68 results about "Hydroxyprogesterone" patented technology

The invention relates to 17-HPC pulmonary formulations for administration by inhalation comprising 17-HPC and a pharmaceutically acceptable excipient. Particle size reduction of 17-HPC is required for the pulmonary delivery, and can be achieved with a surfactant or water without the surfactant. Preferred pulmonary formulations include a powder blend comprising a therapeutically effective amount of at least one steroid hormone (progestogen) as a glucocorticoid sensitizer, and at least one pharmaceutically acceptable excipient, wherein the at least one steroid hormone (progestogen) has a particle size distribution profile ranging from about one nanometer to about ten microns in the powder blend.

The invention provides a method for simultaneously detecting 13 kinds of steroid hormones in serum. The method includes the following steps: a to-be-tested serum sample is mixed with an internal standard solution, a detection liquid is obtained by liquid-liquid extraction, and detection is performed by ultra-high-performance liquid chromatography-tandem mass spectrometry; liquid chromatography conditions are that: a mobile phase A is a formic acid aqueous solution of 0.1%, and a mobile phase B is a formic acid methanol solution of 0.1%; mass spectrometry conditions are that: a positive ion mode employs a multi-reaction monitoring mass spectrometry scanning mode; and the 13 kinds of steroid hormones include pregnenolone, progesterone, 17-hydroxypregnenolone, 17[alpha]-hydroxyprogesterone, 11[alpha]-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycorticosterone, corticosterone, cortisol, 11-deoxycortisol, cortisone, aldosterone, and estrone. The method simultaneously detects the 13 kindsof steroid hormones with the detection time of only 6 minutes, and is easy to operate and takes less time; the sensitivity is high, the accuracy is good, the specificity is strong, a detection range is wide, and an application prospect in medical and biochemical detection fields is broad.

The present invention provides for bioavailable oral dosage forms containing esters of 17-hydroxyprogesterone as well as related methods. The oral dosage forms can be formulated for pregnancy support and can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. In another embodiment, a pharmaceutically acceptable oral dosage form for pregnancy support is provided. The pharmaceutically acceptable oral dosage can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. The oral dosage form can, when measured using a USP Type-II dissolution apparatus in 900 mL of deionized water with 0.5 (w / v) of sodium lauryl sulfate at 50 RPM at 37° C., release at least 20 wt % of the dose of the ester of 17-hydroxyprogesterone after 60 minutes, or in the alternative release at least 20 wt % more after 60 minutes than an equivalently dosed oral dosage form without the carrier.

The invention discloses a synthesis method of medroxyprogesterone acetate. The method comprises the following steps of: 1) enabling 17 alpha-hydroxyprogesterone and ethylene glycol to perform ketalation under the catalysis of para-toluenesulfonic acid to obtain a ketal; 2) enabling the ketal to perform epoxidation reaction under the action of a peroxyacetic acid solution of anhydrous sodium acetate to obtain an epoxide; 3) enabling the epoxide and methylmagnesium bromide to perform Grignard reaction, and then performing hydrolysis reaction by dilute sulphuric acid to obtain a Grignard matter; 4) performing hydrolysis on the Grignard matter by glacial acetic acid to perform deprotection so as to obtain 5 alpha, 17 alpha-dihydroxy-6 beta-methyl progesterone; 5) performing hydrogenation translocation reaction under the action of hydrogen chloride to obtain 6 alpha-methyl-17 alpha-hydroxyprogesterone; and 6) enabling the 6 alpha-methyl-17 alpha-hydroxyprogesterone to perform acetylation reaction with acetic acid and acetic anhydride so as to obtain the medroxyprogesterone acetate. During the reaction process of the method disclosed by the invention, the use of a precious metal catalyst, namely palladium on carbon is avoided, the cost of auxiliary materials and the recovery cost are greatly reduced, the reaction conditions in each step are mild, the violent heat release and deflation phenomena are avoided, and the safety in production is good.

The invention discloses a method and kit for detecting amino acid, carnitine, ketone and hormone at the same time. The method comprises the following steps: incubating a to-be-detected blood spot sample by using an extracting working liquid; and centrifuging, taking supernatant and detecting the supernatant by using tandem mass spectrum to acquire amino acid, carnitine, ketone and hormone information, wherein the extracting working liquid comprises an amino acid isotope internal standard product, a carnitine isotope internal standard product, a 17alpha hydroxyprogesterone isotope internal standard product, a succinyl acetone isotope internal standard product and an organic solvent. By the method provided by the invention, the four substances such as amino acid, carnitine, ketone and hormone can be detected simultaneously only by one-time blood collection, so that the labor cost is reduced and the influence on the body and mind of a to-be-detected person by multi-time blood collection is avoided. By the method, 13 kinds of amino acid, 32 kinds of carnitine, 1 kind of hormone and 1 kind of ketone are detected quantitatively at a time, 46 inherited metabolic diseases can be screened according to the indexes, and the screening efficiency of the inherited metabolic diseases of newborns is improved.

The invention relates to a method for preparing 17alpha-hydroxyprogesterone. The17alpha-hydroxyprogesterone is prepared by taking 17beta- cyano-5-androstene-17-ol-3,3-diethylene ketal (referred as an intermediate II) as a raw material and dimethylzinc or methylzinc chloride as a reagent; the content of the 17alpha-hydroxyprogesterone by HPLC is above 99.5% and the weight yield is 83-87%. The method comprises the following steps of dissolving the intermediate II in an organic solvent, adding lithium chloride as a catalyst, stirring, raising the temperature to 40-80 DEG C, dropwise adding a toluene solution of dimethylzinc or methylzinc chloride of which the concentration is 2M, and continuing to complete the reaction; and then adding an ammonium chloride solution of which the concentration is 25% to destruct an organic zinc reagent, separating the aqueous layer out and extracting, merging the organic layer and the extract and concentrating the solvent to near dryness, and then adding lower alcohol, stirring, raising the temperature to 40-60 DEG C, adding the acid of which the concentration is 2M, hydrolyzing, adjusting the pH value with a weak base after the reaction is completed, evaporating 90% of the solvent out, adding tap water, cooling and crystallizing to obtain a crude 17alpha-hydroxyprogesterone product; and then carrying out reflux decolorizing on the crude product with activated carbon by virtue of alcohol, and refining to obtain the commercial grade 17alpha-hydroxyprogesterone. The 17alpha-hydroxyprogesterone produced by the method disclosed by the invention has the advantages of good purity and high yield and is economic and environment-friendly, and the solvent can be recycled.

A slow-releasing oxytocic for artificially inducing the maturation of epinephelus' sex gland and the ovulation or ejaculation by embedding it in body of epinephelus is prepared from luliberin like, 17 alpha-hydroxyprogesterone, cholesterin, cellulose and plant oil through proportional mixing and moulding.

Provided is a preparation method for 17a-hydroxyprogesterone or analogs thereof, comprising the following steps: the compound as represented in formula (4) reacts in solvent and trihalomethane in the presence of magnesium metal and lithium halide; hydrolysis is carried out using acidic substance; the target product (1) is collected from the reaction product. The present invention lowers production cost and prevents problems such as environment polluting byproducts and highly toxic, unstable reagents and intermediate products. The reaction conditions are moderate, and the purity after simple purifications can exceed 99%. The present invention is easy to implement in industry. The reaction formula is as (4), (1).

The invention relates to a method for detecting steroid hormones in blood. The method comprises the following steps: preparation of a standard curve dried blood spot sample: preparing red blood cells by using whole blood; by taking hormone-removed serum as a blank matrix, adding standard substances such as 17alpha-hydroxyprogesterone, androstenedione, cortisol, 21-deoxycortisol and 11-deoxycortisol solutions to prepare a series of serum standard curve working solutions; mixing the red blood cells with the serum standard curve working solution, and preparing a standard curve dried blood spot sample by using the obtained mixed solution; pretreatment of the dried blood spot sample: taking the dried blood spot sample, adding an internal standard-containing extraction liquid, extracting, centrifuging, drying, adding a reconstitution fluid, centrifuging, and determining by adopting liquid chromatography-tandem mass spectrometry. The detection method disclosed by the invention is simple in pretreatment operation, short in time consumption, high in stability and good in reproducibility, and various steroid isomers can be efficiently separated at the same time.

An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting a of: the conversion of cholesterol to pregnenolone; the conversion of pregnenolone to progesterone; the conversion of progesterone to 17alpha-hydroxy-progesterone; the conversion of 17alpha-hydroxyprogesterone to cortexolone; the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host.

The invention provides a method for synthesizing 17alpha-hydroxyprogesterone.17beta-cyano-5-androstene-17-alcohol-3,3-ethylene dihydroxy ketal (an intermediate II for short) is adopted as a raw material, and cheap cyclohexanone cyanohydrin is adopted as an inhibitor of a main impurity methyltestosterone. Due to the fact that a cyclohexanone cyanohydrin structure is similar to a D-loop structure in the molecular structural formula of the intermediate II and can replace a D loop to react with OH<1> in a Grignard reaction system, generated methyltestosterone is greatly reduced. Under the catalytic action of anhydrous lithium chloride or CuCl, the reaction temperature is reduced to -15 DEG C to -10 DEG C, and other generated impurities can be reduced at the low temperature. Therefore, the product quality is improved by controlling Grignard reaction conditions, the content of crude HPLC can reach 98% or above, and the total weight yield ranges from 84% to 88% and is improved by 10% to 14% compared with a traditional process.

The invention relates to the technical field of preparation of diene ketal, and particularly discloses a preparation method of a dydrogesterone intermediate diene ketal. 7alpha-hydroxyprogesterone isinvolved; the preparation method comprises the steps that 1, the 7alpha-hydroxyprogesterone is taken and put into a glass beaker; 2, an organic solvent is added to the glass beaker, and the glass beaker is subjected to water bath heating; 3, an acid catalyst is added to the glass beaker in step 2, and water bath heating continues; 4, a placement reaction is carried out, the reaction time is 4-8 hours, and therefore ketal can be obtained; 5, a certain quantity of a reaction solvent is added in the ketal obtained in step 4, and concentration and purification are carried out to obtain the diene ketal. The preparation method of the dydrogesterone intermediate diene ketal has the advantages that the 7alpha-hydroxyprogesterone can be subjected to a ketal reaction and a dehydroxylation reaction to quickly prepare the diene ketal, and the preparation method is simple, efficient, suitable for industrialized production and convenient to use by people.

The present invention provides for bioavailable oral dosage forms containing esters of 17-hydroxyprogesterone as well as related methods. The oral dosage forms can be formulated for pregnancy support and can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. In another embodiment, a pharmaceutically acceptable oral dosage form for pregnancy support is provided. The pharmaceutically acceptable oral dosage can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. The oral dosage form can, when measured using a USP Type-II dissolution apparatus in 900 mL of deionized water with 0.5 (w / v) of sodium lauryl sulfate at 50 RPM at 37° C., release at least 20 wt % of the dose of the ester of 17-hydroxyprogesterone after 60 minutes, or in the alternative release at least 20 wt % more after 60 minutes than an equivalently dosed oral dosage form without the carrier.

The present invention discloses chemical synthesis of free megestrol. The initial material 17alpha-hydroxyprogesterone is first methenylated to form methenylated substance, the methenylated substance is then mixed with Pd / C catalyst, dimethylformamide and cyclohexene and reacted at 50-70 deg.c for 1-3 hr, and the product is post-treated to obtain free megestrol. The improved synthesis process of the present invention has complete methylation, less side product, high product purity, high quality stability, high yield and low production cost, and may be used in industrial production.

The invention discloses a method for preparing 11Alpha,17Alpha-hydroxyprogesterone, comprising: using 17Alpha-hydroxyprogesterone as a substrate, adding magnetic nano ferroferric oxide powder into a culture medium, and preparing 11Alpha,17Alpha-hydroxyprogesterone by Aspergillus ochraceus fermentation process; the method has the advantages that feeding concentration is high, substrate molar conversion rate is high, the feeding concentration is up to 30 g / L, and the highest molar conversion ratio is up to 91.9%; the magnetic nano ferroferric oxide powder is recyclable; by using the magnetic nano ferroferric oxide powder, it is possible to greatly increase hydroxyl conversion rate, the process is simple, the production cost is simple, and the method has great industrial application prospect.

The present invention provides for bioavailable oral dosage forms containing esters of 17-hydroxyprogesterone as well as related methods. The oral dosage forms can be formulated for pregnancy support and can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. In another embodiment, a pharmaceutically acceptable oral dosage form for pregnancy support is provided. The pharmaceutically acceptable oral dosage can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. The oral dosage form can, when measured using a USP Type-II dissolution apparatus in 900 mL of deionized water with 0.5 (w / v) of sodium lauryl sulfate at 50 RPM at 37° C., release at least 20 wt % of the dose of the ester of 17-hydroxyprogesterone after 60 minutes, or in the alternative release at least 20 wt % more after 60 minutes than an equivalently dosed oral dosage form without the carrier.

The invention discloses a steroid hormone detection method that comprises the following steps: adding an internal standard substance into a sample to be detected; carrying out a derivatization reaction; detecting an analyte by using chromatography tandem mass spectrometry; the analyte comprises a first steroid hormone and a second steroid hormone at the same time; the first steroid hormone is selected from at least one of the following steroid hormones: estradiol and estriol; and the second steroid hormone is selected from at least one of the following steroid hormones: dehydroepiandrosterone,dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, androstenedione, cortisol, cortisone, 11-deoxycortisol, 17alpha-hydroxyprogesterone, 17alpha-hydroxypregnenolone, aldosterone, cortisol, deoxycortisol, progesterone and pregnenolone. The detecting method has the advantages of few operation steps and short detection time, and can specifically, sensitively, accurately and quantitatively analyze the analyte substance.

An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins of catalyzing an oxidation step in the biological pathway, for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of:< / PTEXT>the conversion of cholesterol to pregnenolone;< / PTEXT>the conversion of pregnenolone to progesterone;< / PTEXT>the conversion of progesterone to 17alpha-hydroxyprogesterone;< / PTEXT>the conversion of 17alpha-hydroxyprogesterone to cortexolone;< / PTEXT>the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in that host.< / PTEXT>

The invention discloses a novel preparation method of 6-methyl-17 alpha-hydroxyprogesterone and a precursor 6-methylene-17-alpha-hydroxyprogesterone thereof. The 6-methylene-17-alpha-hydroxyprogesterone is prepared through a hydroformylation reaction via CO / H2 under the conditions that 17-alpha-hydroxyprogesterone is used as a raw material and a rhodium-loaded molecular sieve is used as a catalyst, and conducting reducing by using potassium borohydride. The 6-methyl-17alpha-hydroxyprogesterone is prepared through hydrogenation via a cheap catalyst, namely raney nickel by taking the 6-methylene-17-alpha-hydroxyprogesterone as a raw material. According to the invention, a 6-position methyl group is obtained by introducing a formyl group and then conducting reducing and hydrogenating, the catalyst can be recycled and reused, and the method is friendly to environment, simple in process, high in yield and low in cost.

The invention provides medicine compositions containing 17-alpha hydroxyprogesterone and application of the medicine compositions, in particular to a medicine composition containing the active ingredient of 17-alpha hydroxyprogesterone, and a medicine composition containing active ingredients of the 17-alpha hydroxyprogesterone and glucocorticoid. Found by study, the 17-alpha hydroxyprogesterone can obviously reduce the number and infiltration of biologic neutrophil in blood and respiratory tract, the lung inflammation of neutrophilic granulocyte is inhibited, and respiratory tract and lung interleukin / proinflammatory cytokines re ainhibited; by singly applying the 17-alpha hydroxyprogesterone, or jointly applying the 17-alpha hydroxyprogesterone and the glucocorticoid, the inflammatory disease of neutrophil can be very effectively prevented and treated.

The invention provides a preparation method of 2,6-dibromo 17a-hydroxyproxyprogesterone. The method includes the steps that 17a-hydroxyproxyprogesterone is reacted with bromine in a first organic solvent and an acid environment to obtain the dibromination product 2,6-dibromo 17a-hydroxyproxyprogesterone by making 2 and 6 sites of a 17a-hydroxyproxyprogesterone molecule subjected to dibromination,wherein a ratio of the 17a-hydroxyproxyprogesterone to the bromine to acid is 1g to (1.2 to 1.8 g) to (0.1 to 0.4 g), and a ratio of the 17a-hydroxyproxyprogesterone to the first organic solvent is 1g to (2 to 15 ml). The invention further provides a preparation method of 1,6-didehydro-17a-hydroxyproxyprogesterone correspondingly. The preparation methods of the 2,6-dibromo 17a-hydroxyproxyprogesterone and the 1,6-didehydro 17a-hydroxyproxyprogesterone have the advantages of simple and convenient process operation, safe and environment-friendly production, low production cost and the like. Compared with traditional production methods, the method has high product yield, good quality, and can reduce the product production cost by 30% to 35%; the solvent used in the process can be recovered and recycled, which is economical and environmentally friendly at the same time, and is very beneficial to industrial production.

An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of:the conversion of cholesterol to pregnenolone;the conversion of pregnenolone to progesterone;the conversion of progesterone to 17alpha-hydroxyprogesterone;the conversion of 17alpha-hydroxyprogesterone to cortexolone;the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host.

The invention relates to the field of compound preparation, in particular to a preparation method of 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone. The method includes: taking 11alpha, 17alpha-dihydroxyprogesterone as the raw material, carrying out elimination reaction, esterification reaction, bromination epoxy reaction and fluorination reaction to synthesize a 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone crude product; and finally performing column chromatography to obtain the high purity target object 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone refined product. The invention mainly solves the problem that the existing technology is short of synthesis method of the product, the product can be used as a reference substance for quality control of flurogestone acetate, is more beneficial to control of the flurogestone acetate quality and improvement of the drug safety.

The present invention relates to a steroidal compound of 3-hydroxyprogesterone-21-(2',5'-dimethoxy)benzylidene-5-ene-20-one shown in structural formula I and preparation method thereof, a medicinal composition containing the compound, and the application of the compound in preparation of medicines for prevention and / or treatment of neurodegenerative diseases.

The invention provides a method and a kit for simultaneously detecting five steroid hormones and application of the method and the kit, and belongs to the technical field of steroid hormone detection. The method comprises the step of detecting a pretreated sample to be detected on the basis of LC-MS / MS (Liquid Chromatography-Mass Spectrometry / Mass Spectrometry). The pretreatment method is optimized, so that accurate detection of five steroid hormones including testosterone, androstenedione, 17alpha-hydroxyprogesterone, dihydrotestosterone and dehydroepiandrosterone sulfate is realized, and the method can be applied to detection items of important steroid hormones in clinical androstenemia. The real level of the real concentration of the five steroid hormones in the body of a subject can be given easily, clinical use or laboratory use is facilitated, and the method has important guiding significance on auxiliary diagnosis of hyperandrogenemia and polycystic ovarian syndrome and has high practical application value.

The invention relates to a method for preparing 11alpha, 17alpha-dyhydroxyl-pregn-1,4-diene-3,20-dione by taking 17alpha-hydroxyprogesterone as a starting material and through mixed one-step fermentation adopting aspergillus ochraceus and arthrobacter simplex.

The invention discloses a method for preparing 11alpha, 17alpha-hydroxyprogesterone by utilizing immobilized hydroxylase conversion, which is characterized in that 17alpha-hydroxyprogesterone is used as a substrate, the 11alpha, 17alpha -hydroxyprogesterone is prepared by utilizing the immobilized hydroxylase conversion, and the method comprises the following steps of: preparing a culture medium, culturing aspergillus ochraceus in the culture medium, inducing hydroxylase, preparing the immobilized hydroxylase, preparing a conversion system, converting a substrate, extracting and refining a product and the like. The method has the advantages that the feeding concentration is high, the substrate conversion rate is high, the conversion period is short, the product is easy to separate, and the immobilized hydroxylase can be repeatedly used. The feeding concentration of 17 alpha-hydroxyprogesterone in a single enzyme reaction is 40 g / L, the molar conversion rate can reach 93%, and meanwhile, the immobilized hydroxylase can be repeatedly recycled for more than three times. The preparation method is simple in operation process and relatively low in production cost, and has a relatively high industrial application prospect.

The invention provides an application of hydroxyprogesterone hexanoate in preparation of a drug for inhibiting cytokine storm, especially PBMC cytokine release caused by a CD28 antibody and / or a CD3 antibody. Experimental results show that hydroxyprogesterone hexanoate can inhibit release of multiple PBMC cytokines caused by the CD28 antibody and / or the CD3 antibody in a concentration-dependent manner, and is a potential drug for treating cytokine storm.

The invention relates to the field of screening of congenital adrenal hyperplasia, in particular to a method for simultaneously determining six related steroid hormones of CAH. The six related steroid hormones are 17 alpha-hydroxyprogesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol, cortisol and corticosterone; the determination method comprises the following steps: S1, respectively preparing a mixed internal standard product, a quality control product and a standard curve product; s2, preparing a sample extracting solution; s3, extracting and incubating a sample; s4, concentrating the redissolved sample; and S5, determining the reconstitution fluid by using a liquid chromatography tandem mass spectrometer, drawing a calibration curve, and calculating the concentrations of 17 alpha-hydroxyprogesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol, cortisol and corticosterone in the sample to be detected. The CAH screening specificity and the positive predicted value can be effectively improved. And the detected analyte contains corticosterone, so that 11-OHD and 21-OHD are more effectively distinguished in CAH screening, and the CAH screening efficiency is improved.

The invention discloses a slow-release oxytocic agent for artificially inducing grouper gonad development and maturation, ovulation and ejaculation. 10%, 75-95% cholesterol, 1-19% cellulose; 1-3% vegetable oil is added to the formula components, mixed evenly, and cylindrical pills are made with a special mold. The invention is used to bury the grouper in the body to induce the maturation of the gonads to achieve ovulation and sperm discharge, so as to meet the needs of the grouper artificial seedling industrialization and large-scale breeding for seedlings.