45 results about "Cholesterol derivatives" patented technology

The present invention provides compositions containing endoxifen, formulations and liposomes of endoxifen, methods of preparation of such agents and formulations, and use of such agents and formulations for the treatment of breast cancer and other breast diseases and diseases susceptible to endoxifen. In particular, the compositions of the present invention include liposomes, complexes, vesicles, emulsions, micelles and mixed micelles of endoxifen in which the compositions further contain any of a variety of neutral or charged lipids and desirably, cholesterol and cholesterol derivatives, sterols, Z- and E-guggulsterones, phospholipids, fatty acids, vitamin D, and vitamin E. The present invention also provides methods of preparing endoxifen. The present invention provides methods for treating and preventing breast cancer and other breast related diseases by administrating novel formulations or compositions comprising a therapeutically effective amount of endoxifen.

The present invention provides compositions containing endoxifen, formulations and liposomes of endoxifen, methods of preparation of such agents and formulations, and use of such agents and formulations for the treatment of breast cancer and other breast diseases and diseases susceptible to endoxifen. In particular, the compositions of the present invention include liposomes, complexes, vesicles, emulsions, micelles and mixed micelles of endoxifen in which the compositions further contain any of a variety of neutral or charged lipids and desirably, cholesterol and cholesterol derivatives, sterols, Z- and E-guggulsterones, phospholipids, fatty acids, vitamin D, and vitamin E. The present invention also provides methods of preparing endoxifen. The present invention provides methods for treating and preventing breast cancer and other breast related diseases by administrating novel formulations or compositions comprising a therapeutically effective amount of endoxifen.

Provided is a skin irritation suppressant for transdermal preparations, having a sufficient reduction effect of skin irritation due to a drug. Also provided is a transdermal preparation comprising the skin irritation suppressant. One embodiment of the invention is a skin irritation suppressant for suppressing the skin irritation due to a drug and a pharmaceutical ingredient to be used in a transdermal preparation other than the drug, the skin irritation suppressant comprising a sterol compound selected from the group consisting of cholesterol, cholesterol derivatives and cholesterol analogs, and the drug is one or more basic drugs selected from the group consisting of tolterodine, asenapine, bisoprolol, risperidone, nicotine and citalopram, and their pharmaceutically acceptable salts.

The present invention relates to the field of pharmaceutical chemistry, and in particular to methods of preparing cholesterol,and derivatives and analogs thereof. The cholesterol derivatives include, but not limited to, 7-dehydrocholesterol, 25-hydroxycholesterol, 25- hydroxy7dehydrocholesterol and ergosterol. In the invention, phytosterol can be used as a raw material to prepare the compound shown in the formula I through microbial conversion, and then cholesterol and the derivatives and analogues thereof are prepared.

The invention belongs to the technical field of medicine and discloses a preparation method of sub-microemulsion used for the intravenous injection of polyene yew alcohol phospholipid composite. The sub-microemulsion of the polyene yew alcohol phospholipid composite is basically prepared from polyene yew alcohol, phospholipid, liquid oil, a surfactant, cholesterol, a cholesterol derivative, or / and a similar cholesterol derivative, an addition agent and water for injection according to the effective therapeutic dose. The sub-microemulsion of the polyene yew alcohol phospholipid composite provided by the invention has high medicine carrying quantity and good preparation stability; and the preparation method is simple, convenient and easy and is easy for realizing industrialization.

The present invention relates to a 25-hydroxy-7-dehydrocholesterol synthetic method, a 25-hydroxy-7-keto-cholesterol derivative is used as a raw material for mechanical milling reaction in a ball mill pot under the effect of sulfonyl hydrazide and a base in the absence of an organic solvent, and then hydrolysis reaction is performed to obtain 25-hydroxy-7-dehydrocholesterol synthetic method. According to the method, in the absence of a solvent, mechanical milling reaction is performed, no dust is spilled over in the grinding process, reaction controllability is good, reaction efficiency is high, the solvent recovery operation in the post-processing process can be avoided, operation is simplified, environmental pollution is reduced, the reaction selectivity is good, yield is high, operation is simple, cost is low, post-treatment is simple, three-waste is less, product is easy to separate, purity is high, the yield is up to 89%, the melting process is short, and the product purity is high.

The invention belongs to the pharmaceutical preparation field and relates to an alprostadil lipid compound, a micellar compound used in the injection of the alprostadil lipid compound and a preparation method of the alprostadil lipid compound. The alprostadil lipid compound and the micellar compound used in the injection of the alprostadil lipid compound are composed of alprostadil with a therapeutic dose, phospholipid, cholesterol sulfate or / and similar cholesterol derivative, additive and injection water. The alprostadil lipid compound and the micellar compound used in the injection of the alprostadil lipid compound have the advantages of small side effect, low blood vessel simulation, high drug-loading rate, narrow particle size distribution, capability of filtering and degerming, good pharmaceutical stability, etc.

The invention discloses a nucleoside analog cholesterol derivative characterized in that its structure is Nu-L-Ch, wherein Nu is a nucleoside analog group, L is a fatty chain connection group with a carbon number between 2 and 7, Ch is a cholesterol group. A highly dispersed transmission system including liposomes, nonionic surfactant vesicles, nanoparticles and microemulsion or a self-assembly transmission system can be formed from the nucleoside analog cholesterol derivative.

The invention provides a tanshinone IIA lipid compound and a micellar compound used in the injection of the tanshinone IIA lipid compound. The tanshinone IIA lipid compound is composed of tanshinone IIA with a therapeutic dose, phospholipid, cholesterol sulfate or / and similar cholesterol derivative, additive and injection water. By means of the lipidization of the docetaxel, the problem that the tanshinone IIA does not dissolve is water and then cannot be directly prepared into an injection. The tanshinone IIA lipid compound injection provided by the invention has the advantages of small side effect, low blood vessel simulation, high drug-loading rate, narrow particle size distribution, capability of filtering and degerming, good pharmaceutical stability, etc.

The invention discloses a cholesterol derivative-modified multi-molybdenum oxygen cluster hybrid. The chemical formula of the cholesterol derivative-modified multi-molybdenum oxygen cluster hybrid is[(C4H9)4N]3{(MnMo6O18)[CNH(CH2O)3O72H116N3O8]2} and is shown as the structural formula (I), wherein POM=MnMo6O18, and TBA=[(C4H9)4N]+. The cholesterol derivative-modified multi-molybdenum oxygen cluster hybrid is prepared by taking a multi-molybdenum oxygen cluster with a chemical formula of [(C4H9)4N]3(MnMo6O18)[(OCH2)3CNH2]2, 3, 3'-dicholesterol succinyl imidazole monoester dipropyl amine succinate monoamide, 1-ethyl-(3-dimethyl aminopropyl) carbondiimide hydrochloride, N-hydroxysuccinimide and trimethylamine as raw materials for reaction in a chloroform-acetonitrile mixed solvent system. The cholesterol derivative-modified multi-molybdenum oxygen cluster hybrid is applied to preparation of anti-breast cancer drugs and achieves high killing effects on human breast adenocarcinoma cell lines (MCF-7).

The invention relates to a pH-sensitive tumor targeted recombinant high-density lipoprotein, which is prepared from the following ingredients in parts by weight: 1 to 5 parts of antitumor medicine, 15to 35 parts of phospholipid, 15 to 60 parts of albumin, 1 to 10 parts of cholesterol derivatives and 2 to 6 parts of linoleic acid. The pH-sensitive cholesterol derivatives in the ingredients effectively ensure the structure stability of rHDL in the blood circulation conveying process; the targeted conveying efficiency of the antitumor medicine to the tumor tissues is improved; after the rHDL istaken by tumor cells; acetal bonds in the pH-sensitive cholesterol derivatives are hydrolyzed into the original cholesterol; the catalysis condition of intracellular ACAT enzyme is met; the fast release of the antitumor medicine in the tumor cells is realized through the lipoprotein structure change; the tumor cells are effectively killed. The lipoprotein belongs to a tumor targeted carrier with huge development potential; the problems of low bioavailability and low tumor killing selectivity of the antitumor medicine in the prior art are solved.

The invention specifically relates to a chloroquine cholesterol derivative, and a preparation method and application thereof, belonging to the field of the chemical pharmaceutical industry. The chloroquine cholesterol derivative provided by invention has a structure as shown in a formula I which is described in the specification. The invention also provides the preparation method and application of the chloroquine cholesterol derivative. The chloroquine cholesterol derivative provided by the invention can effectively inhibit the proliferation of rat fibroblasts and treat pulmonary fibrosis, exerts anti-inflammatory effect, and offers a novel option for preparation of anti-fibrotic, anti-inflammatory and anti-tumor drugs.

The invention provides a cell membrane fluorescent probe with high brightness, high stability and insensitivity to environment, particularly a naphthalimide probe which can be used for cell membrane fluorescence imaging. The fluorescent probe has the advantages of being low in synthetic raw material cost, simple in method, easy to derive and the like. Research finds that azetidine, azolidine and other high-rigidity structures are introduced to the 4-position and the 5-position of a naphthalimide parent of the dye, and the rigidity and lipophilicity of the dye are improved. The molar extinctioncoefficient of the dye in ethanol is 35000 M<-1>cm<-1> or above, the highest quantum yield can reach 0.72, and the dye has very high brightness and light stability; the dye also has environmental insensitivity, extremely small spectral property difference in different environments and good imaging accuracy; the dye structurally contains structures such as long aliphatic hydrocarbon chains or cholesterol derivatives or quaternary ammonium salts and can interact with cell membranes, so that the cell membranes can be quickly and accurately positioned, can be quickly labeled and can be applied tothe fields of cell membrane fluorescence imaging and the like.

Docetaxel and doxorubicin can be formulated in liposomal pharmaceutical compositions. In various embodiments, the pharmaceutical compositions include (i) a first liposome type comprising a first lipid layer comprising an unsaturated phospholipid, cholesterol or a cholesterol derivative, DC-cholesterol, a cationic lipid, and preferably a pegylated phospholipid, and a first active pharmaceutical ingredient (API) comprising docetaxel in the first lipid layer; and (ii) a second liposome type comprising a second lipid layer, an aqueous interior, and a second API comprising doxorubicin crystallized in the aqueous interior, (iii) where the first liposome type does not comprise doxorubicin and the second liposome type does not comprise docetaxel. The pharmaceutical composition can be used to treat a subject, for example, a human subject having cancer. The cancer can be, for example, a lung cancer, preferably non-small cell lung cancer (NSCLC), colon cancer, breast cancer, or liver cancer, preferably hepatocellular carcinoma (HCC).

The present invention concerns nanoparticle formulations suitable for the delivery of one or more therapeutic agents, the formulations comprising: a cationic cholesterol derivative; a neutral phospholipid; cholesterol or a neutral cholesterol derivative; and a saturated fatty acid, PEGylated neutral derivative of phosphatidylethanolamine or phosphatidylcholine.

A liposome formulation for stably incorporating high content of hydrophobic substance is disclosed. The liposome includes two phospholipids with different phase transition temperatures such as saturated and unsaturated phosphatidyl cholines, hydrophobic substances, cholesterol, cholesterol derivatives, antioxidant and hydrophilic polymer-modified lipids such as MPEG-DSPE.

Provided is a compound represented by the general formula (1) (where: G represents a hexose-6-phosphate residue; and L represents a divalent linker group).

The present invention describes compositions containing cholesterol-linker-glutathione conjugates for targeting the brain by overcoming barrier entry to the CNS through the blood brain barrier (BBB), including micelle and liposome forms of such compositions. In addition, methods for treating subjects by administering such compositions are also disclosed.

The invention belongs to the field of pharmaceutical preparations, and relates to azithromycin ion pair liposome eye drops and a preparation method thereof, particularly to a method for preparing azithromycin ion pair liposome eye drops from a cholesterol derivative by using azithromycin as an active component, and new uses of the azithromycin ion pair liposome eye drops in preparation of xerophthalmia treating drugs, wherein per 100 ml of the azithromycin ion pair liposome eye drops comprise 0.5-2 g of azithromycin, 5-10 g of phospholipid, 1-5 g of a cholesterol derivative, 5-10 g of an oil phase, 50-200 mg of DSPE-PEG, 1-5 mg of a preservative, and 30-80 mg of an antioxidant. According to the present invention, the azithromycin ion pair liposome eye drops load the drug by using the ion pair technology, such that the solubility and the stability of the drug in the preparation are improved, the drug loading amount is significantly increased, the azithromycin ion pair liposome eye dropscan be well used for the treatment of xerophthalmia, and the bioavailability is high.

Immunoreactive compositions and methods for immunizing animal, including, humans, cows, and fowl, against cholesterol and cholesterol derivatives, including cholesterol oxides, and their use in methods for reducing and preventing lipid raft-based diseases, including, but not limited to HIV-1, SARS, prion formation in Creutzfeldt-Jakob disease, and neutralizing oxidized modified lipoproteins, specifically, oxidized-LDL, oxidized-VLDL / IDL, and oxidized-chylomicrons, which contribute to the formation of fatty streaks and atherosclerotic plaques, are described.

The invention provides a cationic cholesterol derivative, a nano-composite as well as a preparation method and application of the nano-composite, and particularly relates to a cationic lipid gene transfection reagent. The invention relates to a preparation method of a cationic cholesterol derivative containing a natural cholesterol skeleton and a lysine head group, in particular to a synthesis method of a cationic cholesterol derivative containing a natural cholesterol skeleton and a lysine head group, a preparation method of a nano-composite and an application of the nano-composite serving as an efficient gene vector to a small interfering RNA (siRNA) and microRNA transfection reagent. According to the cationic cholesterol derivative containing the natural cholesterol skeleton and the lysine head group provided by the invention, the Linker chain length most suitable for siRNA combination is selected, and the nano-composite provided by the invention preferably adopts a micro-fluidic technology to systematically optimize various parameters (including total flow velocity, flow velocity ratio, buffer system, chip structure and the like), so that the stability of the nano-composite is improved, and the stability of the nano-composite is improved. A stable nano compound is formed, and efficient gene delivery capability can be realized without auxiliary lipid.

The invention discloses a drug-loaded nano-micelle with multiple drug release functions and a preparation method of the drug-loaded nano-micelle. The preparation method comprises the following steps that: firstly, carboxylation modified beta-CD is chemically grafted onto a PEG molecular chain to prepare a CD-PEG monomer; then, a cholesterol derivative is grafted to a molecular chain of the CD-PEG, and a Chol-PEG-CD ternary monomer is prepared; an ultrasonic emulsification-solvent evaporation method is adopted, and an anti-cancer drug is entrapped in the Chol-PEG-CD molecule self-assembly process, so that a drug-loaded nano-micelle is prepared. The drug-loaded micelle prepared by the invention has a multi-stage drug release function which is characterized in that the drug-loaded micelle is firstly suddenly released for rapid drug delivery and then slowly released for continuous drug delivery. The drug-loaded nano-micelle can deliver a drug to a focus site in a targeted manner through an EPR effect, so that the toxic and side effects of the drug are reduced. The drug-loaded nano-micelle with multiple drug release functions prepared by the invention has application advantages in the aspects of targeted delivery of anti-cancer drugs and tumor treatment.

A lipid derivative in which a hydrophilic polymer is bound through a cyclic benzylidene acetal linker, and which can accurately control a hydrolysis rate in the weakly acidic environment of a living body to detach the hydrophilic polymer from a lipid membrane structure. The lipid derivative is represented by formula (1):wherein, R1 and R6 are each independently a hydrogen atom or a hydrocarbon group; R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; R7 is a hydrocarbon group having from 8 to 24 carbon atoms, an acyl group having from 8 to 24 carbon atoms, a cholesterol derivative, a glycerolipid, a phospholipid or a sphingolipid; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; and Z1 and Z2 are each independently a selected divalent spacer.

The invention specifically relates to a chloroquine cholesterol derivative, and a preparation method and application thereof, belonging to the field of the chemical pharmaceutical industry. The chloroquine cholesterol derivative provided by invention has a structure as shown in a formula I which is described in the specification. The invention also provides the preparation method and application of the chloroquine cholesterol derivative. The chloroquine cholesterol derivative provided by the invention can effectively inhibit the proliferation of rat fibroblasts and treat pulmonary fibrosis, exerts anti-inflammatory effect, and offers a novel option for preparation of anti-fibrotic, anti-inflammatory and anti-tumor drugs.

The present invention discloses a preparation method of gel emulsion and low-density fluorescent porous metal complex material prepared by templating gel emulsion. The preparation method comprises the following steps: mixing a solution formed by dissolving an aromatic carboxylic acid type cholesterol derivative serving as an organic ligand in an oil phase with a solution formed by dissolving metal salts such as terbium nitrate and europium nitrate in a water phase; and using a complex formed by an in-situ self-assembly reaction of an organic ligand and metal ions on an oil-water interface as a stabilizer to obtain a W / O type gel emulsion, wherein the gel emulsion has reversible damage-recovery thixotropic performance. When an oil phase is a polymerizable monomer (such as styrene), the gel emulsion can be used as a template, a low-density fluorescent porous metal complex material is prepared through initiation polymerization of the oil phase, the material can be dried at room temperature, some high-energy-consumption means such as supercritical drying, freeze drying and the like and large professional equipment are not needed, and the material has the characteristics of simple preparation, excellent material performance, convenient processing and the like, and is easy to realize large-scale industrial production.

The invention belongs to the field of display technology, and in particular relates to a frame sealing glue, a packaging method of a display panel and a display panel. The frame sealant includes a frame sealant matrix, and also includes a siloxane side chain type liquid crystal elastomer. The linking agent is formed through a hydrosilylation reaction, wherein the liquid crystal monomer is a cholesterol derivative, and the crosslinking agent is a binaphthyl diol derivative. The frame sealant can effectively slow down or prevent liquid crystals from being polluted by small molecules in the frame sealant during the boxing process of the array substrate and the color filter substrate, reduce the impact force of the liquid crystal on the frame sealant, and improve the quality of the liquid crystal display panel.

The invention discloses a cholesterol derivative, an O / W / O multi-phase gel emulsion prepared from the cholesterol derivative, and a method for preparing a porous silicon dioxide bulk material from the emulsion. The structural formula of the cholesterol derivative is as shown in the description, wherein n is an integer of 6 to 12, and R represents a C1-C4 alkyl group. The O / W / O multi-phase gel emulsion is prepared according to a one-step method by taking the cholesterol derivative as a sing surfactant and taking a silanization reagent as an oil-phase material, and is high in stability, stable to acid and alkali, uniform in droplet distribution, and high in water-phase content which is 80 to 97 percent of the total volume. The porous silicon dioxide bulk material is prepared by taking the O / W / O multi-phase gel emulsion as a template at an ammonia gas atmosphere. The method is simple and low in cost; the prepared silicon dioxide bulk material is low in density, and has rich hierarchical porous structures which are regular and high in permeability; moreover, the porous silicon dioxide bulk material is large in surface area, high in heat stability, adjustable in hydrophilicity and hydrophobicity, and excellent in water or oil adsorption property.

The invention discloses a cholesterol derivative with 19-bit methyl oxidized into carboxyl, and a preparation method and application thereof; during preparation, bud-dichasial junceella juncea is firstly extracted by alcohol; the extract is decompressed and concentrated to obtain an extractum; the extractum suspends in water and then extracted by an organic solvent to obtain extract liquid; afterbeing decompressed and concentrated, the extract liquid is separated by chromatography of silicagel columns, gel chromatography and high-performance liquid phase chromatography to obtain the cholesterol derivative with 19-bit methyl oxidized into the carboxyl. The cholesterol derivative with 19-bit methyl oxidized into the carboxyl and derived from the bud-dichasial junceella juncea has stronger insecticidal activity and can be used for developing biological agricultural chemicals, thus having broad application prospect.

The invention discloses a styrene volatilization inhibitor based on a cholesterol derivative, and a preparation method thereof, wherein the styrene volatilization inhibitor comprises, by weight, 20-70parts of a cholesterol derivative, 0-5 parts of paraffin, and 30-80 parts of a diluent. The preparation method comprises: uniformly mixing a cholesterol derivative, paraffin and a diluent, and filtering. According to the present invention, the styrene volatilization inhibitor constructed based on the cholesterol derivative is added to a unsaturated resin, and the styrene volatilization inhibitorcan float on the surface and form a film during the resin standing and curing, such that the volatilization rate of styrene can be significantly reduced while the interlayer adhesion of the unsaturated resin product cannot be affected, the good leveling property can be achieved, the appearance of the product cannot be affected, and the weather resistance is good.