an interlysosome pH regulation experiment prove that the probe can specially mark a lysosome and sensitively monitor the small change of the interlysosome pH value. A cell survival rate experiment shows that the probe is nontoxic to cells, which indicates that the probe disclosed by the invention has an important application value in the aspects of imaging the cells and monitoring the change of the interlysosome pH value.

Methods and devices are provided for the rapid and specific detection of target microorganisms, cells, and the like. In one embodiment, the methods involve contacting a target microorganism (e.g., in a sample) with a permeabilization reagent that selectively permeabilizes or lyses the microorganism; contacting the selectively permeabilized microorganism with a detection reagent that is taken into the selectively permeabilized organism or that contacts metabolites or enzymes released by the selectively permeabilized microorganism, where the detection reagent produces a signal in the presence of said metabolites or enzymes; and detecting a signal produced by the detection reagent in the presence of the metabolites or enzymes wherein the strength of the signal indicates the presence and/or amount of the target microorganism in the sample.

The invention discloses a fluorescent probe and a manufacturing method thereof and application of the fluorescent probe in detection on ribose nucleic acid (RNA). The probe has a thiazole orange styrene structure which is shown in a chemical structural formula (I) (please see the formula in the description) and is simple and stable in structure and easy to manufacture. The probe can be used for specific detection on RNA, wherein RNA in a solution can be quickly detected through a fluorespectro photometer or directly through visual inspection under fluorescent lamp irradiation; the probe also can be used for detecting or labeling or displaying existence and distribution of RNA in living cells. The fluorescent material has the efficient and specific recognition capacity on ribose nucleic acid (RNA), has the advantages of very good cell membrane permeability, low photoinduced toxicity, biotoxicity and light bleaching property and the like and overcomes the defects that other detection methods are high in cost and equipment requirement, relatively complex in technical operation and the like.

The invention discloses acyclic nucleoside compounds with an HIV-1/HBV viral replication inhibition activity, preparation methods thereof, and antiviral applications thereof. The invention also discloses a general formula I of the compounds. R1 is hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C5-6 aryl, or C5-12 aralkyl. R2 is a side chain of any natural or pharmaceutically acceptable amino acid. When the side chain contains carboxyl, the carboxyl is esterified optionally by using alkyl or aryl. The invention also discloses preparation methods of the compounds represented by the structural general formula I and a structural general formula II, and medicine compositions comprising the compounds. As a result of experiments, the compounds provided by the invention have the activity of inhibiting HIV-1/HBV viral replication. One of the compounds has activity higher by more than 385 times that of a current AIDS-treating medicine tenofovir disoproxil fumarate (TDF), and higher fat-solubility than TDF. The compounds can be used in developments of medicines used for treating AIDS or hepatitis B.

The invention discloses novel application of a cyanine dye to viable cell mitochondria G-quadruplex detection. The cyanine dye is a structural compound shown as a formula (I) or a stereoisomer of thecompound shown as the formula (I). A cyanine dye fluorescent probe has advantages of high biocompatibility, low cytotoxicity, low molecular weight and low biological sample damages, and real-time observation of cell samples can be realized without being affected by pH values of cells.

The present invention relates to recombinant fragments of C. difficile TcdA and TcdB that may be used in the development of vaccines against C. difficile associated disease. More particularly it relates to combinations comprising a ToxB-GT antigen and a TcdA antigen or a ToxA-GT antigen and a TcdB antigen.

The invention discloses a fluorescent probe and application thereof. The fluorescent probe is provided with a structure shown as a formula I or a stereoisomer of the fluorescent probe, wherein R1 is hydrogen, alkyls of C1 to C6, phenyl or alkyl-substituted phenyl; R2 to R9 are independent hydrogen atoms, alkyls of C1 to C6, halogenated alkyls of C1 to C6 and alkoxys or hydrogen atoms of C1 to C6;R10 and R11 are independent sulfo or sulfo-substituted alkyls of C1 to C6; X1 and X2 are independent carbon, oxygen, sulfur, selenium or tellurium. The fluorescent probe has the specific advantages ofgood biocompatibility, low cytotoxicity, small damage to a biological sample and good photobleaching resistance; long-time effective observation of a cell sample can be realized without influence from a pH value of a cell.

The invention discloses a superfine drymeal granule suitable for pulmonary administration and a preparation method thereof. The drymeal granule has good air-atomizing property. With smaller geometric dimension, the drymeal granule can deposit in the alveolus area to maximum extent, so the active molecule of the medicine has higher bioavailability. In addition, the drymeal granule can be used for DNA and RNA lung administration. The invention is also designed to introduce how to use volatility salt to prepare the superfine drymeal granule with good air-atomizing property. The invention solves the technique defects of the over size of the drymeal granule, the low density of the granule, inconvenient application and easy inactivation of active drug ingredients caused by the sharp decline of the air-atomizing property resulting from the water absorbability in the lung superfine drymeal granule prepared by the existing drymeal preparation technique. Meanwhile, the invention also solves the problem that the drymeal produced by the spray drying technology which is developed by Nektar Company, U.S.A, has relatively small deposition rate in the alveolus area and can not be used for transmitting protein, peptide or nucleic acid drugs containing DNA and RNA, and the like, caused by relatively small granule size and relatively high granule density.

The invention relates to nimodipine lyophilization dry emulsion for injection. Before freeze-dried or reconstituted, according to percentage concentration per 1000 ml of fat emulsion, the lyophilization dry emulsion contains 0.001 percent to 0.2 percent of nimodipine, 0.5 percent to 30 percent of oiliness solvent, 0.1 percent to 5 percent of emulsifier, 5 percent to 40 percent of the freeze-drying protective agent and 0.1 percent to 10 percent of isotonic regulator. The invention also relates to a preparation method of nimodipine lyophilization dry emulsion. The invention has the advantages that ethanol is avoided to decrease irritation; the product can be mixed with any proportion of water for injection, sodium chloride solution, glucose solution, blank fat emulsion or other aqueous solution without phenomena of precipitation or crystallization; in addition, compared with the fat emulsion, the lyophilization dry emulsion is more helpful to improve the stability of nimodipine and excipient of the nimodipine, thereby lowering the requirements of production, transportation and storage conditions and prolonging the period of validity.

The invention discloses a pyrrole pyridine salt fluorescent probe used for RNA (ribonucleic acid) and nucleolus imaging in a living cell. The structural general formula of the fluorescent probe is shown in a formula (I), wherein R<1> and R<2> represent an alkyl group, a hydroxyalkyl or an ether group. The invention also discloses application of marking or displaying distribution of RNA and nucleolus in the living cell and identifying life or death state of the cell of the fluorescent probe. The probe has the characteristics of wide application scope, good membrane permeability and low cytotoxicity and can be used for specific fluorescence imaging of RNA in the living cell.

The invention discloses a solid dispersion body of a berberine-phospholipid complex and a preparation method thereof and belongs to the field of pharmaceuticals. The lipid solubility of berberine is low, the absorbing capability of a permeable membrane is poor, and the berberine is a substrate of P-glycoprotein (P-gp) and is expelled by epithelial cells on the stomach and intestine to result in the extremely low oral bioavailability, so that an effective method needs to be adopted to improve the lipid solubility of the berberine, meanwhile, the expelling of P-glycoprotein is inhibited, and further the drug absorption is promoted. The solid dispersion body of the berberine-phospholipid complex disclosed by the invention consists of berberine, phospholipid, vitamin E polyethylene glycol succinic acid ester and silicon dioxide in a certain weight ratio, and has the advantages that the lipid solubility of the berberine is improved, the expelling of P-glycoprotein is inhibited, the drug is promoted to be absorbed by the gastrointestinal tract, the bioavailability is improved, the stability and the flowability are good, the preparation method is simple and convenient, and the great industry prospect is provided.

Cyclodextrin compound therapeutics to reduce age-related non-bisretinoid lipofuscin in a patient having a buildup of same, said method comprising administering 2-hydroxypropyl-β-cyclodextrin, or its derivatives, or β-cyclodextrin or its derivatives, or α-cyclodextrin or its derivatives, or γ-cyclodextrin or its derivatives in an amount effective to reduce non-bisretinoid lipofuscin levels. The methods include treating and/or preventing aging of the skin, muscle and other tissues and organs, which may result in increased life-span or health-span.

The invention belongs to the technical field of medicine and relates to a preparation method of a carrier prodrug with intestinal novel organic cation transporter 2 (OCTN2) being a target point.The preparation method includes the step of design of a prodrug structure with L/D-carnitine for modifying anti-tumor medicine containing hydroxyl or an amino group through a linker arm.The series of prodrug can improve the oral bioavailability of medicine.The invention relates to an L/D-carnitine derivative shown in the general formula I and the general formula II and pharmaceutically acceptable salt or hydrate or solvate or the pharmaceutically acceptable prodrug.Drug and R have definition given by the specification (please see the formula in specification).

A method of cleaning filtering membranes with a cleaning chemical includes steps to partially or completely purge and refresh the cleaning chemical in an area at or near the membrane surface or in or near the membrane pores. A liquid cleaning chemical is provided in contact with a first side of the membranes. A portion of the cleaning chemical is moved towards a second side of the membranes by a transmembrane pressure. Some or all of the cleaning chemical in the pores of the membranes is purged by supplying a pressurized gas to the second side of the membranes. An amount of fresh cleaning chemical is then moved towards the first side of the membrane. Additional steps of purging and refreshing chemical cleaner may be performed.

The invention belongs to the field of medicinal preparations and clinical medicine and relates to an antibody nucleic acid drug conjugate with dual enzyme-sensitive properties, a preparation method ofthe conjugate and an application of the conjugate. The antibody nucleic acid drug conjugate has a structure shown as A-m-X-Y-B, wherein A is an antibody, X is a cell-penetrating peptide in covalent linkage with the A through an oligopeptide m, Y is a flexible chain section in covalent linkage with the X, and B is a nucleic acid drug in covalent connection with the Y. The antibody nucleic acid drug conjugate achieves universality, and can serve as a transfer system for various nucleic acid drugs and provide theoretical support and technical reference for further clinical translation. Besides,the antibody nucleic acid drug conjugate can also serve as an in-vitro screening drug. According to different in-vitro screening aims of different drug researches, the antibody nucleic acid drug conjugate can serve as a positive control or a negative control.

Embodiments of the invention include the treatment of amyloid oligomer toxicity by administering a membrane sealant co-polymer, for example poloxamer 188 (P188).