30 results about "Hydroxycholesterols" patented technology

Methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof are provided. The methods involve providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to the subject e.g. by 1) administering 25HC3S to the subject; or 2) overexpressing, in the subject, the hydroxysterol sulfotransferase enzyme SULT2B1b, which catalyzes the sulfation of 25-hydroxycholesterol (25HC) to form 25HC3S.

The invention discloses a production method of 25-hydroxycholesterol. The production method comprises the following steps: 1) protecting 3-hydroxyl of 24-dehydrocholesterol to obtain acylated 24-dehydrocholesterol; 2) reacting the acylated 24-dehydrocholesterol with deionized water and a halogenating reagent in a solvent at a temperature ranging from -20 DEG C to -1 DEG C for 2-4 hours to obtain a hydroxyhalogenated product; and 3) reacting the hydroxyhalogenated product with hydrogen in an organic solvent under the catalysis of an alkali and a Lindlar catalyst to obtain the 25-hydroxycholesterol. The production method of the 25-hydroxycholesterol, which is disclosed by the invention, is relatively mild in conditions, relatively short in reaction time and reliable in results because the Lindlar catalyst is used for reaction; as the hydrogen is used as a hydrogen source, the production cost of the production method is reduced and the production method is green and clean.

The present invention provides a cyclic cholane carboxylate derivative and a preparation method thereof, and uses of the cyclic cholane carboxylate derivative in industrial preparation of 25-hydroxycholesterol (1), wherein R1 in the cyclic cholane carboxylate derivative represented by a formula I is straight chain or branched chain C1-C12 alkyl, R2 is methyl or ethyl, and the formula (I) is defined in the specification. According to the present invention, the starting raw material stigmasterol of the 25-hydroxycholesterol (1) synthesis process route has characteristics of low price, easy obtaining and reliable commercial source; and particularly during the constructing of the 17-position side chain of 25-hydroxycholesterol (1), the reaction conditions are mild, the reaction steps are simple, the special and dangerous reagents are not required, the harsh reaction conditions are not required, the redundant reaction steps are not required, the chromatographic separation and purification is not required, the industrial production is easily achieved, and the significant progress is achieved compared to the prior art.

The invention discloses a synthetic method of 25-hydroxycholesterol. The synthetic method comprises the following steps: (1) protecting 3-hydroxy of 24-dehydrocholesterol so as to obtain acylated 24-dehydrocholesterol; (2) carrying out epoxidation reaction on double bonds on the 24th site of the product obtained in the step (1), namely carrying out epoxidation reaction on the acylated 24-dehydrocholesterol and an epoxidation reagent in a solvent II under the catalytic action of manganese salt so as to obtain an epoxidation product; and (3) carrying out reduction ring opening on the epoxidation product obtained in the step (2), namely carrying out reduction ring opening on the epoxidation product obtained in the step (2) and a reduction reagent in a solvent III so as to obtain the 25-hydroxycholesterol. The synthetic method of the 25-hydroxycholesterol has the advantages that peroxyacetic acid and meta-chloroperoxybenzoic acid which are non-toxic and low in cost are used as the epoxidation reagents and environmentally-friendly, the reaction is carried out at a low temperature, and the manganese salt is used as a catalyst and is high in selectivity.

The invention relates to the field of chemical drugs, and discloses an application of 25-hydroxycholesterol in inhibiting flaviviruses. Specifically, the invention discloses an application of the 25HC (25-hydroxycholesterol) in preparing medicines for preventing and / or treating flavivirus infection, in inhibiting the flaviviruses and in preparing medicines for preventing and / or treating microcephaly caused by Zika virus infection. The invention also discloses a pharmaceutical composition, wherein the pharmaceutical composition consists of the 25HC, at least one adjuvant agent conductive to inhibition of the flaviviruses and at least one pharmaceutically acceptable vector. With the application of the 25HC, the flaviviruses can be inhibited, so that a protecting effect is taken on a host; and specifically, the 25HC can be used for inhibiting the flavivirus infection in human cell, mouse and rhesus monkey models, and can be used for preventing and / or treating the microcephaly caused by Zika viruses.

A rapid test kit for detecting adulterate reconstituted milk mixed in fresh and raw milk is characterized in that the kit comprises the following components: 1) a series of standard products of a cholesterol oxidation product; 2) an elisa plate coated with a coating antigen; 3) a specific conjugate solution; 4) an enzyme marker solution; 5) a chromogenic substrate; 6) a stop solution and 7) a wash concentrate; wherein the cholesterol oxidation product is any one of 7-keto-cholesterol, 7-alpha-hydroxycholesterol and 25-alpha-hydroxycholesterol; the coating antigen is a coating antigen obtained by coupling any one of the 7-keto-cholesterol, the 7-alpha-hydroxycholesterol and the 25-alpha-hydroxycholesterol with a carrier protein; a specific conjugate is a corresponding monoclonal or polyclonal antibody of one of the 7-keto-cholesterol, the 7-alpha-hydroxycholesterol and the 25-alpha-hydroxycholesterol, or a protein, capable of specifically binding with one of the 7-keto-cholesterol, the 7-alpha-hydroxycholesterol and the 25-alpha-hydroxycholesterol, such as cholesterol oxide and derivative binding protein (OBP, oxysterol binding protein). The rapid test kit aiming at the current complex situation of dairy product quality supervision can play a significant role in grass-roots inspection and government regulation.

The invention provides a drug for inhibiting intra-cellular replication in porcine reproductive and respiratory syndrome virus (PRRSV). Through cellular-level research on the effect of 25-hydroxycholesterol (25HC) on the PRRSV, the result shows that the 25HC can obviously inhibit replication of multiple strains of the PRRSV, adsorption and entry phases of replication cycles of the PRRSV can be inhibited without affecting synthesis of viral genomes and release of virus particles, and the 25HC does not have a direct inactivation function on the virus particles of the PRRSV. The 25HV is hopefully developed into a candidate drug for preventing the PRRSV. The new drug is provided for preventing and treating the PRRSV, and good market value and clinical prospect are achieved.

The present invention relates to a synthesis method for 25-hydroxy-7-ketocholesterol. The method comprises: using a 25-hydroxycholesterol derivative as a raw material in an organic solvent, initiating by an initiator in the presence of an N-hydroxy catalyst; reacting 1-40 hours at a temperature of 0 DEG C-150 DEG C with air or oxygen; performing dehydration reaction for 1-20 hours by adding a dehydrant at a temperature of -20 DEG C-100 DEG C after completion of the reaction; then performing hydrolysis reaction for 1-2 hours at a temperature of 50 DEG C-80 DEG C; and obtaining 25-hydroxy-7-ketocholesterol after separation treatment of the reaction solution. The raw materials and reagents used in the present invention are readily available and environmentally-friendly. The synthesis method for 25-hydroxy-7-ketocholesterol provided by the present invention avoids the use of the metal Cr, the oxidant PCC and the like that pollute the environment seriously, and is good in reaction sclectivity, high in yield, low in cost, simple in treatment thereafter, less in three wastes, easy in product separation and high in purity.

This invention relates, e.g., to a method for inhibiting the growth and / or proliferation and / or infectivity of a virus in a cell, such as a mammalian cell (e.g. for inhibiting entry of the virus into the cell), comprising administering, or causing to be administered, to the cell, 25-hydroxycholesterol (25HC) in an amount sufficient to inhibit the growth and / or proliferation and / or infectivity of the virus in the cell. The method can be carried out in vivo or in vitro. Among the viruses that can be inhibited are, e.g., VSV, HSV, MHV68, HCV, HIV, EBOV, RVFV, RSSEV and Nipah virus. In one embodiment of the invention, the 25HC is administered topically, e.g. to a mucosal surface.

Disclosed is a method for detection of 24S-hydroxycholesterol in hair. More specifically, a trace amount of hair is hydrolyzed under basic condition and metabolites including 24S-hydroxycholesterol are purified and extracted by solid-phase extraction (SPE). Then, after derivatization of the resulting extract with trimethylsilyl (TMS), 24S-hydroxycholesterol is detected by gas chromatography-mass spectrometry (GC-MS).

PCT No. PCT / JP96 / 02369 Sec. 371 Date Feb. 26, 1998 Sec. 102(e) Date Feb. 26, 1998 PCT Filed Aug. 26, 1996 PCT Pub. No. WO97 / 08336 PCT Pub. Date Mar. 6, 1997A method for preparing at least one hydroxycholesterol chosen from the group consisting of 25-hydroxycholesterol, 17,25-dihydroxycholesterol and 25,26-dihydroxycholesterol by biological hydroxylation of cholesterol, and the aforementioned dihydroxycholesterols. In the above biological hydroxylation, a microorganism is used which has the abovementioned hydroxylation capacity and which belongs to the genus Amycolata and the genus Sphingomonas.

The invention discovers that 25-hydroxycholesterol is capable of effectively inhibiting copy of a 71-type enterovirus and a 68-type enterovirus. The invention provides 25-hydroxycholesterol or pharmaceutically acceptable salt or ester or use of 25-hydroxycholesterol in preparation of a drug for preventing and / or treating diseases and / or symptoms caused by the infection of enteroviruses and further provides an administration route and dose form applicable to the drug, other active components containable in the drug and combined medication of the drug and other drugs. Besides, the invention further provides a non-therapeutic purpose method for inhibiting the enteroviruses in cells by virtue of 25-hydroxycholesterol or pharmaceutically acceptable salt or ester.

The invention discloses a production method of 25-hydroxycholesterol. The production method comprises the following steps: 1) protecting 3-hydroxyl of 24-dehydrocholesterol to obtain acylated 24-dehydrocholesterol; 2) reacting the acylated 24-dehydrocholesterol with deionized water and a halogenating reagent in a solvent at a temperature ranging from -20 DEG C to -1 DEG C for 2-4 hours to obtain a hydroxyhalogenated product; and 3) reacting the hydroxyhalogenated product with hydrogen in an organic solvent under the catalysis of an alkali and a Lindlar catalyst to obtain the 25-hydroxycholesterol. The production method of the 25-hydroxycholesterol, which is disclosed by the invention, is relatively mild in conditions, relatively short in reaction time and reliable in results because the Lindlar catalyst is used for reaction; as the hydrogen is used as a hydrogen source, the production cost of the production method is reduced and the production method is green and clean.

The present invention discloses a method for synthesizing 25-hydroxy cholesterol. The method is as below: subjecting 24-dehydrocholesterol derivative as a raw material, which undergoes an addition reaction with a hydroxyl containing reagent in an organic solvent under catalysis, and then hydrolyzing the reaction product and separating to obtain 25-hydroxy cholesterol. The present invention adopts hydroxyl containing reagents such as water, formic acid, acetic acid, propionic acid, butyric acid, benzoic acid, p-methyl benzoic acid to replace the commonly used extremely toxic reagents such as Cr reagent, Hg reagent and polyfluorinated acetone in the prior art. The raw materials of the present invention are easily available, and have low effect on environment. The operation and post treatment are convenient. Moreover, the method has the advantages of mild reaction conditions, simple operation, good selectivity, high efficiency, high yield, simple post treatment, easy product separation, less three wastes and easy industrialization.

Disclosed are methods for determining efficacy of a cyclodextrin therapy in a subject afflicted with a disorder involving oxysterol accumulation. These methods comprise: obtaining a first body fluid sample from the subject prior to cyclodextrin administration; administering cyclodextrin; obtaining at least one second body fluid sample after the cyclodextrin administration; subjecting the body fluid samples to chromatography-mass spectroscopy analysis to determine concentration of 24-hydroxycholesterol and / or cholestane-3β,5α,6β-triol; and determining magnitude of difference between the 24-hydroxycholesterol and / or cholestane-3β,5α,6β-triol concentration of the body fluid samples, whereby an increase or stabilization of 24-hydroxycholesterol concentration, or a reduction of cholestane-3β,5α,6β-triol concentration in the at least one second sample compared to the first sample, indicates efficacy of the cyclodextrin therapy.

The present invention relates to a method for in vitro maturation of oocytes comprising the steps of:(a) culturing one or more GV oocytes in a culture medium, the culture medium comprising a nuclear maturation inhibiting substance and comprising one or more gonadotropins and / or one or more growth factors, the culturing taking place for a time period sufficient for cytoplasmatic maturation to occur;(b) washing the GV oocytes of step (a) to remove the nuclear maturation inhibiting substance;(c) culturing the washed oocytes of step (b) in a culture medium comprising one or more gonadotropins and / or one or more growth factors and / or MAS for a time period sufficient for nuclear maturation.The invention also relates to an oocyte culture medium comprising a nuclear maturation inhibiting substance and comprising one or more gonadotropins and / or one or more growth factors. The nuclear maturation inhibiting substance may be a MAS antagonist or an FF-MAS synthesis inhibitor, preferably a cytochrome P450 lanosterol 14α-demethylase (P45014DM) inhibitor e.g. ketoconazole or 22-hydroxycholesterol. The one or more gonadotropins and / or one or more growth factors are preferably a combination of EGF and FSH and / or LH.The invention also relates to the use of a nuclear maturation inhibiting substance and one or more gonadotropins and / or one or more growth factors as described above for the preparation of a cell culture medium for in vitro maturation of oocytes.

The present invention relates to a pharmaceutical composition comprising (a) 7β-hydroxycholesterol, (b) a water soluble organic solvent, preferably propylene glycol and / or DMSO, and (c) a solubilizing agent, preferably PEG hydrated castor oil, and to a method for preparing the same. This composition is suitable for preparing an intravenously administered preparation and comprises the pharmaceutically active substance β-hydroxycholesterol, which is poorly soluble in water.

The invention relates to an application of 22 (R)-hydroxycholesterol as 1-type poly (ADP-ribose) synthetase inhibitor. 22 (R)-hydroxycholesterol as a cholesterol analogue does not have the cytotoxic effects of common anti-tumor drugs or other 1-type poly (ADP-ribose) synthetase inhibitors, and the safety of the 22 (R)-hydroxycholesterol can be predicated. The 22 (R)-hydroxycholesterol can be widely applied as the medicine for treating cholesterol related diseases, including cardiovascular diseases, tumour and the like.

The invention discloses the application of 25-hydroxycholesterol in promoting the proliferation of chicken primordial germ cells. The inventor has studied in depth the impact of 25-hydroxycholesterol on the proliferation of chicken primordial germ cells. The results showed that adding 25‑hydroxycholesterol to the existing culture medium of chicken primordial germ cells could promote the proliferation of chicken primordial germ cells. According to the difference of adding 25-hydroxycholesterol concentration, its promotion degree to chicken primordial germ cell proliferation is different, and when 25-hydroxycholesterol concentration is 1 μ M, its action effect is the most remarkable, can effectively promote chicken primordial germ cell proliferation in vitro Proliferate, and chicken primordial germ cells can well maintain their biological characteristics in the culture medium containing this concentration of 25-hydroxycholesterol.

The present disclosure provides compositions comprising 25-hydroxycholesterol, derivatives and prodrugs thereof, and methods of use thereof. Specifically, disclosed herein are methods of decreasing neuronal cell death.

The invention relates to an application of 22 (R)-hydroxycholesterol as 1-type poly (ADP-ribose) synthetase inhibitor. 22 (R)-hydroxycholesterol as a cholesterol analogue does not have the cytotoxic effects of common anti-tumor drugs or other 1-type poly (ADP-ribose) synthetase inhibitors, and the safety of the 22 (R)-hydroxycholesterol can be predicated. The 22 (R)-hydroxycholesterol can be widely applied as the medicine for treating cholesterol related diseases, including cardiovascular diseases, tumour and the like.

This invention relates, e.g., to a method for inhibiting the growth and / or proliferation and / or infectivity of a virus in a cell, such as a mammalian cell (e.g. for inhibiting entry of the virus into the cell), comprising administering, or causing to be administered, to the cell, 25-hydroxycholesterol (25HC) in an amount sufficient to inhibit the growth and / or proliferation and / or infectivity of the vines in the cell. The method can be carried out in vivo or in vitro. Among the viruses that can be inhibited are, e.g., VSV, HSV, MHV68, HCV, HIV, EBOV, RVFV, RSSEV and Nipah virus. In one embodiment of the invention, the 25HC is administered topically, e.g. to a mucosal surface.

The invention discloses a 20-hydroxycholesterol-Biotin molecular probe and a preparation method and application thereof. 20-hydroxycholesterol is used as a raw material and performs condensation reaction with Biotin-OSu to obtain the 20-hydroxycholesterol-Biotin molecular probe shown as a formula (1). The preparation method has the advantages of mild reaction conditions, simple and easy operation and high yield. The invention further discloses application of the 20-hydroxycholesterol-Biotin molecular probe in identification of 20-hydroxycholesterol binding proteins.

A method for preparing at least one hydroxycholesterol chosen from the group consisting of 25-hydroxycholesterol, 17,25-dihydroxycholesterol and 25,26-dihydroxycholesterol by biological hydroxylation of cholesterol, and the aforementioned dihydroxycholesterols. In the above biological hydroxylation, a microorganism is used which has the abovementioned hydroxylation capacity and which belongs to the genus Amycolata and the genus Sphingomonas.

The invention discloses a synthetic method of 25-hydroxycholesterol. The synthetic method comprises the following steps: (1) protecting 3-hydroxy of 24-dehydrocholesterol so as to obtain acylated 24-dehydrocholesterol; (2) carrying out epoxidation reaction on double bonds on the 24th site of the product obtained in the step (1), namely carrying out epoxidation reaction on the acylated 24-dehydrocholesterol and an epoxidation reagent in a solvent II under the catalytic action of manganese salt so as to obtain an epoxidation product; and (3) carrying out reduction ring opening on the epoxidation product obtained in the step (2), namely carrying out reduction ring opening on the epoxidation product obtained in the step (2) and a reduction reagent in a solvent III so as to obtain the 25-hydroxycholesterol. The synthetic method of the 25-hydroxycholesterol has the advantages that peroxyacetic acid and meta-chloroperoxybenzoic acid which are non-toxic and low in cost are used as the epoxidation reagents and environmentally-friendly, the reaction is carried out at a low temperature, and the manganese salt is used as a catalyst and is high in selectivity.