97 results about "Steroid drugs" patented technology

A biological dehydrogenation preparation method of steroid drug intermediate takes the formula (1) compound as a substrate, and adopts an arthrobacter simplex biological dehydrogenation method to obtain formula (2) compound; the special process comprises the following steps: smashing or dissolving the formula (1) compound with solvent, putting into a fermentation tank in which arthrobacter is cultivated for biotransformation, extracting, separating and refining, and drying to obtain dehydrogenated polymer, i.e. compound (2); and the dehydrogenation transformation rate can reach 70 to 90 percent.

The present invention relates (a) to new compounds represented by Formula I: wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, S represents a steroid subunit (steroid moiety) derived from steroid drug with anti-inflammatory activity and L represents a linker molecule linking M and S, (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals. Such compounds inhibit many cytokines and immune mediators involved in immune responses which cause inflammation, allergy, or alloimmunity, including without limitation IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM, and TNF-α. Importantly, anti-inflammatory steroids exert a direct anti-inflammatory effect through binding to the glucocorticosteroid receptor.

The invention provides a 3-sterone-Delta[1]-dehydrogenase. By constructing various expression vectors and converting relevant strains, the invention obtains various engineering strains such as non-3-sterone-Delta[1]-dehydrogenase activity strains or high 3-sterone-Delta[1]-dehydrogenase activity strains; the engineering strains can be adopted to selectively prepare androst-4-alkene-3, 17-diketone and 9Alpha-androst-4-alkene-3, 17-diketone or androst-1, 4-diene-3, 17-diketone and 3-ketone-1, 4-dienes steroid compounds. The engineering strains can greatly improve the production efficiency and product quality of the steroid medical production system, are beneficial for reducing the energy consumption of steroid drugs during the production process, improving the utilization ratio of the prodrugs and simplifying the production steps, reduce the production cost, have moderate reaction conditions and friendly environment, are suitable for wide generalization and application and have higher economic benefits and social benefits.

The invention discloses a method for preparing progesterone by taking 1,4-androstenedione as a raw material, which comprises the following steps: 1) dissolving 1,4-androstenedione into an organic solvent, adding the acid of trimethyl orthoformate or triethyl orthoformate, and introducing nitrogen to protect the 1,4-androstenedione to synthesize the enol ether of 1,4-androstenedione, namely 3-methoxy-androstane 3,5-diene-20-ketone; and 2) dispersing (1-methoxy ethyl)-triphenylphosphine salt in a reaction medium, an organic solvent, adding alkali at low temperature, performing a Wittig reaction of the 3-methoxy-androstane 3,5-diene-20-ketone synthesized in the step 1), and purifying and crystallizing to obtain progesterone. By adopting the 1,4-androstenedione as the raw material, the method solves the problem that of lack in raw materials for synthesizing steroid drugs such as progesterone, and improves the utilization rate of 1,4-androstenedione and the yield of progesterone; the preparation process is simple.

The invention discloses a Mucor circinelloides lusitanicus AY234877 strain which has the stereoselective hydroxylase activity, which is collected in the China general microbiological culture collection center on November 20, 2007, the collection number is CGMCC.NO.2256, and the invention is characterized in that the positions of 6 Beta, 7 Alpha, 11 Alpha and 14 Alpha of C21 and C19 steroid substrates can be carried out a hydroxylation. The invention further discloses a method for preparing the 6 Beta, 7 Alpha, 11 Alpha and 14 Alpha hydroxylated derivatives of the C21 and C19 steroids and aza steroids. The method has simple operation, low cost and better yield and stereoselectivity; furthermore, the invention does not cause environmental pollution. The strain can carry out the hydroxylation reaction of the C21 and C19 steroids and aza steroid compounds which have the structural characteristics of 4-en-3-one or 5-en-3-ol, and the obtained hydroxylated derivatives are the important intermediates for the synthesis of a plurality of steroid compounds. Compared with the steroid hydroxylation chemical synthesis, the method can simplify drug synthetic steps, reduce pollution, reduce cost and have important application value for promoting the development process of the steroid drug intermediates of China.

The invention belongs to the field of preparation of steroid drugs and particularly relates to a preparation method of hydrocortisone acetate. The preparation method comprises steps as follows: a bromohydroxy compound is synthesized from a compound C5 as a raw material through a bromohydroxy reaction, a crude hydrocortisone acetate product is produced through a debromination reaction, and finally, a refined hydrocortisone acetate product is obtained through refining, wherein alkali halide is added as a catalyst of the bromohydroxy reaction and a feeding mass ratio of the compound C5 to alkali halide is 1:(0.08-0.1). The preparation method of hydrocortisone acetate has the advantages as follows: alkali halide is adopted as the catalyst of the bromohydroxy reaction, so that the key of the problem that the reaction is incomplete in the bromohydroxy reaction process is solved, and one novel preparation method of hydrocortisone acetate with stable product quality and higher yield is provided.

The invention provides a method for preparing a steroid drug intermediate employing bioconversion phytosterol. The method comprises the following steps: 1) providing turbid liquid of phytosterol; 2) providing a resting cell of a microbial strain for converting the phytosterol into a steroid drug intermediate; 3) mixing the turbid liquid of the phytosterol with the resting cell, and adding beta-cyclodextrin or chemically modified beta-cyclodextrin to evenly mix, and cultivating to finish conversion; 4) centrifuging the conversion liquid obtained in the step 3), separating supernatant from thallus, separating to obtain the steroid drug intermediate from the supernatant by solvent extraction. By adopting the method provided by the invention, the sterol feeding concentration is improved, the target product quantity is increased, simple separation of the thallus, a cosolvent and a product is achieved when the conversion lasting time is shortened, repeated use of the thallus and the cosolvent for a plurality of times is achieved, the production cost is greatly saved, and the method is applicable to industrial production.

The invention provides a preparation method of androst-4-ene-6beta,19-epoxy-3,17-dione. The androst-4-ene-6beta,19-epoxy-3,17-dione is prepared from androst-5-ene-3alpha-hydroxyl-17-one through reactions in five steps, namely 3-site protection, epoxidation, epoxide ring-opening, 6,19-site cyclization / 3-site hydrolysis and oxidation-dehydration. By-product (waste) generated from a process of synthesizing a steroid drug is effectively utilized, so that environmental pollution is relieved, and the androst-4-ene-6beta,19-epoxy-3,17-dione, which serves as an important intermediate product and is required in the process of synthesizing the steroid drug, is obtained. The preparation method disclosed by the invention is high in yield and low in cost.

The purpose is to provide a compound which can overcomes the disadvantages of conventional steroid drugs and NSAID. It is found that specific epoxy monohydroxy forms of eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid which are independently represented by formulae [chemical formula 1], [chemical formula 5] and the like have an inhibitory activity on neutrophils. This compound can inhibit the invasion of neutrophils into tissues and the activation of neutrophils which are observed in acute inflammations.

A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis. An assay is provided for identifying steroid drugs that are likely to cause drug interaction if administered to a subject in therapeutic amounts. Transgenic animals are also provided which express human SXR, thereby serving as useful models for human response to various agents which potentially impact P450-dependent metabolic processes.

A catalytic hydrogenation preparation of high content beta - (citrostadienol ) sitosterol used in food, cosmetic and steroid drugs etc. is carried out by: mixing plant sterol materials, dissolving in organic solvent, catalytic hydrogenating with hydrogenated catalysts under normal temperature and pressure or at certain pressure, hydrogenising stigmasterol in mixed plant sterol to get beta -sitosterol, finally, obtaining liquid phase product with 60% - 75% content of beta -sitosterol and higher yields. The loss of sterol is bellow 10%. Its advantages include: operating simply and safely with simple equipment, low production cost, clean environment.

The invention discloses a new method for synthesizing steroid drug eplerenone. A surface cortisol as a byproduct of hydrocortisone is used as a raw material to oxide 17-side chain into ketone; 5, 6-double bond is introduced by 3-one protection; 7-ester group is introduced by cyaniding; 11-hydroxy is eliminated and 9,11-double bond is introduced; 17-ketone group is subjected to epoxidation, condensation and decarboxylation; and finally, the 9,11-double bond is epoxidated to produce the eplerenone. The method has raw materials with cheap prices and available sources, the easy control of process operation, high yield and low cost and is suitable for industrialized production.

The invention relates to the field of preparation of steroid drugs and an intermediate of the same, and in particular relates to a preparation method for prednisone acetate. The method comprises the steps of taking 11 alpha, 17 alpha-dyhydroxy Pregnene-1,4-diene-3,20-dione as an initial material, oxidizing to obtain 17 alpha-hydroxy Pregnene-1,4-diene-3,11,20-trione, and carrying out iodization reacting to obtain the prednisone acetate. The invention provides a novel oxidation technology more suitable for production of the intermediate of the prednisone acetate, the synthesis path has the characteristics of low cost and simple operation, environment pollution pressure can be greatly reduce, and the yield and quality of the prednisone acetate can reach a satisfactory level.

The invention provides a novel synthesizing method of a steroid drug eplerenone.According to the synthesizing method, 11-alpha-hydroxycarvenone serves as the starting material, and eplerenone is generated through a series of reactions such as addition, substitution, elimination, oxidation, esterification and epoxidation.According to the synthesizing method of eplerenone, the starting material is low in price and easy to purchase, operation is simple and easy to control, the yield is high, the cost is low, and the method is suitable for industrial production.

This invention provides a method for stably producing type II alveolar epithelial cells from pluripotent stem cells. Specifically, the invention relates to a method for producing type II alveolar epithelial cells from pluripotent stem cells comprising steps of: (1) culturing pluripotent stem cells in a medium containing activin A and a GSK3β inhibitor; (2) culturing the cells obtained in Step (1) in a medium containing a BMP inhibitor and a TGFβ inhibitor; (3) culturing the cells obtained in Step (2) in a medium containing BMP4, retinoic acid, and a GSK3β inhibitor; (4) culturing the ventral anterior foregut cells obtained in Step (3) in a medium containing a GSK3β inhibitor, FGF10, KGF, and a NOTCH signal inhibitor; and (5) subjecting the alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a medium containing a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF.

The invention belongs to the biotechnology field, and particularly relates to a method for converting a substrate 4-AD into 11alpha, 15alpha-diOH-4-AD through Gibberella intermedia CA3-1. The bacterial strain is preserved in the Common Microorganism Center of China Committee for Culture Collection of Microorganisms, the preservation number is CGMCC No. 4903. The 4-AD can be converted into 11alpha, 15alpha-diOH-4-AD through the Gibberella intermedia CA3-1; when the substrate feed concentration is 4 g / L, the 4-AD conversion rate reaches up to 99.3%, and the yield of the 11alpha, 15alpha-diOH-4-AD is 68.7%. The synthesis of the 11alpha, 15alpha-diOH-4-AD provides a more diversified precursor for research of steroid drugs and intermediates thereof, and the certain research value and market significance are achieved.

The invention provides a method for synthesizing 7,21-dyhydroxyl-20-methyl pregnane-4-alkene-3-ketone by microorganisms. Through a two-step fermentation method, one or more kinds of fermentation liquor including mucor circinelloides lusitanicus, acremonium strictum, mucor.racemosus and aspergillus fumigatus can be used for efficiently converting 4-HBC into 7 alpha-OH-4-HBC and 7beta-OH-4-HBC. Under a condition that the inventory of substrate 4-HBC is 10-20 g / L, a conversion rate is high, two products, including 7alpha and 7beta-hydroxy-4-HBC are separated from the product, and the total yieldof the product is 46.5% to 85.32%. The method disclosed by the invention is convenient in operation, low in cost and high in yield, and has good economic value, and a new method is provided for the development and the synthesis of steroid drugs.

The invention relates to a production method of a steroid drug intermediate, in particular to a method for preparing pregna-5-ene-3[beta], 21-diol by a resting cell method. The method comprises the steps of (1) 3-site protection of phytosterol, (2) transformation of resting cells, (3) extraction, (4) hydrolysis and (5) refining. The phytosterol is used as a raw material to produce the pregnene-5-ene-3[beta], 21-diol, the raw material is easy to obtain, and the production cost is reduced; functional group protection is carried out on 3-hydroxyl of the phytosterol by adopting a protective agent,the pregn-5-ene-3[beta], 21-diol can be directly prepared through hydrolysis after fermentation, few byproducts are generated, the yield is higher, a reaction route is shorter, and many reaction steps and post-treatment steps required in a traditional preparation method are omitted.

Steroid drug tibolone is a drug for treatment of functional disorder diseases in climacteric or postoperative menopausal women. According to the route, estra-3, 5-diene-3, 17beta-diacetate is adopted as the raw material to undergo bromine addition so as to complete alkene displacement and synthesize 6-dehydronandrolone acetate. The drug is one of the important pro-drugs of tibolone, and the yield is 85%. The 6-dehydronandrolone acetate steroid drug synthesis method provided by the invention has the advantages of simple and easy operation, and high yield.

The invention provides a high performance liquid chromatography method and application thereof. The method is characterized by carrying out component analysis of a steroid compound-containing mixture by a high performance liquid chromatography, wherein the high performance liquid chromatography adopts reversed high performance liquid chromatography and gradient elution, and mobile phases adopted by the gradient elution respectively are water and acetonitrile having the content of 95%. Through the high performance liquid chromatography method, the steroid compound-containing mixture (such as a mixture containing androstenedione and / or phytosterol) can be simultaneously analyzed. The high performance liquid chromatography method eliminates the interference factors, greatly shortens analysis time, has simple, reliable and accurate processes, and solves the existing problems of many operation steps, long analysis time and many interference factors. Therefore, the high performance liquid chromatography method provides an effective approach for steroid drug research and production process industrial production management.

The invention provides a non-stop production decolorization system based on the working condition of continuous production of steroid drugs, and relates to the technical field of steroid drug production. The non-stop production decolorization system sequentially comprises an activated carbon filtering and cleaning device, an activated carbon activating and drying device, an activated carbon smashing device and a plurality of reaction tanks; a filtering feeding hole is formed above the activated carbon filtering and cleaning device, a filtering carbon outlet and a filtering liquid outlet pipe are arranged below the activated carbon filtering and cleaning device, and a filtering mechanism is arranged inside the device; the activated carbon activating and drying device is used for preheatingactivated carbon discharged from the filtering carbon outlet, introducing steam to activate, and performing heating and drying; the activated carbon crushing device is used for crushing the dried activated carbon; a reaction tank feeding hole and a reaction tank feeding hole are formed above the reaction tank, and a reaction tank discharging hole is formed below the reaction tank; a color detectoris arranged on a pipeline of the filtering liquid outlet pipe, and unqualified liquid is detected to flow back into the reaction tank. The system is used in steroid drug production working conditions, decoloration treatment is carried out on intermediates, and centralized treatment and control without stopping production are achieved.

The invention relates to a preparation and pre-use treatment method for glycolonitrile with cyanide-containing tail gas as the raw material. According to the method, the cyanide-containing tail gas is introduced into multiple stages of reaction stills containing formaldehyde and a catalyst to be directly subjected to an addition reaction, and a glycolonitrile product with a certain concentration is obtained; after material transferring, the glycolonitrile product is stored under the effect of a stabilizer for use, and before use, the pH is regulated with base or weak base till the glycolonitrile product is neutral. The catalyst is one of basic compounds including Na2SO3, Na2CO3, NaHCO3 and NaOH, the mass concentration of formaldehyde is 35%-37%, the mol ratio of formaldehyde to the catalyst is 1:(0.001-0.05), and the reaction temperature is 5-20 DEG C. According to the method, HCN in industrial waste gas of a steroid drug is chemically absorbed through formaldehyde, the catalyst and the stabilizer, glycolonitrile is generated through the reaction and serves as a raw material for biological preparation of glycollic acid, and therefore the cyanide-containing tail gas is fully absorbed and utilized and prevented from being directly exhausted to the atmosphere and polluting the environment.

A composition for the transdermal administration of a steroid drug containing a therapeutically effective amount of the drug; an absorption promoter consisting essentially of a diethylene glycol ether and a sorbitan ester; and a pharmaceutically acceptable adhesive matrix.

The invention relates to a production method of steroid drug intermediates, in particular to a method for preparing pregna-5-ene-3beta,21-diol by cell growth. The method comprises the following steps:(1) 3-site protection on phytosterol; (2) transforming of growth cells; (3) extracting; (4) hydrolyzing; and (5) refining. The preparation method disclosed by the invention is relatively low in costand shorter in route, and omits a plurality of reaction steps and post-treatment steps. The shortening of the reaction route is also beneficial to the improvement of the reaction yield, and the intermediate loss is reduced. According to the method, the step of 3-site hydroxyl protection is adopted firstly, and growth cell biological fermentation reaction is carried out later, so that the solubility of the fermentation substrate in the fermentation liquor is directly increased, the fermentation is facilitated, the yield of the product can be increased, and the generation of impurities is reduced. The preparation method provided by the invention can also reduce the use of chemical reagents and is beneficial to environmental protection.

The invention relates to a method for synthesizing a steroid drug dydrogesterone (CAS: 152-62-5). The method comprises the following steps: starting from pregnenolone, carrying out allylic halogenation and elimination to obtain a Pregna-5, 7-dien-3-ol-20-one intermediate; carrying out illumination isomerization to obtain a key intermediate 9 beta, 10 alpha-Pregna-5, 7-dien-3-ol-20-one; then carrying out Oppenauer oxidation (Oppenauer oxidation) to obtain 7-Dehydro-9beta, 10 alpha-progesterone, and finally, carrying out olefin shift isomerization under the action of acid to obtain the final product 6-Dehydro-9beta, 10 alpha-progesterone (a crude drug of dydrogesterone). The method is economical in steps and comprises four conversion steps; the total yield is as high as 16.4%; the raw materials are cheap and easy to obtain, the whole process route is green and safe, the bulk drugs are high in quality, the purity can reach 99.5% or above, and the method is suitable for industrial production.

Antibodies targeting the dysadherin subunit of the human Na,K-ATPase signaling complex that are covalently linked via a stable linker to steroid drugs that bind the alpha subunit of that complex are useful in the treatment of cancer.

A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis. An assay is provided for identifying steroid drugs that are likely to cause drug interaction if administered to a subject in therapeutic amounts. Transgenic animals are also provided which express human SXR, thereby serving as useful models for human response to various agents which potentially impact P450-dependent metabolic processes. Also provided are expression systems and expression vectors having SXR receptors and the like operably linked to target genes of interest.