41 results about "Epiandrosterone" patented technology

The application belongs to the technical field of medicine synthesis, and particularly relates to a steroid and 3,4 dihydropyrrole pyrazinone derivative and a synthesis method and application thereof. The derivative has a chemical structure as described in formula (I) or formula (II). The application first proposes a series of novel steroid and 3,4 dihydropyrrole pyrazinone derivatives. In addition, the application also proposes a synthesis method of the steroid and 3,4 dihydropyrrole pyrazinone derivative. The steroid and 3,4 dihydropyrrole pyrazinone derivative is obtained through a series of reactions based on dehydroepiandrosterone. The product prepared by the synthesis method has high yield and is easy to separate, and is the optimal method for preparing the steroid and 3,4 dihydropyrrole pyrazinone derivative. The steroid and 3,4 dihydropyrrole pyrazinone derivative provided by the application is confirmed by biological determination to have good toxic killing activity on aphids, spider mites and oriental armyworm insects, and can be applied to plant pest control.

The invention relates to an industrial preparation method of an intermediate 5alpha-androstane-2-ene-17 ketone, the intermediate is a rocuronium bromide intermediate, and the method comprises the following steps: taking epiandrosterone as a starting material, and reacting with paratoluensulfonyl chloride to obtain a compound I; and carrying out elimination reaction on the compound I in organic alkali or a DBU catalyst to obtain the compound 5 alpha-androstane-2-ene-17 ketone. The method is good in elimination reaction selectivity, high in yield, good in quality, low in cost, mild in reaction condition, short in production period, recyclable in reaction solvent and green and environment-friendly in production process, and a single impurity of the product is less than 0.3%.

The present disclosure relates to the use of cortisol, cortisone, cortisone acetate, hydrocortisone, fludrocortisone, prednisolone, prednisone, methylprednisolone, Dehydroepiandrosterone (DHEA), dexamethasone, betamethasone, adrenocorticotropic hormone (ACTH), ganaxolone, tetracosactide or combinations thereof for preventing and / or reducing the risk of Sudden Unexpected Death in Epilepsy (SUDEP). The disclosure further provides pharmaceutical compositions and methods for preventing and / or reducing the risk of SUDEP, particularly in Dravet Syndrome patients.

The invention belongs to the technical field of medical animal disease model modeling, and particularly discloses a dehydroepiandrosterone-induced mouse polycystic ovarian syndrome model under bisphenol A low-dose exposure, specifically, a preparation method of the model comprises the following steps: continuously injecting a mouse for 21 days according to the injection amount of dehydroepiandrosterone of 6mg / 100g; the method comprises the following steps: carrying out intragastric administration on a mouse by using 10 mg / kg of bisphenol A on the 15th day of injection of dehydroepiandrosterone, and continuously carrying out intragastric administration on the mouse for 7 days to obtain the polycystic ovarian syndrome model of the mouse at the childbearing age. According to the mouse model obtained by DHEA modeling at the early stage of adolescence and BPA exposure modeling at the late stage of adolescence, the disordered mood cycle, obesity and high T level are obviously changed; and the human PCOS disease environment and clinical phenotype can be truly simulated.

The invention discloses a synthesis method of HE3286, belongs to the technical field of medicine preparation, and provides a brand-new synthesis method of HE3286, according to the method, dehydroepiandrosterone acetate is used as a raw material, and high-purity HE3286 is efficiently prepared through only five steps of ethynylation, diacetylation, oxidation, reduction and deprotection. The HE3286 synthesis method provided by the invention has the characteristics of cheap and easily available reagents, simplicity and safety in operation, low cost, no pollution and easiness in large-scale industrial production, and has a wide application prospect.

The invention relates to a recombinant strain for producing dehydroepiandrosterone and a construction method and application thereof, and belongs to the technical field of biology. According to the genetically engineered bacterium obtained by reducing or eliminating the enzymatic activity of NAD (P) dependent oxidase in an original strain, the DHEA can be directly produced through one-step biological fermentation by taking phytosterol or cholesterol as a substrate. In the genetically engineered bacterium, the activity of sterol-like-isomerase is further reduced or eliminated, and the activities of oxidoreductase, dehydrogenase and ACP-reductase are further reduced or eliminated in a superposed manner, so that the yield of DHEA can be accumulated step by step, the DHEA finally becomes a main product, meanwhile, the proportion of by-products 4-AD and androstenediol is reduced, and the yield of DHEA is increased. The purity is improved while the yield of the DHEA is improved, and subsequent treatment and application are facilitated.

The present invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to epiandrosterone pyrazole derivatives, their synthesis methods and applications. The epiandrosterone pyrazole derivatives have a chemical structure represented by the general formula (1), wherein R is an alkyl group or an aromatic ring-containing group. The alkyl group is an aliphatic chain or a cycloalkane, and the aromatic ring-containing group is a phenyl group or a substituted phenyl group. The synthesis method of the epiandrosterone pyrazole derivatives uses epiandrosterone as a basic raw material and obtains the epiandrosterone pyrazole derivatives of the present invention through a series of different reactions. The epiandrosterone pyrazole derivatives disclosed in the present invention are a series of brand-new compounds, which are proposed for the first time. The synthesis method has a high preparation yield, and the obtained product is easy to separate. It is confirmed by biological assays that the epiandrosterone pyrazole derivatives exhibit good insecticidal activity against pests such as aphids, oriental armyworms, diamondback moths and whiteflies, and can be applied to the control of plant pests.

The invention discloses a method for detecting cortisol, testosterone and dehydroepiandrosterone in saliva, and belongs to the field of biological medicine. The technical problem to be solved is to provide a method for accurately detecting cortisol, testosterone and dehydroepiandrosterone in saliva. According to the technical scheme, the method for detecting cortisol, testosterone and dehydroepiandrosterone in saliva is characterized in that a magnetic bead method is adopted for sample pretreatment, a to-be-detected sample is obtained through magnetic bead activation, balancing, sample loading, leaching, elution and nitrogen blowing redissolution, and the to-be-detected sample is detected through a liquid chromatography-tandem mass spectrometry method. The contents of cortisol, testosterone and dehydroepiandrosterone in the sample to be detected are obtained. The detection method is accurate and reliable in detection result, simple, convenient and efficient to operate, and meets industrial practical requirements.

The invention relates to the technical field of organic synthesis of steroid compounds, in particular to a preparation method of androstane-4-ene-3, 6, 17-triketone. Dehydroepiandrosterone acetate is used as an initial raw material to prepare androstane-4-ene-3, 6, 17-triketone through four steps of reactions including chlorohydrination, hydrolysis, oxidation and elimination, the yield and purity of androstane-4-ene-3, 6, 17-triketone are improved, 4-AD impurities are not generated, the total yield of a route reaches 80%, and the purity is larger than or equal to 98.0%; and the preparation process does not involve the use of dangerous chemicals and environment-polluting chromium oxidants, and is suitable for industrial production.

The invention provides a method for preparing dehydroepiandrosterone, which comprises the following steps: S1, taking 4-androstene-3, 17-diketone as a raw material to react to generate 5-androstene-3, 17-diketone; s2, sodium acetate is dissolved in a buffer system, ascorbyl palmitate, L-glutathione, the 5-androstene-3, 17-diketone, ketoreductase, coenzyme and a coenzyme regeneration system are sequentially added for a reaction, and dehydroepiandrosterone is obtained. According to the invention, the ascorbyl palmitate, the L-glutathione and the sodium acetate cooperate to inhibit the side reaction of an intermediate product, active oxygen and the like to generate impurities, so that the purity and the yield of the dehydroepiandrosterone are improved, the purity of the final product dehydroepiandrosterone is as high as 99%, and the yield is as high as 95%.

The present invention relates to the technical field of biology, and relates to a recombinant strain for producing dehydroepiandrosterone (DHEA), a construction method therefor, and a use thereof. By means of genetically engineered bacteria obtained by reducing or eliminating the enzymatic activity of NAD(P)-dependent oxidase in a starting strain, direct production of DHEA by means of one-step biological fermentation using phytosterol or cholesterol as a substrate can be achieved. By further reducing or eliminating the activity of steroid Δ-isomerase in the genetically engineered bacteria and further reducing or eliminating the activity of oxidoreductase, dehydrogenase and ACP-reductase in a superimposed manner, the yield of DHEA can be accumulated step by step, finally making DHEA become a principal product while reducing the proportions of the by-products 4-AD and androstenediol, thereby improving purity while improving the yield of DHEA, facilitating subsequent treatment and use.

Disclosed herein are compounds and pharmaceutical compositions useful for treating, preventing, reducing, or ameliorating diseases or conditions associated with neurodegenerative disorders. Without being bound by theory, the disclosed compounds and compositions are believed to selectively target tropomyosin receptor kinase A (TrkA) receptor-mediated pro-survival signaling pathways or the nerve growth factor (NGF) or the neurosteroid dehydroepiandrosterone (DHEA) and may prevent, treat, reduce, or ameliorate neurodegeneration.

The invention relates to the technical field of medicine synthesis, in particular to C3 and C20 N-containing pregnane type steroid alkaloid derivatives as well as a preparation method and application thereof. A pregnane type steroid alkaloid skeleton in Miao medicine tri-silver is used as a template, a steroid compound epiandrosterone is used as a raw material, C3-site and C20-site keto compounds are obtained through Wittig alkylenation reaction and oxidation, and the C3-site and C20-site keto compounds are subjected to continuous reductive amination reaction to obtain a series of pregnane type steroid alkaloid derivatives containing N at C3 site and C20 site simultaneously. The C3 and C20 N-containing pregnane type steroid alkaloid derivatives provided by the invention have remarkable anti-inflammatory and anti-gastric ulcer activity, and a scientific basis is provided for searching novel anti-inflammatory and anti-gastric ulcer lead compounds with high selectivity and safety and developing novel anti-inflammatory and anti-gastric ulcer medicines.

The invention discloses a colletotrichum linum P450 enzyme mutant and application thereof, the mutant is obtained by mutating 121st aspartic acid of an amino acid sequence of P450 enzyme CYP68J derived from a colletotrichum linum ST-1 strain into histidine, and the amino acid sequence is shown as SEQ ID NO: 1. Compared with a wild type P450 enzyme, the P450 enzyme mutant disclosed by the invention has the advantages that dehydroepiandrosterone can be efficiently converted into 7 alpha-hydroxy-dehydroepiandrosterone, and the ratio of 7 alpha-hydroxy-dehydroepiandrosterone to 7 alpha, 15 alpha-dihydroxy-dehydroepiandrosterone in a hydroxylation product can be increased from about 4: 5 to about 14: 1; an important way is provided for the biological conversion of the 7alpha-hydroxyl-dehydroepiandrosterone, and the method has important significance on the industrial production of the 7alpha-hydroxyl-dehydroepiandrosterone.

This invention discloses a method for preparing 7α,15α-dihydroxydehydroepiandrosterone (DHEA). The method comprises the following steps: DHEA is fed into a liquid culture medium containing *Colletotrichum lini* to convert the DHEA into 7α,15α-dihydroxydehydroepiandrosterone. The *Colletotrichum lini* liquid culture medium also contains cyclodextrin and its derivatives, and Tween. The conversion step includes: first, a low-temperature conversion, followed by a medium-temperature conversion; the low-temperature conversion conditions are: a conversion temperature of 15–20°C, preferably 16°C; the medium-temperature conversion conditions are: a conversion temperature of 28°C. Furthermore, by adding cyclodextrin and its derivatives and Tween, the feed amount of 7α,15α-dihydroxydehydroepiandrosterone prepared in this invention can be increased from 15 g / L to 30 g / L, and the relative conversion rate can reach 90%.

The present invention relates to a compound suitable for external use and a pharmaceutical composition, the pharmaceutical composition contains 17 beta-dammarin B or a pharmaceutically acceptable salt, a raceme, a stereoisomer, an enantiomer, a diastereoisomer, a tautomer, a metabolite, a solvate and a pro-drug thereof as active ingredients, and the pharmaceutical composition can treat skin cancer or precancerous lesions thereof, such as cancer, cancer, cancer and the like. Especially, the traditional Chinese medicine composition has a good treatment effect on skin squamous cell carcinoma and basal skin cancer.

This invention proposes a method for preparing dehydroepiandrosterone (DHEA), comprising the following steps: S1, dissolving 4-androstenedione in acetic anhydride to obtain a first material, which is then pumped separately into an acetylation microchannel reactor with quaternized GO-phosphotungstic acid catalyst supported on the inner wall for reaction with acetyl chloride; S2, mixing triethyl orthoformate with anhydrous ethanol to obtain a second material, which is then pumped separately into a ketal microchannel reactor with niobium oxide / γ-CD-phosphotungstic acid catalyst supported on the inner wall of the ketal microchannel reactor; S3, dehydrating the effluent from step S2 and adjusting the pH to 7-8, then pumping separately into a reduction microchannel reactor with an ethanol solution containing sodium borohydride for reduction reaction; S4, adding hydrochloric acid to the effluent from step S3 and adjusting the pH to 2-3 to obtain a hydrolysate; evaporating the solvent from the hydrolysate, filtering and drying to obtain DHEA. The supported heteropolyacid composite membrane used in this invention exhibits high catalytic efficiency, high yield, and excellent quality.

The present invention provides a method for preparing dehydroepiandrosterone by a chemical-enzymatic method, belonging to the technical field of pharmaceutical compounds. In the present invention, water, glacial acetic acid and sodium D-ascorbate are mixed and then tert-butanol, a strong base catalyst and 4-androstenedione are sequentially added for reaction to obtain 5-androstenedione; a phosphate buffer system is obtained by mixing tert-butanol with a phosphate buffer solution; 5-androstenedione, magnesium chloride, ketoreductase, coenzyme and a coenzyme regeneration system are added to the phosphate buffer system for an enzymatic reaction, and dehydroepiandrosterone is obtained. The target product is synthesized in two steps by the combined chemical-enzymatic method in the present invention, and the yield of the product is as high as 95%, and the purity is above 99%. The synthesis method of the present invention effectively solves the problems of complex chemical process and difficult post-treatment of biological method, not only simplifies the process, but also improves the yield and purity of DHEA, and can realize large-scale production.

The invention relates to a preparation method of a key antigen marker for dehydroepiandrosterone sulfate chemiluminescence detection and application of the key antigen marker in a detection reagent. Dehydroepiandrosterone which is easy to obtain, low in price and similar to dehydroepiandrosterone sulfate (DHEA-S) in chemical structure is selected as a starting material of a competitive antigen, an optimal synthesis process route is designed according to a designed target product by considering a cost factor, separation and purification difficulty and a later amplification production factor, and the dehydroepiandrosterone is synthesized through a simple reaction. The preparation method comprises the following steps: preparing an epiandrosterone derivative, directly coupling the epiandrosterone derivative with acridine salt, and purifying to obtain the epiandrosterone derivative which can be used as a key competitive antigen raw material of a DHEA-S magnetic particle chemiluminescence immunoassay reagent. The detection reagent and the raw materials are easy to obtain, the preparation is simple, the specificity is good, the result is accurate, the cost is low, and the scale detection of the dehydroepiandrosterone sulfate is met.

The invention provides a kit for simultaneously detecting six steroid hormones and application of the kit. The steroid hormones comprise testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, dihydrotestosterone and 17alpha-hydroxyprogesterone. The kit comprises extract liquor, a mobile phase additive and a standard quality control product. The kit provided by the invention can be used for simultaneously detecting testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, dihydrotestosterone and 17alpha-hydroxyprogesterone, and has the advantages of high accuracy, low quantitation limit and wide detection range.

The application discloses a kind of structural diversity steroidal ketone derivatives and its chemical-microorganism catalytic combined preparation method and application, belong to biological medicine preparation technical field.The structural diversity steroidal ketone derivatives described in the application include four big types of steroidal derivatives, such as sterol conversion into steroidal ketone derivative, pyrimidine derivative, thiazoline derivative or bis-hydrazone derivative.Firstly, four structural types of sterol derivatives are prepared by chemical method with dehydroepiandrosterone as raw material;Secondly, microbial cell catalysis is used, i.e., new mycobacterium aurum strain is used to catalyze oxidation of sterol and isomerization to obtain novel steroidal ketone derivatives.The chemical-microorganism cell catalytic combined method of the application can realize the preparation of compounds that cannot be obtained by partial chemical method, and the microbial cell catalysis step has mild conditions, simple separation and extraction process, and is environment-friendly, which provides a new strategy for constructing novel steroidal derivative molecular library.

A chemoenzymatic method for synthesizing steroid HE3286 is provided, comprising: screening cytochrome P450 mutant LG-23 capable of catalyzing 7β-hydroxylation of dehydroepiandrosterone; enzymatically converting dehydroepiandrosterone to 7β-hydroxy-dehydroepiandrosterone using the P450 BM3 mutant enzyme; and chemically performing alkynylation at the C17th position carbonyl group to generate steroid HE3286. The steroid HE3286 synthesis method not only features simplified synthetic steps and high catalytic selectivity, but also offers mild reaction conditions, low cost, and environmentally friendly efficiency. This approach holds significant application value for advancing the development of steroid pharmaceuticals.

A combination of medications and medication doses is disclosed whereby age-related changes in systemic inflammation, cancer risk, heart disease risk, CD38 expression, hair color, thymotrophic hormones, immune cell populations, the CD4 / CD8 cell ratio, bone marrow density, thymus structure, kidney function, and epigenetic age can be reversed in humans. Surprisingly, agents that accelerate the growth of cells reduce cancer risk, agents that intensify immune responses attenuate age-related inflammation, agents with no prior connection to hair color reverse age-related hair whitening, and a combination of agents that induces IGF-1, a hormone previously thought to drive systemic aging, results in a reversal of systemic aging as documented by an epigenetic clock. Medication combinations useful in the present invention include human growth hormone (GH) or GH releasers, dehydroepiandrosterone (DHEA), and metformin.

The present invention discloses a novel alkaloid derivative, its synthesis method and application. Based on the active pregnane-type alkaloid skeleton structure in the Miao medicine "Sanyangyin", using epiandrosterone as a raw material, a series of C20-oxime pregnane-type alkaloid derivatives are obtained through reactions such as Wittig reaction, reduction reaction, Corey oxidation, reductive amination, and N-alkylation. This method has a simple and efficient preparation process and mild reaction conditions. The synthesized C20-oxime pregnane-type alkaloid derivatives have excellent anti-tumor activity and anti-inflammatory properties and can be used in anti-tumor and anti-inflammatory drugs. It provides a scientific basis for the new drug development and application of novel anti-tumor and anti-inflammatory pregnane-type alkaloids.

The invention belongs to the technical field of chemical synthesis, and particularly relates to an asymmetric synthesis method of an alpha-chiral ester compound. Comprising the following step: in a solvent, performing asymmetric alpha-protonation and esterification reaction on alpha-alkyl-alpha, beta-unsaturated aldehyde and alcohol as shown in a formula II in the presence of a chiral N-heterocyclic carbene catalyst, alkali and protonic acid to obtain the alpha-chiral ester compound. The invention develops a redox esterification reaction based on chiral N-heterocyclic carbene catalysis, so that the redox esterification reaction can be efficiently suitable for various alpha-alkyl alpha, beta-olefine aldehydes from simple to high steric hindrance and from chain to polycyclic; the catalytic strategy can be directly applied to later directional esterification modification of important natural product derivatives such as oestrone and epiandrosterone, and a powerful tool is provided for research and development of new drugs.

The invention provides a method for synthesizing dehydroepiandrosterone through chemical-multienzyme coupling catalysis, and belongs to the technical field of pharmaceutical preparations with specific therapeutic activity. The method comprises the following steps: by taking 4-androstenedione as a substrate, carrying out esterification to synthesize 3-acetoxyandrostane-3, 5-diene-17-ketone; adding a lipolytic enzyme, and catalyzing the 3-acetoxyandrostane-3, 5-diene-17-ketone to synthesize the 5-androstenedione; ketoreductase and glucose dehydrogenase are added, and 5-androstenedione is catalyzed through double-enzyme coupling to synthesize DHEA. The method provided by the invention can realize efficient synthesis of DHEA.

The invention belongs to the field of pharmaceutical compositions, and relates to a composition containing dehydroepiandrosterone, a preparation and a preparation method thereof. The composition containing dehydroepiandrosterone provided by the invention still has stable particle size distribution after standing for 30 days, and is not layered and the particle size distribution is not obviously changed after standing for a long time; after being prepared into a pharmaceutical preparation, the dehydroepiandrosterone derivative has good drug encapsulation efficiency and stable dehydroepiandrosterone content, and has a wide application prospect.

The invention relates to a contraceptive kit comprising: · 23 to 25 first oral dosage units, each first oral dosage unit containing a combination of 100-165 µg of levonorgestrel, 20-40 µg of ethinylestradiol and 40-120 mg of dehydroepiandrosterone; and · 3 to 5 second oral dosage units, each second oral dosage unit containing 40-120 mg of dehydroepiandrosterone, no progestogen and no estrogen; wherein the sum of the number of first oral dosage unit and the number of second oral dosage units in the contraceptive kit equals 28. The contraceptive kit of the invention provides high contraceptive reliability and produces less undesirable side-effects than commercially available combined oral contraceptives.

The invention discloses a recombinant keto reductase and application thereof in dehydroepiandrosterone synthesis, the recombinant keto reductase is based on Crocecoccus esterase sourced 3-keto reductase, the recombinant keto reductase is constructed by modifying an active pocket of an enzyme through a genetic engineering technology and computer-aided design, the recombinant keto reductase has outstanding enzymatic activity and stability, and the recombinant keto reductase can be applied to dehydroepiandrosterone synthesis. And a better choice is provided for preparing medicines such as dehydroepiandrosterone and the like by enzyme catalysis keto reduction.

The invention relates to a method for synthesizing steroid HE3286 by combining an enzyme method and a chemical method, which comprises the following steps: screening cytochrome P450 mutant LG-23 for catalyzing dehydroepiandrosterone 7beta-hydroxylation, catalyzing dehydroepiandrosterone by using P450BM3 mutant enzyme to generate 7beta-hydroxydehydroepiandrosterone, and then carrying out ethynylation reaction of 17-position carbonyl by using the chemical method to generate the steroid HE3286. The method for synthesizing HE3286 is simple in synthesis step, high in catalytic selectivity, capable of reducing by-products and improving the yield, mild in reaction condition, low in cost, green, environmentally friendly and efficient, and has important application value for promoting the development process of steroid drugs in China.